To Örebro University

Dietary fibers (DF) from plant-based foods promote health benefits through their physicochemical properties and fermentation by the gut microbiota, often studied in relation to changes in gut microbiota profile and production of gut microbiota-derived metabolites. Here, we characterized structural motifs (i.e., oligomers) produced during DF breakdown upon colonic fermentation and explored their interaction with toll-like receptors (TLRs) present on the surface of human intestinal and immune system cells. Wheat arabinoxylan (WAX) was subjected to in vitro colonic fermentation, with its structural motifs identified and tracked throughout the fermentation process. Using carbohydrate-active enzymes, six well-defined fractions of arabinoxylans and linear xylans identified during colonic fermentation were produced and tested for interaction with tool-like receptors (TLR)2 and TLR4 via reporter cell assay. The results showed structure-dependent effects, with TLR2 inhibition and TLR4 activation varying based on the degree of polymerization and branching. Molecular docking confirmed that minor structural changes in oligomers structure significantly influenced these interactions. The study supports the hypothesis that oligomers and polysaccharides affect cell receptors through complex, multi-receptor interactions, and highlights the potential for enzymatic tailoring of DF to create functional ingredients with targeted effects on human health.

This perspective article is a product of the work of an expert group within the Prebiotic Task Force convened by the International Life Sciences Institute Europe (ILSI Europe), a non-profit organization that brings together experts from academia, industry and public service to catalyse nutrition science for public benefit. An expert group was conceived in October 2023 to discuss the evidence base on the use of prebiotics to promote cognitive functioning, with a focus on highlighting knowledge gaps and proposing a list of recommendations to guide this specific area of research forward. To address this, we evaluated existing systematic reviews and meta-analyses of human intervention studies that examine the effects of prebiotics on cognitive functioning. These are predominantly conducted in healthy participants under basal conditions and have, to date, revealed limited effects. In this perspective, we propose that prebiotics should be investigated as agents to promote cognitive resilience by testing their effects on cognitive performance under certain cognition-taxing factors that individuals encounter across their lifespan. These include stress, poor sleep outcomes, sedentary behaviour, and unhealthy dietary patterns, all of which have been shown to be associated with altered microbiome and impact global cognition or specific cognitive domains. In addition, we recommend identifying vulnerable populations that are either sub-clinical or that struggle chronically or periodically with one or more cognition-taxing factors, to better uncover the boundary conditions for prebiotic effectiveness. By broadening the scope of research to include diverse populations and challenging conditions in daily life or experimental settings, we can expand our understanding of the role of prebiotics not only in cognitive health or impairment, but also as potential preventative agents that may promote cognitive resilience during aging and in response to various lifestyle-related challenges.

Aim: The cell matrix of plant foods has received little attention in prebiotic fiber research. We aimed to understand the impact of the plant cell matrix in dried chicory root on its breakdown in the human gut to explain its reported beneficial effects on gut and metabolic health.

Methods: We applied in vitro digestion and fermentation models together with an ex vivo gut barrier integrity model. Plant cell matrix intactness in the upper gastrointestinal tract was investigated by scanning electron microscopy. Colonic breakdown of inulin, and chicory root cubes and powder was assessed by gut microbiota analysis using 16S rRNA gene amplicon sequencing and determining the kinetics of changes in pH, gas, and short- chain fatty acid (SCFA) production. Finally, effects on gut barrier integrity were explored by exposing colonic biopsies to fermentation supernatants in an Ussing chamber model.

Results: The plant cell matrix of dried chicory root cubes remained intact throughout upper gastrointestinal transit. Dried chicory root fermentation resulted in higher final relative abundances of pectin-degrading Monoglobus and butyrate-producing Roseburia spp. compared to inulin and a seven-fold increase in Bifidobacterium spp. in donors where these species were present. Dried chicory root cubes yielded similar total SCFAs but higher final butyrate levels than chicory root powder or isolated inulin with less gas produced. No uniform but donor-specific effects of fermentation supernatants on the maintenance of gut barrier integrity were detected.

Conclusion: The intact plant cell matrix of dried chicory root affected its colonic breakdown kinetics and microbiota, underpinning its beneficial effect in vivo.

Strenuous exercise can result in disruption of intestinal barrier function and occurrence of gastrointestinal symptoms. The aim of this exploratory study was to elucidate systemic effects of increased intestinal permeability after high-intensity exercise. Forty-one endurance-trained subjects performed a 60-min treadmill run at 80% VO2max. Small intestinal permeability was measured as urinary excretion ratio of lactulose/rhamnose (L/R). Blood, saliva and feces were analyzed for gut barrier and immune-related biomarkers. The exercise challenge increased several markers of intestinal barrier disruption, immune function and oxidative stress. We found a negative correlation between L/R ratio and uric acid (r = -0.480), as well as a positive correlation between the L/R ratio and fecal chromogranin A in male participants (r = 0.555). No significant correlations were found between any of the markers and gastrointestinal symptoms, however, perceived exertion correlated with the combination of IL-6, IL-10 and salivary cortisol (r = 0.492). The lack of correlation between intestinal permeability and gastrointestinal symptoms could be due to minor symptoms experienced in lab settings compared to real-life competitions. The correlation between L/R ratio and uric acid might imply a barrier-protective effect of uric acid, and inflammatory processes due to strenuous exercise seem to play an important role regarding physical exhaustion.

