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  • 1.
    Algilani, Samal
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Östlund-Lagerström, Lina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kihlgren, Annica
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Blomberg, Karin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Schoultz, Ida
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Exploring the concept of optimal functionality in old age2014In: Journal of Multidisciplinary Healthcare, ISSN 1178-2390, E-ISSN 1178-2390, Vol. 7, p. 69-79Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Aging is characterized by loss of function and represents a perspective that puts the focus on the negative aspects of aging. Thus, it is fundamental to shift the focus from loss of function to maintaining good health and personal satisfaction through life; in other words, to promote optimal functionality at a level appropriate for older adults. However, it is not yet known what constitutes optimal functionality from the older adult's own perspective.

    OBJECTIVE: To explore the concept of optimal functionality in old age from the older adult's perspective (ie, people over 65 years of age) in industrialized Western countries.

    METHODS: We undertook a scoping review and searched two electronic databases (PubMed and the Cumulative Index to Nursing and Allied Health Literature [CINAHL]) from January 2002 to July 2013 for scientific studies, using the key search term personal satisfaction. In total, 25 scientific studies were analyzed.

    RESULTS: Only six of the included articles applied a qualitative methodology. By analyzing the results of these articles, three major themes were identified as cornerstones in the concept of optimal functionality at old age: 1) self-related factors (eg, mental well-being); 2) body-related factors (eg, physical well-being); and 3) external factors equal to demographic and environmental factors.

    CONCLUSION: There is a lack of qualitative studies in the current literature, and hence of what constitutes optimal functionality from the older adult's perspective. The results outlined in this review identify three cornerstones (self-related factors, body-related factors, and external factors) of what constitutes optimal functionality at old age. However, it is vital that these findings are taken further and are evaluated through qualitative studies to reflect older adults' opinions.

  • 2.
    Algilani, Samal
    et al.
    Örebro University, School of Health Sciences.
    Östlund-Lagerström, Lina
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Brummer, Robert J.
    Örebro University, School of Medical Sciences.
    Kihlgren, Annica
    Örebro University, School of Health Sciences.
    Increasing the qualitative understanding of optimal functionality in older adults: a focus group based study2016In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 16, no 1, article id 70Article in journal (Refereed)
    Abstract [en]

    Background: Decreased independence and loss of functional ability are issues regarded as inevitably connected to old age. This ageism may have negative influences on older adults' beliefs about aging, making it difficult for them to focus on their current ability to maintain a good health. It is therefore important to change focus towards promoting Optimal Functionality (OF). OF is a concept putting the older adult's perspective on health and function in focus, however, the concept is still under development. Hence, the aim was to extend the concept of optimal functionality in various groups of older adults.

    Methods: A qualitative study was conducted based on focus group discussions (FGD). In total 6 FGDs were performed, including 37 older adults from three different groups: group 1) senior athletes, group 2) free living older adults, group 3) older adults living in senior living homes. All data was transcribed verbatim and analyzed following the process of deductive content analysis.

    Results: The principal outcome of the analysis was "to function as optimally as you possibly can", which was perceived as the core of the concept. Further, the concept of OF was described as multifactorial and several new factors could be added to the original model of OF. Additionally the findings of the study support that all three cornerstones comprising OF have to occur simultaneously in order for the older adult to function as optimal as possible.

    Conclusions: OF is a multifaceted and subjective concept, which should be individually defined by the older adult. This study further makes evident that older adults as a group are heterogeneous in terms of their preferences and views on health and should thus be approached as such in the health care setting. Therefore it is important to promote an individualized approach as a base when caring for older adults.

  • 3.
    Boersma, Katja
    et al.
    Örebro University, School of Law, Psychology and Social Work.
    Ljótsson, Brjánn
    Deptartment of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Edebol-Carlman, Hanna
    Schrooten, Martien
    Örebro University, School of Law, Psychology and Social Work.
    Linton, Steven J.
    Örebro University, School of Law, Psychology and Social Work.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences. Department of gastroenterology, Örebro university hospital, Örebro, Sweden.
    Exposure-based cognitive behavioral therapy for irritable bowel syndrome: A single-case experimental design across 13 subjects2016In: Cognitive Behaviour Therapy, ISSN 1650-6073, E-ISSN 1651-2316, Vol. 45, no 6, p. 415-430Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a highly prevalent disorder with a significant impact on quality of life. The presence of psychological symptoms in IBS patients such as catastrophic worry and behavioral avoidance suggests the possible efficacy of cognitive behavioral interventions. Exposure-based cognitive behavioral therapy (CBT) has proven to be a promising approach but has only been investigated in a few studies and mainly via the Internet. Therefore, the aims of this study were to extend and replicate previous findings and to evaluate whether an individual, face-to-face, exposure-based CBT leads to improvement in gastrointestinal symptoms, pain catastrophizing, avoidance behavior and quality of life in IBS patients. Thirteen patients with IBS according to Rome III criteria participated in a single-case experimental study using a five-week baseline and a subsequent twelve-session intervention phase focusing on psycho-education, mindfulness and in vivo exposure. Standardized measurement of gastrointestinal symptoms, pain catastrophizing, avoidance behavior and quality of life was conducted weekly during baseline as well as intervention phase and at six-month follow-up. Results showed that over 70% of patients improved significantly on gastrointestinal symptoms, pain catastrophizing, and quality of life. Effects on avoidance behavior were modest. These results strengthen and extend earlier findings and provide further support for the efficacy of exposure-based strategies for IBS.

  • 4.
    Bron, Peter A.
    et al.
    NIZO Food Research, Ede, The Netherlands; BE-Basic Foundation, The Netherlands, Delft, The Netherlands.
    Kleerebezem, Michiel
    Host Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands.
    Brummer, Robert-Jan
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Cani, Patrice D.
    Metabolism and Nutrition Research Group, WELBIO – Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
    Mercenier, Annick
    Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
    MacDonald, Thomas T.
    Barts and The London school of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.
    Garcia-Ródenas, Clara L
    Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
    Wells, Jerry M.
    Host Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands.
    Can probiotics modulate human disease by impacting intestinal barrier function?2017In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 117, no 1, p. 93-107Article, review/survey (Refereed)
    Abstract [en]

    Intestinal barrier integrity is a prerequisite for homeostasis of mucosal function, which is balanced to maximise absorptive capacity, while maintaining efficient defensive reactions against chemical and microbial challenges. Evidence is mounting that disruption of epithelial barrier integrity is one of the major aetiological factors associated with several gastrointestinal diseases, including infection by pathogens, obesity and diabetes, necrotising enterocolitis, irritable bowel syndrome and inflammatory bowel disease. The notion that specific probiotic bacterial strains can affect barrier integrity fuelled research in which in vitro cell lines, animal models and clinical trials are used to assess whether probiotics can revert the diseased state back to homeostasis and health. This review catalogues and categorises the lines of evidence available in literature for the role of probiotics in epithelial integrity and, consequently, their beneficial effect for the reduction of gastrointestinal disease symptoms.

  • 5. Dullemeijer, C.
    et al.
    Verhoef, P.
    Brouwer, I. A.
    Kok, F. J.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    Durga, J.
    Plasma very long-chain n-3 polyunsaturated fatty acids and age-related hearing loss in older adults2010In: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 14, no 5, p. 347-351Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Age-related hearing loss is a common social and health problem in the older adult population. Up until now, very little scientific attention has been given to the potential role of fatty acids in age-related hearing loss. In this study we investigated whether plasma very long-chain n-3 polyunsaturated fatty acids (PUFAs) are associated with age-related hearing loss over three years.

    DESIGN: Cross-sectional and 3-year longitudinal analyses.

    SETTING: Wageningen, the Netherlands.

    PARTICIPANTS: 720 men and postmenopausal women (50-70 years of age) without middle ear dysfunction or unilateral hearing loss.

    MEASUREMENTS: Fatty acid proportions were measured in plasma cholesteryl esters. Hearing thresholds (in decibels, dB) at baseline and after three years were measured with pure-tone audiometry. Hearing loss was calculated as the increase in mean hearing thresholds in the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies over three years.

