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Tabat, M. W., Marques, T. M., Markgren, M., Löfvendahl, L., Brummer, R. J. & Wall, R. (2020). Acute Effects of Butyrate on Induced Hyperpermeability and Tight Junction Protein Expression in Human Colonic Tissues. Biomolecules, 10(5), Article ID E766.
Open this publication in new window or tab >>Acute Effects of Butyrate on Induced Hyperpermeability and Tight Junction Protein Expression in Human Colonic Tissues
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2020 (English)In: Biomolecules, E-ISSN 2218-273X, Vol. 10, no 5, article id E766Article in journal (Refereed) Published
Abstract [en]

Intact intestinal barrier function is essential for maintaining intestinal homeostasis. A dysfunctional intestinal barrier can lead to local and systemic inflammation through translocation of luminal antigens and has been associated with a range of health disorders. Butyrate, a short-chain fatty acid derived from microbial fermentation of dietary fibers in the colon, has been described as an intestinal barrier-strengthening agent, although mainly by using in vitro and animal models. This study aimed to investigate butyrate's ability to prevent intestinal hyperpermeability, induced by the mast cell degranulator Compound 48/80 (C48/80), in human colonic tissues. Colonic biopsies were collected from 16 healthy subjects and intestinal permeability was assessed by Ussing chamber experiments. Furthermore, the expression levels of tight junction-related proteins were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Pre-treatment with 5 mM butyrate or 25 mM butyrate did not protect the colonic tissue against induced paracellular or transcellular hyperpermeability, measured by FITC-dextran and horseradish peroxidase passage, respectively. Biopsies treated with 25 mM butyrate prior to stimulation with C48/80 showed a reduced expression of claudin 1. In conclusion, this translational ex vivo study did not demonstrate an acute protective effect of butyrate against a chemical insult to the intestinal barrier in healthy humans.

Keywords
Ussing chamber, butyrate, intestinal barrier function, intestinal permeability, tight junctions
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:oru:diva-81959 (URN)10.3390/biom10050766 (DOI)32422994 (PubMedID)
Available from: 2020-05-20 Created: 2020-05-20 Last updated: 2020-05-20Bibliographically approved
Gorreja, F., Rangel, I., Rush, S., Wall, R., De Vos, W. M. & Brummer, R. J. (2018). Double-blind cross-over trial reveals human mucosal transcriptome responses to variants of LGG administration in vivo. In: Peter Konturek (Ed.), Targeting microbiota: 6th World congress on targeting microbiota towards clinical revolution. Paper presented at 6th World Congress on Targeting Microbiota, Porto, Portugal, October 28-30, 2018. Porto, Portugal: ISM, 5, Article ID 978-2-35609-010-2.
Open this publication in new window or tab >>Double-blind cross-over trial reveals human mucosal transcriptome responses to variants of LGG administration in vivo
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2018 (English)In: 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, Poster (with or without abstract) (Other academic)
Place, publisher, year, edition, pages
Porto, Portugal: ISM, 2018
Series
Archives of international society of microbiota, ISSN 978-2-35609-010-2
National Category
Medical and Health Sciences Genetics
Identifiers
urn:nbn:se:oru:diva-69884 (URN)
Conference
6th World Congress on Targeting Microbiota, Porto, Portugal, October 28-30, 2018
Available from: 2018-10-28 Created: 2018-10-28 Last updated: 2018-11-12Bibliographically approved
Neumann, G., Wall, R., Rangel, I., Marques, T. M. & Repsilber, D. (2018). Qualitative modelling of the interplay of inflammatory status and butyrate in the human gut: a hypotheses about robust bi-stability. BMC Systems Biology, 12(1), Article ID 144.
Open this publication in new window or tab >>Qualitative modelling of the interplay of inflammatory status and butyrate in the human gut: a hypotheses about robust bi-stability
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2018 (English)In: BMC Systems Biology, ISSN 1752-0509, E-ISSN 1752-0509, Vol. 12, no 1, article id 144Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Gut microbiota interacts with the human gut in multiple ways. Microbiota composition is altered in inflamed gut conditions. Likewise, certain microbial fermentation products as well as the lipopolysaccharides of the outer membrane are examples of microbial products with opposing influences on gut epithelium inflammation status. This system of intricate interactions is known to play a core role in human gut inflammatory diseases. Here, we present and analyse a simplified model of bidirectional interaction between the microbiota and the host: in focus is butyrate as an example for a bacterial fermentation product with anti-inflammatory properties.