Since lack of culture-specific foods in dietary assessment methods may bias reported dietary intake, we identified foods and dishes consumed by residents not born in Sweden and describe consequences for reported foods and nutrient intake using a culturally adapted dietary assessment method. Design consisted of cross-sectional data collection using (semi-)qualitative methods of dietary assessment (and national diet survey instrument RiksmatenFlex) with subsequent longitudinal data collection using quantitative methods for method comparison (December 2020-January 2023). Three community-based research groups were recruited that consisted of mothers born in Sweden, Syria/Iraq, and Somalia, with a median age of 34, 37, and 36 years, respectively. Women born in Syria/Iraq and Somalia who had lived in Sweden for approximately 10 years, reported 78 foods to be added to RiksmatenFlex. In a subsequent study phase, 69% of these foods were reported by around 90% of the ethnic minority groups and contributed to 17% of their reported energy intake. However, differences between the three study groups in median self-reported energy intake remained (Sweden 7.19 MJ, Syria/Iraq 5.54 MJ, and Somalia 5.69 MJ). The groups also showed differences in relative energy contribution from fats and carbohydrates, as well as differences in energy intake from food groups such as bread and sweet snacks. We conclude that a dietary assessment instrument containing culture-specific foods could not resolve group differences in reported energy intake, although these foods provided content validity and contributed 17% of energy intake. The dietary habits collected in this study serve to develop new dietary assessment instruments.

The appropriateness of the fecal microbiota to adequately reflect the gut microbiota composition from more difficult to access luminal content at different colonic locations has been debated. Here, in a healthy population, luminal samples were collected from terminal ileum to rectum using an unique sampling technique without the need of prior bowel cleansing/preparation. Rectal swabs were collected immediately prior colonoscopy by an experienced physician, and fecal samples were collected at home by the participants themselves. Microbiota composition was evaluated as relative abundance, α-diversity and Bray-Curtis dissimilarities. Our data suggest that fecal samples and rectal swabs present noninvasive, easily accessible, low-cost sampling tools that are accurate proxies to characterize luminal large intestinal microbiota composition.

Serious infections may result in greater risk of Parkinson's disease. However, high-quality cohort studies focusing on a potential causal role of different types and sites of infection are lacking. Gastrointestinal infections are of a particular interest due to growing evidence implicating gut dysbiosis in Parkinson's disease aetiology. This population-based cohort study used the Swedish Total Population Register to identify individuals born during 1944-77 and resident in Sweden between 1990 and 2018 (N = 3 698 319). Hospital-treated infections at ages 21-30 and 31-40 years were identified from the National Patient Register. Participants were followed to identify Parkinson's disease diagnoses from age 41 years up to December 31, 2018, when the oldest individual reached 75 years. Cox regression with a sibling comparison design to tackle familial genetic and environmental confounding was used to derive hazard ratios and 95% confidence intervals for each infection site, type, or any infections at ages 21-30 and 31-40 years. During a median follow-up of 15.4 years, 8815 unique Parkinson's disease diagnoses were accrued, with a crude rate of 17.3 (95% confidence interval 17.0, 17.7) per 100 000 person-years. After controlling for shared familial factors, hospital-treated gastrointestinal and respiratory infections between 21 and 30 years of age were associated with a greater risk of Parkinson's disease [hazard ratios 1.35 (95% confidence interval: 1.05, 1.75) and 1.45 (95% confidence interval: 1.08, 1.95), respectively]; no association was found for any infections at age 31-40 [hazard ratio 1.05 (95% confidence interval: 0.93, 1.19)]. After adjustment, no statistically significant associations were observed for other sites including genitourinary and skin. These findings suggest that hospital-treated infections of the gastrointestinal tract and lungs, both of which may have an influence on the gut microbiome, by age 30 years may be risk factors for Parkinson's disease.

Fecal Microbiota Transplantation (FMT) has shown to possess impressive potential benefit for a wide range of clinical indications. Due to its inherent safety issues and efficacy constraints, the use of personalized FMT analogs could be a promising avenue. The development of such analogs will require a detailed understanding of their functionality, encompassing not only microbe-host interactions of the microbial taxa that are involved, but also of the ecological dimensions of the analogs and an overview of the gastrointestinal sites where these relevant microbial interactions take place. Moreover, characterization of taxa that have been lost due to diminished exposure to beneficial microbes, as a consequence of Western lifestyle, may lead to creation of future FMT analogs with the capacity to restore functionalities that we have lost.

BACKGROUND: An increased intestinal permeability is a common feature in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Probiotics have shown to improve IBS symptoms and might also affect intestinal barrier function.

AIM: The aim of this study was to investigate the effects of a 6-week intervention with Limosilactobacillus reuteri ATCC PTA 6475 alone (single strain) or in combination with Limosilactobacillus reuteri DSM 17938 (dual strain) on gut barrier function, immune markers, and symptoms in IBS-D patients (ClinicalTrials.gov registration number: NCT03986476).

METHODS: 65 IBS-D patients were randomised into three groups (placebo, single strain, dual strain). Small and large intestinal permeability were assessed using a multi-sugar urinary recovery test. Blood, saliva, faecal samples, and several symptom scales were collected before, and after three and six weeks of intervention.

RESULTS: Small and large intestinal permeability as well as other markers of gut barrier function were not significantly affected by the probiotic interventions. Serum IL-6 levels showed a tendency to be reduced in the single strain group (descriptive p = 0.052). In addition, high-sensitivity C-reactive protein was significantly reduced in the dual strain group (p = 0.041). The participants in both treatment groups reported less gastrointestinal symptoms after three weeks, but this reached significance only in the dual strain group (total score: p = 0.032, pain subscore: p = 0.028). After six weeks, none of the assessed symptoms were significantly different from the placebo.

CONCLUSION: The probiotic compounds investigated in this study did not seem to affect IBS-D patients' gut barrier function, but showed potential anti-inflammatory and symptom-improving properties, which need to be confirmed in larger study cohorts.