    RESULTS: Subjects in the highest quartile of plasma very long-chain n-3 PUFA had less hearing loss in the low frequencies over three years than subjects in the lowest quartile (p < 0.01, ANCOVA, difference in mean adjusted hearing thresholds= -1.2 dB). There were no significant differences between the quartiles of plasma very long-chain n-3 PUFA in hearing loss in the high frequencies (p=0.49, ANCOVA). These associations are adjusted for baseline mean hearing thresholds, age, sex, level of education and alcohol consumption.

    CONCLUSION: This study is the first to show an inverse association between plasma very long-chain n-3 PUFAs and age-related hearing loss. These results are encouraging, but require confirmation from future studies.

  • 6. Dullemeijer, Carla
    et al.
    Zock, Peter L.
    Coronel, Ruben
    Den Ruijter, Hester M.
    Katan, Martijn B.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    Kok, Frans J.
    Beekman, Jet
    Brouwer, Ingeborg A.
    Differences in fatty acid composition between cerebral brain lobes in juvenile pigs after fish oil feeding2008In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 100, no 4, p. 794-800Article in journal (Refereed)
    Abstract [en]

    Very long-chain n-3 PUFA from fish are suggested to play a role in the development of the brain. Fish oil feeding results in higher proportions of n-3 PUFA in the brains of newborn piglets. However, the effect of fish oil on the fatty acid composition of specific cerebral brain lobes in juvenile pigs is largely uninvestigated. This study examined the effect of a fish oil diet on the fatty acid composition of the frontal, parietal, temporal and occipital brain lobes in juvenile pigs (7 weeks old). Pigs were randomly allocated to a semipurified pig diet containing either 4% (w/w) fish oil (n 19) or 4% (w/w) high-oleic acid sunflower oil (HOSF diet, n 18) for a period of 8 weeks. The fish oil diet resulted in significantly higher proportions (%) of DHA in the frontal (10.6 (SD1.2)), parietal (10.2 (SD1.5)) and occipital brain lobes (9.9 (SD 1.3)), but not in the temporal lobe (7.7 (SD1.6)), compared with pigs fed the HOSF diet (frontal lobe, 7.5 (SD1.0); parietal lobe, 8.1 (SD 1.3); occipital lobe, 7.3 (SD1.2), temporal lobe, 6.6 (SD1.2). Moreover, the proportion of DHA was significantly lower in the temporal lobe compared with the frontal, parietal and occipital brain lobes in pigs fed a fish oil diet. In conclusion, the brains of juvenile pigs appear to be responsive to dietary fish oil, although the temporal brain lobe is less responsive compared with the other three brain lobes. The functional consequences of these differences are a challenging focus for future investigation.

  • 7.
    Edebol-Carlman, Hanna
    et al.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre.
    Ljotsson, Brjann
    Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Linton, Steven J.
    Örebro University, School of Law, Psychology and Social Work.
    Boersma, Katja
    Schrooten, Martien
    Örebro University, School of Law, Psychology and Social Work.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre.
    Brummer, Robert J.
    Örebro University Hospital. Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre.
    Face-to-Face Cognitive-Behavioral Therapy for Irritable Bowel Syndrome: The Effects on Gastrointestinal and Psychiatric Symptoms2017In: Gastroenterology Research and Practice, ISSN 1687-6121, E-ISSN 1687-630X, article id 8915872Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a gastrointestinal disorder linked to disturbances in the gut-brain axis. Visceral hypersensitivity and pain are hallmarks of IBS and linked to the physiological and psychological burden and to the nonadaptive coping with stress. Cognitive-behavioral therapy (CBT) for IBS has proven effective in reducing gastrointestinal and psychiatric symptoms in IBS by means of coping with stress. The present pilot study evaluated for the first time whether CBT for IBS affected visceral sensitivity and pain. Individual CBT was performed for 12 weeks in 18 subjects with IBS and evaluated in terms of visceral sensitivity and pain during rectal distensions using the barostat method and self-rated visceral sensitivity and gastrointestinal and psychiatric symptoms. Visceral discomfort, urge, and pain induced by the barostat were not affected by CBT but were stable across the study. However, the level of self-rated visceral sensitivity and gastrointestinal and psychiatric symptoms decreased after the intervention. Central working mechanisms and increased ability to cope with IBS-symptoms are suggested to play a key role in the alleviation of IBS symptoms produced by CBT.

  • 8.
    Edebol-Carlman, Hanna
    et al.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre.
    Schrooten, Martien G. S.
    Örebro University, School of Law, Psychology and Social Work.
    Ljóttson, Brjánn
    Department of Clinical Neuroscience, Division of Psychology and Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Boersma, Katja
    Örebro University, School of Law, Psychology and Social Work.
    Linton, Steven J.
    Örebro University, School of Law, Psychology and Social Work.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre.
    Cognitive behavioral therapy for irritable bowel syndrome: the effects on state and trait anxiety and the autonomic nervous system during induced rectal distensions - An uncontrolled trial2018In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 18, p. 81-91Article in journal (Refereed)
    Abstract [en]

    Background and aims: Irritable bowel syndrome (IBS), is a common multifactorial gastrointestinal disorder linked to disturbances in the microbe gut-brain axis. Cognitive behavioral therapy (CBT), in face-to-face format has showed promising results on IBS and its associated psychological symptoms. The present study explored for the first time if CBT for IBS affects the autonomic nervous system (ANS) during experimentally induced visceral pain and cognitive stress, respectively. The levels of state and trait anxiety, current and perceived stress were also evaluated.

    Methods: In this uncontrolled trial, individual CBT was performed in face-to-face format for 12 weeks in 18 subjects with IBS. Heart rate variability and skin conductance were measured during experimentally induced visceral pain and during a cognitive task (Stroop color-word test), before and after intervention. The levels of state and trait anxiety as well as self-rated current and perceived stress were also measured before and after the intervention.

    Results: CBT did not affect ANS activity during experimentally induced visceral pain and cognitive stress. The sympathetic activity was high, typical for IBS and triggered during both visceral pain and cognitive stress. The levels of state and trait anxiety significantly decreased after the intervention. No significant changes in self-rated current or perceived stress were found.

    Conclusions: Results suggest that face-to-face CBT for IBS improved anxiety- a key psychological mechanism for the IBS pathophysiology, rather than the autonomic stress response to experimentally induced visceral pain and cognitive stress, respectively.

  • 9.
    Engelheart, Stina
    et al.
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Assessment of nutritional status in the elderly: a proposed function-driven model2018In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 62, article id 1366Article in journal (Refereed)
    Abstract [en]

    Background: There is no accepted or standardized definition of 'malnutrition'. Hence, there is also no definition of what constitutes an adequate nutritional status. In elderly people, assessment of nutritional status is complex and is complicated by multi-morbidity and disabilities combined with nutrition-related problems, such as dysphagia, decreased appetite, fatigue, and muscle weakness.

    Objective: We propose a nutritional status model that presents nutritional status from a comprehensive functional perspective. This model visualizes the complexity of the nutritional status in elderly people.

    Design and results: The presented model could be interpreted as the nutritional status is conditional to a person's optimal function or situation. Another way of looking at it might be that a person's nutritional status affects his or her optimal situation. The proposed model includes four domains: (1) physical function and capacity; (2) health and somatic disorders; (3) food and nutrition; and (4) cognitive, affective, and sensory function. Each domain has a major impact on nutritional status, which in turn has a major impact on the outcome of each domain.

    Conclusions: Nutritional status is a multifaceted concept and there exist several knowledge gaps in the diagnosis, prevention, and optimization of treatment of inadequate nutritional status in elderly people. The nutritional status model may be useful in nutritional assessment research, as well as in the clinical setting.

  • 10.
    Ganda Mall, John Peter
    et al.
    Örebro University, School of Medical Sciences.
    Löfvendahl, Lisa
    Örebro University, School of Medical Sciences.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Keita, Å. V.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 13404Article in journal (Refereed)
    Abstract [en]

    Gastrointestinal problems are common in elderly and often associated with psychological distress and increased levels of corticotrophin-releasing hormone, a hormone known to cause mast cell (MC) degranulation and perturbed intestinal barrier function. We investigated if dietary fibres (non-digestible polysaccharides [NPS]) could attenuate MC-induced colonic hyperpermeability in elderly with gastrointestinal (GI) symptoms. Colonic biopsies from elderly with diarrhoea and/or constipation (n = 18) and healthy controls (n = 19) were mounted in Ussing chambers and pre-stimulated with a yeast-derived beta (β)-glucan (0.5 mg/ml) or wheat-derived arabinoxylan (0.1 mg/ml) before the addition of the MC-degranulator Compound (C) 48/80 (10 ng/ml). Permeability markers were compared pre and post exposure to C48/80 in both groups and revealed higher baseline permeability in elderly with GI symptoms. β-glucan significantly attenuated C48/80-induced hyperpermeability in elderly with GI symptoms but not in healthy controls. Arabinoxylan reduced MC-induced paracellular and transcellular hyperpermeability across the colonic mucosa of healthy controls, but did only attenuate transcellular permeability in elderly with GI symptoms. Our novel findings indicate that NPS affect the intestinal barrier differently depending on the presence of GI symptoms and could be important in the treatment of moderate constipation and/or diarrhoea in elderly.