RESULTS: We build a dynamical model based on an existing model of inflammatory regulation in gut epithelial cells. Our model introduces both butyrate as a bacterial product which counteracts inflammation, as well as bacterial LPS as a pro-inflammatory bacterial product. Moreover, we propose an extension of this model that also includes a feedback interaction towards bacterial composition. The analysis of these dynamical models shows robust bi-stability driven by butyrate concentrations in the gut. The extended model hints towards a further possible enforcement of the observed bi-stability via alteration of gut bacterial composition. A theoretical perspective on the stability of the described switch-like character is discussed.

CONCLUSIONS: Interpreting the results of this qualitative model allows formulating hypotheses about the switch-like character of inflammatory regulation in the gut epithelium, involving bacterial products as constitutive parts of the system. We also speculate about possible explanations for observed bimodal distributions in bacterial compositions in the human gut. The switch-like behaviour of the system proved to be mostly independent of parameter choices. Further implications of the qualitative character of our modeling approach for the robustness of the proposed hypotheses are discussed, as well as the pronounced role of butyrate compared to other inflammatory regulators, especially LPS, NF- κB and cytokines.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Bi-stability, Butyrate, Dynamical model, Dysbiosis, Gut microbiome, Inflammation, Short chain fatty acids
National Category
Gastroenterology and Hepatology Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:oru:diva-70827 (URN)10.1186/s12918-018-0667-6 (DOI)000453547300001 ()30558589 (PubMedID)2-s2.0-85058628095 (Scopus ID)
Funder
Knowledge Foundation, 20110225
Available from: 2018-12-21 Created: 2018-12-21 Last updated: 2019-04-24Bibliographically approved
Gorreja, F., Rush, S., Marques, T. M., Repsilber, D., Baker, A., Wall, R. & Brummer, R. J. (2018). The impacts of probiotics and prebiotics on the gut mucosa and immune system through targeting inflammation and intestinal barrier function. In: : . Paper presented at Food and Inflammation - 2nd Conference of Food Science Sweden, Örebro, Sweden, 21 Nov., 2018.
Open this publication in new window or tab >>The impacts of probiotics and prebiotics on the gut mucosa and immune system through targeting inflammation and intestinal barrier function
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2018 (English)Conference paper, Oral presentation only (Other academic)
Keywords
Probiotics, Inflammation, Prebiotics, Immune system, Dietary
National Category
Medical and Health Sciences Microbiology
Research subject
Molecular Biology; Medicine; Microbiology
Identifiers
urn:nbn:se:oru:diva-70257 (URN)
Conference
Food and Inflammation - 2nd Conference of Food Science Sweden, Örebro, Sweden, 21 Nov., 2018
Available from: 2018-11-21 Created: 2018-11-21 Last updated: 2019-04-24Bibliographically approved
Wall, R., Marques, T., Edebol-Carlman, H., Sundin, J., Vumma, R., Rangel, I. & Brummer, R. J. (2017). Altered expression of membrane transporters in colonic mucosa of patients with Irritable Bowel Syndrome (IBS) and Post-infectious (PI)-IBS compared to healthy subjects. Neurogastroenterology and Motility, 29(Suppl. 2), 107-108
Open this publication in new window or tab >>Altered expression of membrane transporters in colonic mucosa of patients with Irritable Bowel Syndrome (IBS) and Post-infectious (PI)-IBS compared to healthy subjects
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2017 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 29, no Suppl. 2, p. 107-108Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Irritable bowel syndrome (IBS) affects 5%- 15% of adults in the general population, and is characterized by chronic recurrent abdominal pain and discomfort and associated with altered bowel habits. The pathophysiology of IBS is complex and not fully under-stood. Hence, treatment is often based on symptomatology rather than underlying physiological aberrancies.