  • 11.
    Ganda Mall, John-Peter
    et al.
    Örebro University, School of Medical Sciences.
    Casado-Bedmar, Maite
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Winberg, Martin E.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Keita, Åsa V.
    A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, no 1, p. 166-178Article in journal (Refereed)
    Abstract [en]

    Background: Administration of β-glucan has shown immune-enhancing effects. Our aim was to investigate whether β-glucan could attenuate mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villus epithelium (VE) of patients with Crohn's disease (CD) and in noninflammatory bowel disease (IBD)-controls. Further, we studied mechanisms of β-glucan uptake and effects on MCs in vitro.

    Methods: Segments of FAE and VE from 8 CD patients and 9 controls were mounted in Ussing chambers. Effects of the MC-degranulator compound 48/80 (C48/80) and yeast-derived β-1,3/1,6 glucan on hyperpermeability were investigated. Translocation of β-glucan and colocalization with immune cells were studied by immunofluorescence. Caco-2-cl1- and FAE-cultures were used to investigate β-glucan-uptake using endocytosis inhibitors and HMC-1.1 to study effects on MCs.

    Results: β-glucan significantly attenuated MC-induced paracellular hyperpermeability in CD and controls. Transcellular hyperpermeability was only significantly attenuated in VE. Baseline paracellular permeability was higher in FAE than VE in both groups, P<0.05, and exhibited a more pronounced effect by C48/80 and β-glucan P<0.05. No difference was observed between CD and controls. In vitro studies showed increased passage, P<0.05, of β-glucan through FAE-culture compared to Caco-2-cl1. Passage was mildly attenuated by the inhibitor methyl-β-cyclodextrin. HMC-1.1 experiments showed a trend to decreasing MC-degranulation and levels of TNF-α but not IL-6 by β-glucan. Immunofluorescence revealed more β-glucan-uptake and higher percentage of macrophages and dendritic cells close to β-glucan in VE of CD compared to controls.

    Conclusions: We demonstrated beneficial effects of β-glucan on intestinal barrier function and increased β-glucan-passage through FAE model. Our results provide important and novel knowledge on possible applications of β-glucan in health disorders and diseases characterized by intestinal barrier dysfunction.

  • 12.
    Ganda Mall, John-Peter
    et al.
    Örebro University, School of Medical Sciences.
    Fart, Frida
    Örebro University, School of Medical Sciences.
    Sabet, Julia
    Örebro University, School of Medical Sciences.
    Lindqvist, Carl-Mårten
    Örebro University, School of Medical Sciences.
    Keita, Åsa V.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Brummer, Robert J.
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Effects of dietary fibres on indomethacin-induced intestinal permeability in elderly: A randomised placebo controlled parallel clinical trialManuscript (preprint) (Other academic)
  • 13.
    Ganda Mall, John-Peter
    et al.
    Örebro University, School of Medical Sciences.
    Löfvendahl, Lisa
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Keita, Åsa V.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptomsManuscript (preprint) (Other academic)
  • 14.
    Ganda Mall, John-Peter
    et al.
    Örebro University, School of Medical Sciences.
    Östlund-Lagerström, Lina
    Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Nutrition and Physical Activity Research Centre, Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Algilani, Samal
    Örebro University, School of Health Sciences.
    Rasoal, Dara
    Örebro University, School of Health Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    V. Keita, Åsa
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?2018In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 18, no 1, article id 75Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Despite the substantial number of older adults suffering from gastrointestinal (GI) symptoms little is known regarding the character of these complaints and whether they are associated with an altered intestinal barrier function and psychological distress. Our aim was to explore the relationship between self-reported gut health, intestinal permeability and psychological distress among older adults.

    METHODS: Three study populations were included: 1) older adults with GI symptoms (n = 24), 2) a group of older adults representing the general elderly population in Sweden (n = 22) and 3) senior orienteering athletes as a potential model of healthy ageing (n = 27). Questionnaire data on gut-health, psychological distress and level of physical activity were collected. Intestinal permeability was measured by quantifying zonulin in plasma. The level of systemic and local inflammation was monitored by measuring C-reactive protein (CRP), hydrogen peroxide in plasma and calprotectin in stool samples. The relationship between biomarkers and questionnaire data in the different study populations was illustrated using a Principal Component Analysis (PCA).

    RESULTS: Older adults with GI symptoms displayed significantly higher levels of both zonulin and psychological distress than both general older adults and senior orienteering athletes. The PCA analysis revealed a separation between senior orienteering athletes and older adults with GI symptoms and showed an association between GI symptoms, psychological distress and zonulin.

    CONCLUSIONS: Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes. This relationship was further confirmed by a PCA plot, which illustrated an association between GI symptoms, psychological distress and intestinal permeability.

  • 15.
    Geraedts, Maartje C. P.
    et al.
    Med Ctr, Dept Human Biol, Maastricht Univ, Maastricht, Netherlands.
    Troost, Freddy J.
    Med Ctr, Dept Internal Med, Div Gastroenterol & Hepatol, Maastricht Univ, Maastricht, Netherlands.
    Tinnemans, Rik
    Med Ctr, Dept Anim Res & Testing Serv, Maastricht Univ, Maastricht, Netherlands.
    Soderholm, Johan D.
    Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences. Med Ctr, Dept Internal Med, Div Gastroenterol & Hepatol, Maastricht Univ, Maastricht, Netherlands.
    Saris, Wim H. M.
    Med Ctr, Dept Human Biol, Maastricht Univ, Maastricht, Netherlands.
    Release of Satiety Hormones in Response to Specific Dietary Proteins Is Different between Human and Murine Small Intestinal Mucosa2010In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 56, no 4, p. 308-313Article in journal (Refereed)
    Abstract [en]

    Background/Aim: High protein diets are the most effective to stimulate cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1) release; however, which proteins are the most potent is not known. Here, the effects of specific dietary proteins on intestinal CCK and GLP-1 release were examined. Methods: Duodenal biopsies of 10 healthy male subjects and 10 male rats were taken and placed in an Ussing chamber system. The biopsies were exposed on the luminal side to buffer, egg protein, codfish protein, ovomucoid, pea protein, and wheat protein. After an exposure time of 2 h, samples were taken from the serosal side. Results: Pea protein and wheat protein increased CCK and GLP-1 release in human duodenal tissue, while codfish protein only increased CCK release. No elevated levels of CCK and GLP-1 were found after exposure of rat tissue to different proteins. Conclusion: Pea and wheat protein are the most potent stimulators of CCK and GLP-1 release in human duodenal tissue, and may therefore be good dietary additives in weight management. Copyright (C) 2010 S. Karger AG, Basel

  • 16.
    Gorreja, Frida
    et al.
    Örebro University, School of Medical Sciences.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Rush, Stephen
    Örebro University, School of Medical Sciences.
    Wall, Rebecca
    Örebro University, School of Medical Sciences.
    De Vos, Willem M.
    Wageningen University & Research Centre, Wageningen, Netherlands; Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Double-blind cross-over trial reveals human mucosal transcriptome responses to variants of LGG administration in vivo2018In: Targeting microbiota: 6th World congress on targeting microbiota towards clinical revolution / [ed] Peter Konturek, Porto, Portugal: ISM , 2018, Vol. 5, article id 978-2-35609-010-2Conference paper (Other academic)
  • 17.
    Gorreja, Frida
    et al.
    Örebro University, School of Medical Sciences.
    Rush, Stephen
    Örebro University, School of Medical Sciences.
    Kasper, Dennis
    Department of Microbiology and Molecular Genetics, Boston, USA; Harvard Medical School, Boston, USA.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Meng, Di
    Harvard Medical School, Boston, USA; Mucosal Immunology Laboratory, Massachusetts General Hospital for Children, Boston, USA.
    Walker, W. Allan
    Harvard Medical School, Boston, USA; Mucosal Immunology Laboratory, Massachusetts General Hospital for Children, Boston, USA.
    Beneficial bacteria that affect Toll-like receptors in the gut immune system: the case of PSA on Bacteroides fragilis and transcription profile of developmentally-regulated genes2018Conference paper (Other academic)
  • 18.
    Gorreja, Frida
    et al.
    Örebro University, School of Medical Sciences.
    Rush, Stephen
    Örebro University, School of Medical Sciences.
    Marques, Tatiana M.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Baker, Adam
    Örebro University, School of Medical Sciences. Head of Discovery, Microbiome and Human Health, Christian Hansen, Danimark.
    Wall, Rebecca
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    The impacts of probiotics and prebiotics on the gut mucosa and immune system through targeting inflammation and intestinal barrier function2018Conference paper (Other academic)
  • 19. Hamer, H. M.
    et al.
    Jonkers, D. M. A. E.
    Loof, A.
    Vanhoutvin, S. A. L. W.
    Troost, F. J.
    Venema, K.
    Kodde, A.
    Koek, G. H.
    Schipper, R. G.
    van Heerde, W. L.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    Analyses of human colonic mucus obtained by an in vivo sampling technique2009In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 41, no 8, p. 559-564Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The mucus layer is an important dynamic component of the epithelial barrier. It contains mucin glycoproteins and other compounds secreted by the intestinal epithelium, such as secretory IgA. However, a standardized in vivo sampling technique of mucus in humans is not yet available.

    AIM: To assess the validity and feasibility of mucin and protein determinations in human colonic mucus collected under physiological conditions.

    SUBJECTS AND METHODS: Triplicate colonic mucus samples were collected in 11 healthy volunteers using cytology brushes during sigmoidoscopy. As an indication of the quantity of collected mucus, total protein and mucin concentrations were determined by measuring oligosaccharide equivalents and monosaccharides. Also secretory IgA and sialic acid concentrations were determined and proteomic analysis was performed using surface enhanced laser desorption/ionization-time of flight-mass spectrometry.

    RESULTS: Mean values of secretory IgA and sialic acid corrected for the amount of mucus ranged from 0.16 to 1.81g secretory IgA/mmol oligosaccharide equivalents and from 12.6 to 48.6g sialic acid/mmol oligosaccharide equivalents. Proteomic analysis of mucus is feasible and cluster analysis showed subject specific profiles. CONCLUSION: Using cytology brushes, human colonic mucus can be sampled and under physiological conditions. These samples could give information on the composition and quality of the mucus layer.

  • 20. Hamer, H. M.
    et al.
    Jonkers, D.
    Venema, K.
    Vanhoutvin, S.
    Troost, F. J.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    Review article: the role of butyrate on colonic function2008In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 27, no 2, p. 104-119Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Butyrate, a short-chain fatty acid, is a main end-product of intestinal microbial fermentation of mainly dietary fibre. Butyrate is an important energy source for intestinal epithelial cells and plays a role in the maintenance of colonic homeostasis. AIM: To provide an overview on the present knowledge of the bioactivity of butyrate, emphasizing effects and possible mechanisms of action in relation to human colonic function. METHODS: A PubMed search was performed to select relevant publications using the search terms: 'butyrate, short-chain fatty acid, fibre, colon, inflammation, carcinogenesis, barrier, oxidative stress, permeability and satiety'. RESULTS: Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis, reinforcing various components of the colonic defence barrier and decreasing oxidative stress. In addition, butyrate may promote satiety. Two important mechanisms include the inhibition of nuclear factor kappa B activation and histone deacetylation. However, the observed effects of butyrate largely depend on concentrations and models used and human data are still limited. CONCLUSION: Although most studies point towards beneficial effects of butyrate, more human in vivo studies are needed to contribute to our current understanding of butyrate-mediated effects on colonic function in health and disease.

  • 21. Hamer, Henrike M.
    et al.
    Jonkers, Daisy M. A. E.
    Bast, Aalt
    Vanhoutvin, Steven A. L. W.
    Fischer, Marc A. J. G.
    Kodde, Andrea
    Troost, Freddy J.
    Venema, Koen
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    Butyrate modulates oxidative stress in the colonic mucosa of healthy humans2009In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 28, no 1, p. 88-93Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Butyrate, a short-chain fatty acid produced by colonic microbial fermentation of undigested carbohydrates, has been implicated in the maintenance of colonic health. This study evaluates whether butyrate plays a role in oxidative stress in the healthy colonic mucosa. METHODS: A randomized, double blind, cross-over study with 16 healthy volunteers was performed. Treatments consisted of daily rectal administration of a 60 ml enema containing 100 mM sodium butyrate or saline for 2 weeks. After each treatment, a blood sample was taken and mucosal biopsies were obtained from the sigmoid colon. In biopsies, the trolox equivalent antioxidant capacity, activity of glutathione-S-transferase, concentration of uric acid, glutathione (GSH), glutathione disulfide and malondialdehyde, and expression of genes involved in GSH and uric acid metabolism was determined. Secondary outcome parameters were CRP, calprotectin and intestinal fatty acid binding protein in plasma and histological inflammatory scores. RESULTS: Butyrate treatment resulted in significantly higher GSH (p<0.05) and lower uric acid (p<0.01) concentrations compared to placebo. Changes in GSH and uric acid were accompanied by increased and decreased expression, respectively, of their rate limiting enzymes determined by RT-PCR. No significant differences were found in other parameters. CONCLUSIONS: This study demonstrated that butyrate is able to beneficially affect oxidative stress in the healthy human colon.

  • 22.
    Hamer, Henrike M.
    et al.
    Dept Internal Med, Div Gastroenterol Hepatol, Nutrim, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Jonkers, Daisy M. A. E.
    Dept Internal Med, Div Gastroenterol Hepatol, Nutrim, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Renes, Ingrid B.
    Dept Pediat, Div Neonatol, Erasmus MC, Rotterdam, Netherlands; Sophia Childrens Univ Hosp, Rotterdam, Netherlands.
    Vanhoutvin, Steven A. L. W.
    Dept Internal Med, Div Gastroenterol Hepatol, Nutrim, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Kodde, Andrea
    Dept Internal Med, Div Gastroenterol Hepatol, Nutrim, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Troost, Freddy J.
    Dept Internal Med, Div Gastroenterol Hepatol, Nutrim, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Venema, Koen
    TI Food & Nutr, Wageningen, Netherlands; Dept Biosci, TNO Qual Life, Zeist, Netherlands.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences. Dept Internal Med, Div Gastroenterol Hepatol, Nutrim, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Butyrate enemas do not affect human colonic MUC2 and TFF3 expression2010In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 22, no 9, p. 1134-1140Article in journal (Refereed)
    Abstract [en]

    Introduction The colonic mucus layer plays an important role in the protection of the intestinal epithelium and mainly consists of mucin glycoproteins (primarily MUC2 in the colon) trefoil factor 3 (TFF3) and secretory IgA. Butyrate is a major end product of fermentation of dietary fibres and is associated with beneficial effects on colonic health. Earlier in-vitro and animal studies showed that butyrate modulates MUC2 and TFF3 expression and mucin secretion, although data from human studies are not yet available. Methods Sixteen healthy volunteers and 35 ulcerative colitis (UC) patients in clinical remission self-administered a 60 ml rectal enema containing 100 mmol/l butyrate or placebo once daily for 2 and 3 weeks, respectively. After each treatment, biopsies were taken from the distal sigmoid for quantitative RT-PCR and immunohistochemical analysis of MUC2 and TFF3. In addition, mucosal sections were stained with high iron diamine-alcian blue to distinguish between sialomucins and sulphomucins. To analyse total mucin secretion and secretory IgA concentrations, 24 h faeces were collected during the day before the endoscopic examination. Results The butyrate intervention did not significantly modulate the expression of MUC2 ( fold change: 1.04 and 1.05 in healthy volunteers and ulcerative colitis patients, respectively) or TFF3 (fold change: 0.91 and 0.94 in healthy volunteers and UC patients, respectively). Furthermore, the percentage of sialomucins, mucus secretion and secretory IgA concentrations were not affected by the butyrate intervention in both the groups. Conclusion Butyrate exposure in healthy volunteers and UC patients in remission did not affect the measured parameters of the colonic mucus layer. Eur J Gastroenterol Hepatol 22: 1134-1140 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