Objective: To compare the expression of membrane transporters in mucosal biopsies of healthy subjects, IBS patients and post- infectious (PI)- IBS patients.

Methods: Mucosal biopsies were obtained from the unprepared sigmoid colon in 18 IBS patients, 9 PI- IBS patients and 10 healthy subjects. Total RNA was isolated and prepared for gene expression analyses using quantitative reverse- transcription polymerase chain reaction (qRT- PCR). We compared the expression of genes encoding membrane- spanning transporters, using GAPDH as a reference gene, and by using the comparative 2- ΔΔCt method.

Results: Colonic expression of SCL7A5 and SLC3A2 (together com-prising the amino acid transporter LAT1+4F2hc) was significantly lower in IBS patients, but not in PI- IBS patients, compared to healthy controls (P<.001). The expression of SLC7A8 (LAT2) tended to be lower in IBS patients compared to controls (P=.06). Mucosal gene ex-pression of the short chain fatty acid transporter SMCT1 (SLC5A8) was lower in both IBS- patients and PI- IBS patients compared to healthy subjects (P<.01).

Conclusions: The amino acid transporters LAT1 and LAT2 appeared to be affected in IBS patients, but not in PI- IBS patients, compared to healthy subjects, suggesting a possible alteration in amino acids transport in this patient group. Furthermore, our results suggest a lower uptake of short chain fatty acids in both IBS- and PI- IBS pa-tients. Altered expression of these transporters may be involved in the pathophysiology of IBS as well as being a potential biomarker of this aberration, and therefore deserves further study in IBS.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
National Category
Gastroenterology and Hepatology Neurology
Identifiers
urn:nbn:se:oru:diva-60601 (URN)10.1111/nmo.13180 (DOI)000407643600220 ()
Available from: 2017-09-05 Created: 2017-09-05 Last updated: 2019-04-24Bibliographically approved
Marques, T. M., Holster, S., Wall, R., König, J. & Brummer, R. J. (2016). Correlating the gut microbiome to health and disease. In: Niall Hyland, Catherine Stanton (Ed.), The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota (pp. 261-291). Elsevier
Open this publication in new window or tab >>Correlating the gut microbiome to health and disease
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2016 (English)In: 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.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Gut microbiota, Immune system-related diseases, Intestinal diseases, Metabolic diseases, Nervous system-related diseases, Therapies for gut microbiota modulation
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-65939 (URN)10.1016/B978-0-12-802304-4.00012-8 (DOI)2-s2.0-85011779736 (Scopus ID)978-0-12-802304-4 (ISBN)
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2019-04-24Bibliographically approved
Marques, T. M., Patterson, E., Wall, R., O'Sullivan, O., Fitzgerald, G. F., Cotter, P. D., . . . Stanton, C. (2016). Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model. Beneficial Microbes, 7(3), 409-420
Open this publication in new window or tab >>Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model
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2016 (English)In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 7, no 3, p. 409-420Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~10(9)microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~10(9) L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P<0.05), but did not alter other metabolic markers in healthy rats. Diabetes induced by STZ injection decreased body weight (P<0.05), increased intestinal length (P<0.05) and stimulated water and food intake. Insulin was decreased (P<0.05), whereas glucose was increased (P<0.001) in all diabetic groups, compared with non-diabetic controls. A decrease (P<0.01) in glucose levels was observed in diabetic rats receiving L. brevis DPC 6108, compared with diabetic-controls. Both the composition and diversity of the intestinal microbiota were affected by diabetes. Microbial diversity in diabetic rats supplemented with low GABA was not reduced (P>0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.