  • 23.
    Hamer, Henrike M.
    et al.
    Dept Internal Med, Div Gastroenterol Hepatol, Med Ctr, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Jonkers, Daisy M. A. E.
    Dept Internal Med, Div Gastroenterol Hepatol, Med Ctr, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Vanhoutvin, Steven A. L. W.
    Dept Internal Med, Div Gastroenterol Hepatol, Med Ctr, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Troost, Freddy J.
    Dept Internal Med, Div Gastroenterol Hepatol, Med Ctr, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Rijkers, Ger
    St Antonius Hosp, Nieuwegein, Netherlands.
    de Bruine, Adriaan
    Dept Pathol, Med Ctr, Maastricht Univ, Maastricht, Netherlands.
    Bast, Aalt
    Dept Pharmacol & Toxicol, Med Ctr, Maastricht Univ, Maastricht, Netherlands.
    Venema, Koen
    TI Food & Nutr, Wageningen, Netherlands; Dept Biosci, TNO Qual Life, Zeist, Netherlands.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences. Dept Internal Med, Div Gastroenterol Hepatol, Med Ctr, Maastricht Univ, Maastricht, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Effect of butyrate enemas on inflammation and antioxidant status in the colonic mucosa of patients with ulcerative colitis in remission2010In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 29, no 6, p. 738-744Article in journal (Refereed)
    Abstract [en]

    Background & Aims: Butyrate, produced by colonic fermentation of dietary fibers is often hypothesized to beneficially affect colonic health. This study aims to assess the effects of butyrate on inflammation and oxidative stress in subjects with chronically mildly elevated parameters of inflammation and oxidative stress.

    Methods: Thirty-five patients with ulcerative colitis in clinical remission daily administered 60 ml rectal enemas containing WO mM sodium butyrate (n = 17) or saline (n = 18) during 20 days (NCT00696098). Before and after the intervention feces, blood and colonic mucosal biopsies were obtained. Parameters of antioxidant defense and oxidative damage, myeloperoxidase, several cytokines, fecal calprotectin and CRP were determined.

    Results: Butyrate enemas induced minor effects on colonic inflammation and oxidative stress. Only a significant increase of the colonic IL-10/IL-12 ratio was found within butyrate-treated patients (p = 0.02), and colonic concentrations of CCL5 were increased after butyrate compared to placebo treatment (p = 0.03). Although in general butyrate did not affect colonic glutathione levels, the effects of butyrate enemas on total colonic glutathione appeared to be dependent on the level of inflammation.

    Conclusion: Although UC patients in remission were characterized by low-grade oxidative stress and inflammation, rectal butyrate enemas showed only minor effects on inflammatory and oxidative stress parameters.

  • 24. He, T.
    et al.
    Venema, K.
    Priebe, M. G.
    Welling, G. W.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    Vonk, R. J.
    The role of colonic metabolism in lactose intolerance2008In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 38, no 8, p. 541-547Article in journal (Refereed)
    Abstract [en]

    Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance.

  • 25.
    Hiyoshi, Ayako
    et al.
    Örebro University, School of Medical Sciences.
    Sabet, Julia A.
    Örebro University, School of Medical Sciences.
    Sjöqvist, Hugo
    Örebro University, Örebro University School of Business.
    Melinder, Carren
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK .
    Precursors in adolescence of adult-onset bipolar disorder2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 218, p. 353-358Article in journal (Refereed)
    Abstract [en]

    Background: Although the estimated contribution of genetic factors is high in bipolar disorder, environmental factors may also play a role. This Swedish register-based cohort study of men examined if physical and psychological characteristics in late adolescence, including factors previously linked with bipolar disorder (body mass index, asthma and allergy), are associated with subsequent bipolar disorder in adulthood. Unipolar depression and anxiety are analysed as additional outcomes to identify bipolar disorder-specific associations.

    Methods: A total of 213,693 men born between 1952 and 1956, who participated in compulsory military conscription assessments in late adolescence were followed up to 2009, excluding men with any psychiatric diagnoses at baseline. Cox regression estimated risk of bipolar disorder, depression and anxiety in adulthood associated with body mass index, asthma, allergy, muscular strength stress resilience and cognitive function in adolescence.

    Results: BMI, asthma and allergy were not associated with bipolar disorder. Higher grip strength, cognitive function and stress resilience were associated with a reduced risk of bipolar disorder and the other disease outcomes.

    Limitations: The sample consisted only of men; even though the characteristics in adolescence pre-dated disease onset, they may have been the consequence of prodromal disease.

    Conclusions: Associations with body mass index and asthma found by previous studies may be consequences of bipolar disorder or its treatment rather than risk factors. Inverse associations with all the outcome diagnoses for stress resilience, muscular strength and cognitive function may reflect general risks for these psychiatric disorders or intermediary factors.

  • 26.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Faecal microbiota transfer in irritable bowel syndrome – clinical outcomes of a randomised placebo- controlled trial2017Conference paper (Refereed)
  • 27.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Fecal Microbiota Transplantation in Irritable Bowel Syndrome – A randomized placebo- controlled trial2017Conference paper (Refereed)
  • 28.
    Karczewski, Jurgen
    et al.
    Host Microbe Interact Grp, Univ Wageningen, Wageningen, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Troost, Freddy J.
    TI Food & Nutr, Wageningen, Netherlands; Div Gastroenterol & Hepatol, Dept Internal Med, Nutr & Toxicol Res Inst Maastricht, Maastricht Univ, Maastricht, Netherlands.
    Konings, Irene
    Host Microbe Interact Grp, Univ Wageningen, Wageningen, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Dekker, Jan
    TI Food & Nutr, Wageningen, Netherlands.
    Kleerebezem, Michiel
    TI Food & Nutr, Wageningen, Netherlands; NIZO Food Res, Ede, Netherlands; Microbiol Lab, Univ Wageningen, Wageningen, Netherlands.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences. TI Food & Nutr, Wageningen, Netherlands; Div Gastroenterol & Hepatol, Dept Internal Med, Nutr & Toxicol Res Inst Maastricht, Maastricht Univ, Maastricht, Netherlands.
    Wells, Jerry M.
    Host Microbe Interact Grp, Univ Wageningen, Wageningen, Netherlands; TI Food & Nutr, Wageningen, Netherlands.
    Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier2010In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 298, no 6, p. G851-G859Article in journal (Refereed)
    Abstract [en]

    Lactobacillus plantarum, a commensal bacterium of humans, has been proposed to enhance the intestinal barrier, which is compromised in a number of intestinal disorders. To study the effect of L. plantarum strain WCFS1 on human barrier function, healthy subjects were administered L. plantarum or placebo in the duodenum for 6 h by means of a feeding catheter. The scaffold protein zonula occludens (ZO)-1 and transmembrane protein occludin were found to be significantly increased in the vicinity of the tight-junction (TJ) structures, which form the paracellular seal between cells of the epithelium. In an in vitro model of the human epithelium, L. plantarum induced translocation of ZO-1 to the TJ region; however, the effects on occludin were minor compared with those seen in vivo. L. plantarum was shown to activate Toll-like receptor 2 (TLR2) signaling, and treatment of Caco-2 monolayers with the TLR2 agonist Pam3-Cys-SK4(PCSK) significantly increased fluorescent staining of occludin in the TJ. Pretreatment of Caco-2 monolayers with L. plantarum or PCSK significantly attenuated the effects of phorbol ester-induced dislocation of ZO-1 and occludin and the associated increase in epithelial permeability. Our results identifying commensal bacterial stimulation of TLR2 in the gut epithelium as a regulator of epithelial integrity have important implications for understanding probiotic mechanisms and the control of intestinal homeostasis.

  • 29.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert-Jan
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital.
    Alteration of the intestinal microbiota as a cause of and a potential therapeutic option in irritable bowel syndrome2014In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 5, no 3, p. 247-261Article, review/survey (Refereed)
    Abstract [en]

    The intestinal microbiota forms a complex ecosystem that is in close contact with its host and has an important impact on health. An increasing number of disorders are associated with disturbances in this ecosystem. Also patients suffering from irritable bowel syndrome (IBS) show an altered composition of their gut microbiota. IBS is a multifactorial chronic disorder characterised by various abdominal complaints and a worldwide prevalence of 10-20%. Even though its aetiology and pathophysiology are complex and not well understood, it is widely accepted that aberrations along the microbe-gut-brain axis are involved. In this review, it will be discussed how exogenous factors, e.g. antibiotics, can cause disbalance in the intestinal microbiota and thereby contribute to the development of IBS. In addition, several new IBS treatment options that aim at re-establishing a healthy, beneficial ecosystem will be described. These include antibiotics, probiotics, prebiotics and faecal transplantation.

  • 30.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Holster, Savanne
    Örebro University, School of Medical Sciences.
    Maaike, Bruins
    DSM Biotechnology Centre, Delft, Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 13100Article in journal (Refereed)
    Abstract [en]

    The Aspergillus niger-derived prolyl endoprotease (AN-PEP) has previously been shown to degrade gluten in healthy subjects when added to an intragastrically infused meal. The current study investigated the efficacy of AN-PEP in a physiological meal setting. In this randomized placebo-controlled crossover study, 18 gluten-sensitive subjects consumed a porridge containing 0.5 g gluten together with two tablets either containing a high or low dose of AN-PEP, or placebo. Gastric and duodenal content was sampled over 180 minutes, and areas under the curve of gluten concentrations were calculated. The primary outcome, i.e. success rate of high dose AN-PEP defined as at least 50% gluten degradation compared to placebo in the duodenum, was achieved in 10 of 13 comparisons. In the stomach, gluten levels were reduced from 176.9 (median, interquartile range 73.5–357.8) to 22.0 (10.6–50.8, p = 0.001) in the high dose and to 25.4 μg × min/ml (16.4–43.7, p = 0.001) in the low dose. In the duodenum, gluten levels were reduced from 14.1 (8.3–124.7) in the placebo to 6.3 (3.5–19.8, p = 0.019) in the high dose and to 7.4 μg × min/ml in the low dose (3.8–12.0, p = 0.015). Thus even in a physiological meal setting, AN-PEP significantly degraded most gluten in the stomach before it entered the duodenum.

  • 31.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Wells, Jerry
    Host–Microbe Interactomics, Animal Sciences, Wageningen University, Wageningen, The Netherlands.
    Cani, Patrice D.
    Metabolism and Nutrition Research Group, WELBIO—Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
    García-Ródenas, Clara L.
    Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
    MacDonald, Tom
    Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
    Mercenier, Annick
    Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
    Whyte, Jacqueline
    European Branch, The International Life Sciences Institute, Brussels, Belgium.
    Troost, Freddy
    Division of Gastroenterology-Hepatology, Department of Internal Medicine, University Hospital Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
    Brummer, Robert-Jan
    Örebro University, School of Medical Sciences.
    Human Intestinal Barrier Function in Health and Disease2016In: Clinical and Translational Gastroenterology, ISSN 2155-384X, E-ISSN 2155-384X, Vol. 7, no 10, article id e196Article, review/survey (Refereed)
    Abstract [en]

    The gastrointestinal tract consists of an enormous surface area that is optimized to efficiently absorb nutrients, water, and electrolytes from food. At the same time, it needs to provide a tight barrier against the ingress of harmful substances, and protect against a reaction to omnipresent harmless compounds. A dysfunctional intestinal barrier is associated with various diseases and disorders. In this review, the role of intestinal permeability in common disorders such as infections with intestinal pathogens, inflammatory bowel disease, irritable bowel syndrome, obesity, celiac disease, non-celiac gluten sensitivity, and food allergies will be discussed. In addition, the effect of the frequently prescribed drugs proton pump inhibitors and non-steroidal anti-inflammatory drugs on intestinal permeability, as well as commonly used methods to assess barrier function will be reviewed.

  • 32.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Is an enzyme supplement for celiac disease finally on the cards?2018In: Expert Review of Gastroenterology & Hepatology, ISSN 1747-4124, E-ISSN 1747-4132, Vol. 12, no 6, p. 531-533Article in journal (Refereed)
  • 33.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert-Jan
    Örebro University, School of Medicine, Örebro University, Sweden.
    Modulation of the gut ecosystem in irritable bowel syndrome2014In: Pharma-Nutrition: an overview / [ed] Gert Folkerts, Johan Garssen, Springer International Publishing , 2014, p. 55-73Chapter in book (Refereed)
  • 34.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ganda-Mall, John-Peter
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rangel, Ignacio
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Edebol-Carlman, Hanna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    The Role of the Gut Microbiota in Brain Function2015In: Probiotics and Prebiotics: Current Research and Future Trends / [ed] Koen Venema & Ana Paula do Carmo, Poole, UK: Caister Academic Press, 2015Chapter in book (Refereed)
  • 35.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Holster, Savanne
    Örebro University, School of Medical Sciences.
    Bruins, Maaike
    DSM Biotechnology Centre, Delft, Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Aspergillus Niger-Derived Enzyme Degrades Gluten in the Stomach of Gluten-Sensitive Subjects2017Conference paper (Refereed)
  • 36.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Holster, Savanne
    Örebro University, School of Medical Sciences.
    Bruins, Maaike
    DSM Biotechnology Centre, Delft, Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Effective gluten degradation in non-coeliac gluten-sensitive subjects by Aspergillus Niger derived enzyme: A placebo-controlled randomized clinical trial2017Conference paper (Refereed)
  • 37.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rangel, Ignacio
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Medicine, Örebro University, Sweden.
    The Role of Lactic Acid Bacteria in the Pathophysiology and Treatment of Irritable Bowel Syndrome (IBS)2013In: Food and Nutrition Sciences, ISSN 2157-944X, E-ISSN 2157-9458, Vol. 4, no 11, p. 27-39Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a multifactorial chronic disorder characterized by various abdominal complaints and a worldwide prevalence of 10% - 20%. Although its etiology and pathophysiology are complex and still not completely understood, aberrations along the microbe-gut-brain axis are known to play a central role. IBS is characterized by inter-related alterations in intestinal barrier function, gut microbe composition, immune activation, afferent sensory signaling and brain activity. Pharmaceutical treatment is generally ineffective and, hence, most therapeutic strategies are based on non-drug approaches. A promising option is the administration of probiotics, in which lactic acid bacteria strains are considered specifically beneficial. This review aims to provide a concise, although comprehensive, overview of the role of lactic acid bacteria in the pathophysiology and treatment of IBS.

  • 38.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Siebenhaar, A.
    Hamburg, Germany.
    Högenauer, C.
    Graz, Austria.
    Arkkila, P.
    Helsinki, Finland.
    Nieuwdorp, M.
    Amsterdam, The Netherlands; Gothenburg, Sweden.
    Norén, Torbjörn
    Örebro University, School of Medical Sciences.
    Ponsioen, C. Y.
    Amsterdam, The Netherlands.
    Rosien, U.
    Hamburg, Germany.
    Rossen, N. G.
    Amsterdam, The Netherlands.
    Satokari, R.
    Helsinki, Finland.
    Stallmach, A.
    Jena, Germany.
    de Vos, W.
    Helsinki, Finland; Wageningen, The Netherlands.
    Keller, J.
    Hamburg, Germany.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Consensus report: Faecal microbiota transfer - clinical applications and procedures2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 45, no 2, p. 222-239Article in journal (Refereed)
    Abstract [en]

    Background: Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication.

    Aim: To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT.

    Methods: Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors.

    Results: Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings.

    Conclusions: Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.

  • 39. Labus, J. S.
    et al.
    Mayer, E. A.
    Jarcho, J.
    Kilpatrick, L. A.
    Kilkens, T. O. C.
    Evers, E. A. T.
    Backes, W. H.
    Brummer, Robert Jan
    Örebro University, School of Health and Medical Sciences.
    van Nieuwenhoven, Michiel A
    Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no 9, p. 1196-1203Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Alterations in serotonin signalling within the brain-gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD.

    METHODS: 12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24-50 years).

    RESULTS: In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C.

    CONCLUSIONS: The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology.