Place, publisher, year, edition, pages
Wageningen, Netherlands: Wageningen Academic Publishers, 2016
Keywords
Streptozotocin, type-1 diabetes, probiotic, γ-aminobutyric acid
National Category
Medical and Health Sciences Endocrinology and Diabetes
Identifiers
urn:nbn:se:oru:diva-54343 (URN)10.3920/BM2015.0154 (DOI)000376602400011 ()27013462 (PubMedID)2-s2.0-84971645676 (Scopus ID)
Note

Funding Agencies:

APC Microbiome Institute 

Science Foundation Ireland (SFI) 

Available from: 2017-01-09 Created: 2017-01-09 Last updated: 2019-04-24Bibliographically approved
Marques, T. M., Wall, R., O'Sullivan, O., Fitzgerald, G. F., Shanahan, F., Quigley, E. M., . . . Stanton, C. (2015). Dietary trans-10, cis-12-conjugated linoleic acid alters fatty acid metabolism and microbiota composition in mice. British Journal of Nutrition, 113(5), 728-738
Open this publication in new window or tab >>Dietary trans-10, cis-12-conjugated linoleic acid alters fatty acid metabolism and microbiota composition in mice
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2015 (English)In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 113, no 5, p. 728-738Article in journal (Refereed) Published
Abstract [en]

The main aim of the present study was to investigate the effects of dietary trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) on intestinal microbiota composition and SCFA production. C57BL/6 mice (n 8 per group) were fed a standard diet either supplemented with t10c12-CLA (0·5 %, w/w) (intervention) or with no supplementation (control), daily for 8 weeks. Metabolic markers (serum glucose, leptin, insulin and TAG, and liver TAG) were assessed by ELISA commercial kits, tissue long-chain fatty acids and caecal SCFA by GC, and microbial composition by 16S rRNA pyrosequencing. Dietary t10c12-CLA significantly decreased visceral fat mass (P< 0·001), but did not affect body weight (intervention), when compared with no supplementation (control). Additionally, lipid mass and composition were affected by t10c12-CLA intake. Caecal acetate, propionate and isobutyrate concentrations were higher (P< 0·05) in the t10c12-CLA-supplemented group than in the control group. The analysis of the microbiota composition following 8 weeks of t10c12-CLA supplementation revealed lower proportions of Firmicutes (P= 0·003) and higher proportions of Bacteroidetes (P= 0·027) compared with no supplementation. Furthermore, t10c12-CLA supplementation for 8 weeks significantly altered the gut microbiota composition, harbouring higher proportions of Bacteroidetes, including Porphyromonadaceae bacteria previously linked with negative effects on lipid metabolism and induction of hepatic steatosis. These results indicate that the mechanism of dietary t10c12-CLA on lipid metabolism in mice may be, at least, partially mediated by alterations in gut microbiota composition and functionality.

Place, publisher, year, edition, pages
Cambridge, United Kingdom: Cambridge University Press, 2015
Keywords
Trans-10, cis-12-Conjugated linoleic acid, Intestinal microbiota, Lipid metabolism
National Category
Medical and Health Sciences Nutrition and Dietetics
Identifiers
urn:nbn:se:oru:diva-46356 (URN)10.1017/S0007114514004206 (DOI)000352199200003 ()25697178 (PubMedID)2-s2.0-84926421360 (Scopus ID)
Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2018-08-31Bibliographically approved
Wall, R., Cryan, J. F., Ross, R. P., Fitzgerald, G. F., Dinan, T. G. & Stanton, C. (2014). Bacterial neuroactive compounds produced by psychobiotics. Advances in Experimental Medicine and Biology, 817, 221-239
Open this publication in new window or tab >>Bacterial neuroactive compounds produced by psychobiotics
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2014 (English)In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 817, p. 221-239Article in journal (Refereed) Published
Abstract [en]

We recently coined the phrase 'psychobiotics' to describe an emerging class of probiotics of relevance to psychiatry [Dinan et al., Biol Psychiatry 2013;74(10):720-726]. Such "mind-altering" probiotics may act via their ability to produce various biologically active compounds, such as peptides and mediators normally associated with mammalian neurotransmission. Several molecules with neuroactive functions such as gamma-aminobutyric acid (GABA), serotonin, catecholamines and acetylcholine have been reported to be microbially-derived, many of which have been isolated from bacteria within the human gut. Secreted neurotransmitters from bacteria in the intestinal lumen may induce epithelial cells to release molecules that in turn modulate neural signalling within the enteric nervous system and consequently signal brain function and behaviour of the host. Consequently, neurochemical containing/producing probiotic bacteria may be viewed as delivery vehicles for neuroactive compounds and as such, probiotic bacteria may possibly have the potential as a therapeutic strategy in the prevention and/or treatment of certain neurological and neurophysiological conditions.