  • 40.
    Marques, Tatiana M.
    et al.
    Örebro University, School of Medical Sciences.
    Holster, Savanne
    Örebro University, School of Medical Sciences.
    Wall, Rebecca
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Correlating the gut microbiome to health and disease2016In: The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota / [ed] Niall Hyland, Catherine Stanton, Elsevier, 2016, p. 261-291Chapter in book (Refereed)
    Abstract [en]

    The gut microbiota is a complex ecosystem consisting of a diverse population of prokaryotes that has a symbiotic relationship with its host; thus it plays a vital role for the host’s health. Our understanding of the effect of the gut microbiome in health and disease has grown substantially over the past 2 decades, mostly because of recent advances in sequencing and other high-throughput technologies. Given its high metabolic potential, close proximity to the intestinal mucosa, and interaction with the immune system, it is not surprising that the gut microbiome is an important partaker in human health. Evidence to the importance of the gut microbiome in human health and disease is the growing number of conditions now linked to changes in the resident gut microbiota, including recurrent Clostridium difficile infections, inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, allergies, neurological diseases, and metabolic diseases. Research into this field of the association of the gut microbiome with health and disease continues to expand at a rapid pace as we come to accept the gut microbiome as our “second genome.” Targeting the gut microbiome to restore/modulate its composition with the use of antibiotics, probiotics, prebiotics, and even fecal microbiota transplantation is considered a promising future strategy for the development of new solutions in the treatment of various diseases associated with an imbalance in microbiota composition and functioning.

  • 41.
    Mekkes, M. C.
    et al.
    Athena Inst, Vrije Univ, Amsterdam, Netherlands.
    Weenen, T. C.
    Erasmus Sch Econ Rotterdam, Erasmus Universiteit Rotterdam, Rotterdam, Netherlands; Erasmus MC, Rotterdam, Netherlands.
    Brummer, Robert J.
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital.
    Claassen, E.
    Athena Inst, Vrije Univ, Amsterdam, the Netherlands; Erasmus MC Rotterdam, Rotterdam, Netherlands.
    The development of probiotic treatment in obesity: a review2014In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 5, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    Recent studies suggested that manipulation of the composition of the microbial ecosystem in the gut might be a novel approach in the treatment of obesity. Such treatment might consist of altering the composition of the microbial communities of an obese individual by administration of beneficial microorganisms, commonly known as probiotics. Here, we intend to contribute to the developmental process of probiotic treatment of human obesity. The aim is to review the evidence regarding the potential effect of probiotic strains on reduction of weight and body fat. A literature study was conducted focusing on clinical trials that examined the effect of specific microorganisms on body weight control. Analysis of the eligible articles pointed out that Lactobacillus gasseri SBT 2055, Lactobacillus rhamnosus ATCC 53103, and the combination of L. rhamnosus ATCC 53102 and Bifidobacterium lactis Bb12 may reduce adiposity, body weight, and weight gain. This suggests that these microbial strains can be applied in the treatment of obesity. Furthermore, short chain fatty acid production and low grade inflammation were found as the underlying mechanisms of action that influence metabolism and affect body weight. These findings might contribute to the development of probiotic treatment of obesity. Further research should be directed to the most effective combination and dosage rate of probiotic microorganisms.

  • 42.
    Melinder, Carren
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hiyoshi, Ayako
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Medicine, Örebro University, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom .
    Decreased stress resilience in young men significantly increases the risk of subsequent peptic ulcer disease: a prospective study of 233 093 men in Sweden2015In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 41, no 10, p. 1005-1015Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Psychosocial stress may influence peptic ulcer disease (PUD) risk, but it can be difficult to identify reliably whether stressful exposures pre-dated disease. The association of stress resilience (susceptibility to stress) with subsequent PUD risk has been incompletely investigated.

    AIM: To assess if stress resilience in adolescence is associated with subsequent PUD risk.

    METHODS: The participants comprised of 233 093 men resident in Sweden, born 1952-1956 and assessed for compulsory military conscription during 1969-1976, with data provided by national Swedish registers. Stress resilience was evaluated through semi-structured interviews by a certified psychologist. Cox regression assessed the association between stress resilience in adolescence and the risk of PUD from 1985 to 2009, between ages 28 and 57 years, with adjustment for parental socioeconomic index, household crowding and number of siblings in childhood, as well as cognitive function and erythrocyte sedimentation rate in adolescence.

    RESULTS: In total, 2259 first PUD diagnoses were identified. Lower stress resilience in adolescence is associated with a higher risk of PUD in subsequent adulthood: compared with high resilience, the adjusted hazard ratios (and 95% CI) are 1.84 (1.61-2.10) and 1.23 (1.09-1.38) for low and moderate stress resilience, respectively.

    CONCLUSION: Stress may be implicated in the aetiology of PUD and low stress resilience is a marker of risk.

  • 43.
    Mohajeri, M. Hasan
    et al.
    DSM Nutritional Products Ltd, Kaiseraugst, Switzerland; University of Zurich, Zurich, Switzerland.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Rastall, Robert A.
    Department of Food and Nutritional Sciences, University of Reading, Reading, UK.
    Weersma, Rinse K.
    Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
    Harmsen, Hermie J. M.
    Department of Medical Microbiology, University Medical Center Groningen, Groningen, The Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.
    Faas, Marijke
    Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.
    Eggersdorfer, Manfred
    DSM Nutritional Products Ltd, Kaiseraugst, Switzerland.
    The role of the microbiome for human health: from basic science to clinical applications2018In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 57, no Suppl. 1, p. S1-S14Article in journal (Refereed)
    Abstract [en]

    The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health and disease, the development of the microbiome in early-life and the role of the microbiome on the gut-brain axis. The gut microbiota changes dramatically during pregnancy and intrinsic factors (such as stress), in addition to extrinsic factors (such as diet, and drugs) influence the composition and activity of the gut microbiome throughout life. Microbial metabolites, e.g. short-chain fatty acids affect gut-brain signaling and the immune response. The gut microbiota has a regulatory role on anxiety, mood, cognition and pain which is exerted via the gut-brain axis. Ingestion of prebiotics or probiotics has been used to treat a range of conditions including constipation, allergic reactions and infections in infancy, and IBS. Fecal microbiota transplantation (FMT) highly effective for treating recurrent Clostridium difficile infections. The gut microbiome affects virtually all aspects of human health, but the degree of scientific evidence, the models and technologies and the understanding of mechanisms of action vary considerably from one benefit area to the other. For a clinical practice to be broadly accepted, the mode of action, the therapeutic window, and potential side effects need to thoroughly be investigated. This calls for further coordinated state-of-the art research to better understand and document the human gut microbiome's effects on human health.

  • 44.
    Montiel Rojas, Diego
    et al.
    Örebro University, School of Health Sciences.
    Nilsson, Andreas
    Örebro University, School of Health Sciences.
    Ponsot, Elodie
    Örebro University, School of Health Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Fairweather-Tait, Susan
    Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
    Jennings, Amy
    Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
    de Groot, Lisette C. P. G. M.
    Department of Human Nutrition, Wageningen University & Research, Wageningen, Netherlands.
    Berendsen, Agnes
    Department of Human Nutrition, Wageningen University & Research, Wageningen, Netherlands.
    Pietruszka, Barbara
    Department of Human Nutrition, Warsaw University of Life Sciences, Warsaw, Poland.
    Madej, Dawid
    Department of Human Nutrition, Warsaw University of Life Sciences, Warsaw, Poland.
    Caumon, Elodie
    Centre de Recherche en Nutrition Humaine d’Auvergne, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.
    Meunier, Nathalie
    Centre de Recherche en Nutrition Humaine d’Auvergne, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.
    Malpuech-Brugere, Corinne
    Unité de Nutrition Humaine, Institut National de la Recherche Agronomique, Centre de Recherche en Nutrition Humaine d’Auvergne, Université Clermont Auvergne, Clermont-Ferrand, France.
    Guidarelli, Giulia
    Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
    Santoro, Aurelia
    Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Interdepartmental Center “L. Galvani” (CIG), University of Bologna, Bologna, Italy.
    Franceschi, Claudio
    Bellaria Hospital, Institute of Neurological Sciences, University of Bologna, Bologna, Italy.
    Kadi, Fawzi
    Örebro University, School of Health Sciences.
    Short Telomere Length Is Related to Limitations in Physical Function in Elderly European Adults2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1110Article in journal (Refereed)
    Abstract [en]

    The present study aims to explore the potential influence of leucocyte telomere length (LTL) on both a single indicator and a composite construct of physical functioning in a large European population of elderly men and women across diverse geographical locations. A total of 1,221 adults (65-79 years) were recruited from five European countries within the framework of NU-AGE study. The physical functioning construct was based on the 36-item Short Form Health Survey. Handgrip strength was used as a single indicator of muscle function and LTL was assessed using quantitative real-time PCR. Women had significantly longer (p < 0.05) LTL than men. Participants in Poland had significantly shorter LTL than in the other study centers, whereas participants in the Netherlands had significantly longer LTL than most of the other centers (p < 0.01). An analysis of LTL as a continuous outcome against physical functioning by using linear models revealed inconsistent findings. In contrast, based on an analysis of contrasting telomere lengths (first vs. fifth quintile of LTL), a significant odds ratio (OR) of 1.7 (95% CI: 1.1 -2.6; p < 0.05) of having functional limitation was observed in those belonging to the first LTL quintile compared to the fifth. Interestingly, having the shortest LTL was still related to a higher likelihood of having physical limitation when compared to all remaining quintiles (OR: 1.5, 95% CI: 1.1 -2.1; p < 0.05), even after adjustment by study center, age, sex, and overweight status. Collectively, our findings suggest that short LTL is an independent risk factor that accounts for functional decline in elderly European populations. The influence of LTL on functional limitation seems driven by the detrimental effect of having short telomeres rather than reflecting a linear dose-response relationship.

  • 45. Nieuwenhuizen, Arie G.
    et al.
    Hochstenbach-Waelen, Ananda
    Veldhorst, Margriet A. B.
    Westerterp, Klaas R.
    Engelen, Mariëlle P. K. J.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    Deutz, Nicolaas E. P.
    Westerterp-Plantenga, Margriet S.
    Acute effects of breakfasts containing alpha-lactalbumin, or gelatin with or without added tryptophan, on hunger, 'satiety' hormones and amino acid profiles2009In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 101, no 12, p. 1859-1866Article in journal (Refereed)
    Abstract [en]

    Proteins are the most satiating macronutrients. Tryptophan (TRP) may contribute to the satiating effect, as it serves as a precursor for the anorexigenic neurotransmitter serotonin. To address the role of TRP in the satiating properties of dietary protein, we compared three different breakfasts, containing either alpha-lactalbumin (high in TRP), gelatin (low in TRP) or gelatin with added TRP (gelatin+TRP, high in TRP), on appetite. Twenty-four subjects (22-29 kg/m2; aged 19-37 years) received a subject-specific breakfast at t = 0 with 10, 55 and 35 % energy from protein, carbohydrate and fat repectively in a randomised, single-blind design. Hunger, glucagon-like peptide (GLP)-1, ghrelin, amino acid concentrations and energy intake during a subsequent lunch were determined. Suppression of hunger was stronger 240 min after the breakfast with alpha-lactalbumin compared with gelatin and gelatin+TRP. Total plasma amino acid concentrations were lower with alpha-lactalbumin compared with gelatin with or without TRP (from t = 180-240 min). TRP concentrations were higher after alpha-lactalbumin than after gelatin with or without TRP from t = 0-100 min, whereas from t = 100-240 min, TRP concentrations were lower after gelatin than after alpha-lactalbumin and gelatin+TRP. The plasma ratio of TRP to other large neutral amino acids (LNAA) was, only at t = 100 min, lower after gelatin+TRP than after the other breakfasts. Plasma amino acid responses, TRP concentrations and TRP:LNAA ratios were not correlated with hunger. GLP-1 and ghrelin concentrations were similar for all diets. Energy intake during a subsequent lunch was similar for all diets. Summarised, an alpha-lactalbumin breakfast suppresses hunger more than a gelatin or gelatin+TRP breakfast. This cannot be explained by (possible) differences found in TRP concentrations and TRP:LNAA ratios in the breakfasts and in plasma, as well as in ciruclating total amino acids, GLP-1 and ghrelin.

  • 46. Nieuwenhuizen, Arie
    et al.
    Westerterp, Klaas
    Veldhorst, Marleen
    Hochstenbach-Waelen, Ananda
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    Mela, David
    Westerterp-Plantenga, Margriet
    Food compositions2009Patent (Other (popular science, discussion, etc.))
  • 47. Nyhlin, Nils
    et al.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Wickbom, Anna
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Abdominal pain is common in microscopic colitis despite remission: a long-term follow-up of 203 patients2008In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, no suppl IArticle in journal (Other academic)
  • 48.
    Rangel, Ignacio
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Sundin, Johanna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fuentes, S.
    Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
    Repsilber, Dirk
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    de Vos, W. M.
    Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands; Departments of Bacteriology & Immunology and Veterinary Biosciences, University of Helsinki, Helsinki, Finland .
    Brummer, Robert Jan
    Örebro University, School of Medicine, Örebro University, Sweden.
    The relationship between faecal-associated and mucosal-associated microbiota in irritable bowel syndrome patients and healthy subjects2015In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 42, no 10, p. 1211-1221Article in journal (Refereed)
    Abstract [en]

    Background: The faecal-associated microbiota is commonly seen as a surrogate of the mucosal-associated microbiota. However, previous studies indicate that they are different. Furthermore, analyses of the mucosal microbiota are commonly done after standard bowel cleansing, affecting the microbial composition.

    Aim: To compare the mucosal-associated microbiota, obtained from unprepared colon, with faecal-associated microbiota in healthy subjects and irritable bowel syndrome (IBS) patients.

    Methods: Faecal and mucosal biopsies were obtained from 33 IBS patients and 16 healthy controls. Of IBS patients, 49% belonged to the diarrhoea-predominant subgroup and 80% suffered from IBS symptoms during at least 5 years. Biopsies were collected from unprepared sigmoid colon and faecal samples a day before colonoscopy. Microbiota analyses were performed with a phylogenetic microarray and redundancy discriminant analysis.

    Results: The composition of the mucosal- and the faecal-associated microbiota in unprepared sigmoid colon differs significantly (P = 0.002). Clinical characteristics of IBS did not correlate with this difference. Bacteroidetes dominate the mucosal-associated microbiota. Firmicutes, Actinobacteria and Proteobacteria dominate the faecal-associated microbiota. Healthy subjects had a significantly higher (P < 0.005) abundance (1.9%) of the bacterial group uncultured Clostridiales I in the mucosal-associated microbiota than IBS patients (0.3%). Bacterial diversity was higher in faecal- compared with mucosal-associated microbiota in IBS patients (P < 0.005). No differences were found in healthy subjects.

    Conclusions: Differences in the mucosal-associated microbiota between healthy individuals and IBS patients are minimal (one bacterial group) compared to differences in the faecal microbiota of both groups (53 bacterial groups). Microbial aberrations characterising IBS are more pronounced in the faeces than in the mucosa.

  • 49.
    Rangel, Ignacio
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Sundin, Johanna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fuentes, Susana
    Wageningen University, Wageningen, The Netherlands.
    Repsilber, Dirk
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    de Vos, Willem M.
    Wageningen University, Wageningen, The Netherlands; University of Helsinki, Finland.
    Brummer, Robert J.
    Örebro University, School of Medicine, Örebro University, Sweden.
    Mucosal-associated microbiota differs less than fecal-associated microbiota between Irritable Bowel Syndrome patients and healthy subjectsManuscript (preprint) (Other academic)
  • 50. Rijkers, Ger T.
    et al.
    de Vos, Willem M.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    Morelli, Lorenzo
    Corthier, Gerard
    Marteau, Philippe
    Health benefits and health claims of probiotics: bridging science and marketing2011In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 106, no 9, p. 1291-1296Article in journal (Refereed)
    Abstract [en]

    Health claims for probiotics are evaluated by the Panel on Dietetic Products, Nutrition and Allergies of the European Food Safety Authority. Despite a substantial amount of basic and clinical research on the beneficial effects of probiotics, all of the evaluated claim applications thus far have received a negative opinion. With the restrictions on the use of clinical endpoints, validated biomarkers for gut health and immune health in relation to reduction in disease risk are needed. Clear-cut criteria for design as well as evaluation of future studies are needed. An open dialogue between basic and clinical scientists, regulatory authorities, food and nutrition industry, and consumers could bridge the gap between science and marketing of probiotics.

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