Place, publisher, year, edition, pages
New York, USA: Springer, 2014
National Category
Medical and Health Sciences Microbiology
Identifiers
urn:nbn:se:oru:diva-46358 (URN)10.1007/978-1-4939-0897-4_10 (DOI)000345993500012 ()24997036 (PubMedID)2-s2.0-84909646516 (Scopus ID)
Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2017-12-01Bibliographically approved
London, L. E. E., Kumar, A. H. S., Wall, R., Casey, P. G., O'Sullivan, O., Shanahan, F., . . . Stanton, C. (2014). Exopolysaccharide-producing probiotic Lactobacilli reduce serum cholesterol and modify enteric microbiota in ApoE-deficient mice. Journal of Nutrition, 144(12)
Open this publication in new window or tab >>Exopolysaccharide-producing probiotic Lactobacilli reduce serum cholesterol and modify enteric microbiota in ApoE-deficient mice
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2014 (English)In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 144, no 12Article in journal (Refereed) Published
Abstract [en]

Background: Probiotic bacteria have been associated with a reduction in cardiovascular disease risk, a leading cause of death and disability.

Objectives: The aim of this study was to assess the impact of dietary administration of exopolysaccharide-producing probiotic Lactobacillus cultures on lipid metabolism and gut microbiota in apolipoprotein E (apoE)-deficient mice.

Methods: First, we examined lipid metabolism in response to dietary supplementation with recombinant β-glucan-producing Lactobacillus paracasei National Food Biotechnology Centre (NFBC) 338 expressing the glycosyltransferase (Gtf) gene from Pediococcus parvulus 2.6 (GTF), and naturally exopolysaccharide-producing Lactobacillus mucosae Dairy Product Culture Collection (DPC) 6426 (DPC 6426) compared with the non-β-glucan-producing isogenic control strain Lactobacillus paracasei NFBC 338 (PNZ) and placebo (15% wt:vol trehalose). Second, we examined the effects on the gut microbiota of dietary administration of DPC 6426 compared with placebo. Probiotic Lactobacillus strains at 1 × 10(9) colony-forming units/d per animal were administered to apoE(-/-) mice fed a high-fat (60% fat)/high-cholesterol (2% wt:wt) diet for 12 wk. At the end of the study, aortic plaque development and serum, liver, and fecal variables involved in lipid metabolism were analyzed, and culture-independent microbial analyses of cecal content were performed.

Results: Total cholesterol was reduced in serum (P < 0.001; ∼33-50%) and liver (P < 0.05; ∼30%) and serum triglyceride concentrations were reduced (P < 0.05; ∼15-25%) in mice supplemented with GTF or DPC 6426 compared with the PNZ or placebo group, respectively. In addition, dietary intervention with GTF led to increased amounts of fecal cholesterol excretion (P < 0.05) compared with all other groups. Compositional sequencing of the gut microbiota revealed a greater prevalence of Porphyromonadaceae (P = 0.001) and Prevotellaceae (P = 0.001) in the DPC 6426 group and lower proportions of Clostridiaceae (P < 0.05), Peptococcaceae (P < 0.001), and Staphylococcaceae (P < 0.01) compared with the placebo group.

Conclusion: Ingestion of exopolysaccharide-producing lactobacilli resulted in seemingly favorable improvements in lipid metabolism, which were associated with changes in the gut microbiota of mice.

Place, publisher, year, edition, pages
Bethesda: American Society for Nutrition, 2014
Keywords
probiotics, lactobacilli, exopolysaccharide, cholesterol, gut microbiota, lipid metabolism
National Category
Medical and Health Sciences Nutrition and Dietetics
Identifiers
urn:nbn:se:oru:diva-46357 (URN)10.3945/jn.114.191627 (DOI)000345199500011 ()25320181 (PubMedID)2-s2.0-84912036309 (Scopus ID)
Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2018-09-16Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-3355-9452

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