Effects of low and high FODMAP diets on human gastrointestinal microbiota composition in adults with intestinal diseases : a systematic review

A diet high in non-digestible carbohydrates is known to promote health, in part through its effect on the gut microbiome. While substantially proven for healthy individuals, these effects are more ambiguous in subjects with intestinal diseases. At the same time, a diet low in these fermentable carbohydrates, the low FODMAP (acronym for Fermentable Oligo-, Di-, Mono-saccharides, And Polyols) diet, is gaining popularity as a treatment option for symptom relief in irritable bowel syndrome and inflammatory bowel disease. There are, however, several indications that this diet induces effects opposite to those of prebiotic supplementation, resulting in gut microbiome changes that might be detrimental. Here, we provide a systematic review of the effects of low and high FODMAP diets on human gastrointestinal microbiota composition in adults with intestinal diseases, through literature screening using the databases PubMed, Embase, and Web of Science. We summarize study findings on dietary impact in patients, including the effect on bacterial taxa and diversity. In general, similar to healthy subjects, restricting non-digestible carbohydrate intake in patients with intestinal diseases has opposite effects compared to prebiotic supplementation, causing a reduction in bifidobacteria and an increase in bacteria associated with dysbiosis. Future studies should focus on assessing whether the induced microbial changes persist over time and have adverse effects on long-term colonic health

Sex Determination:Why So Many Ways of Doing It?

Sexual reproduction is an ancient feature of life on earth, and the familiar X and Y chromosomes in humans and other model species have led to the impression that sex determination mechanisms are old and conserved. In fact, males and females are determined by diverse mechanisms that evolve rapidly in many taxa. Yet this diversity in primary sex-determining signals is coupled with conserved molecular pathways that trigger male or female development. Conflicting selection on different parts of the genome and on the two sexes may drive many of these transitions, but few systems with rapid turnover of sex determination mechanisms have been rigorously studied. Here we survey our current understanding of how and why sex determination evolves in animals and plants and identify important gaps in our knowledge that present exciting research opportunities to characterize the evolutionary forces and molecular pathways underlying the evolution of sex determination

Identificatie van covarianten van het menselijk darm microbioom.

Summary More than eighty years after the isolation of the first gastrointestinal bacterium in 1885, research on the microbes inside our body finally took off. Since then, improvements in culturing techniques paved the way for the exploration of the complex microbial community inside our guts. In the last decades, the rapid development of sequencing approaches, allowing the identification of our microbial companions based on their DNA, has speeded up the field of gut microbiome research substantially. Sequencing-based assessment of microbial communities in human fecal material in medium-scale (N<400), cross-sectional studies have now linked alterations in gut microbiota composition to disease, as well as chronically suboptimal health and wellbeing. The discovery of these associations has stimulated the search for specific microbiome-based biomarkers for a wide range of pathologies. However, major challenges still hamper the once assumed imminent translation of microbiome monitoring into diagnostic and clinical practice. One such hurdle is the lack of knowledge on the impact of host and environmental factors on microbiota variation within a healthy population, which is essential for robust disease marker identification. In this thesis we applied a two fold strategy to improve knowledge about the functioning and population-level variability of the gut microbial-human ecosystem in healthy individuals. First, we aimed to facilitate the scale up of faecal sampling initiatives by upgrading time and cost-efficiency of the ‘golden standard’ of fecal sampling procedures, while maintaining or improving user-experience, such that the large numbers necessary to detect a presumed signal in a background of multiple confounders can be obtained faster and with fewer resources. Second, we characterized the effect of specific parameters on the gut-ecosystem, thereby contributing to a better understanding of the factors driving it, and consequently aiding future gut microbiome studies through improved study design, confounder analyses and interpretation of results. For the first objective, facilitating the scale up of faecal sampling initiatives, we evaluated current collection and preservation techniques of fecal samples for microbiome research on various aspects, including among others userfriendliness, cost, and effect on observed microbiota compostion. Although immediate freezing of samples can still be considered the golden standard, the substantial processing costs associated to such protocols, which mostly stem from cold chain management and aliquotting frozen material under sterile conditions in the laboratory, is the main reason to opt for buffer-based solutions (chapter 3). We designed two new, improved fecal sampling devices allowing rapid aliquotting of frozen fecal material. These devices reduce processing time and cost related to frozen fecal sampling and combine this with similar or improved user-experience for study participants. With the proposed devices large-scale, high-quality sampling would be no longer cost-prohibitive (chapter 4). Several studies were carried out in order to characterize the effect of specific parameters on the gut-ecosystem, as stated in the second objective. Building upon the rich metadata of the Flemish Gut Flora project, a large-scale (N>1000) research effort based in Belgium and an equally scaled Dutch validation cohort, we identified a set of 69 microbiota covariates with a replication rate of over 92% and a cumulative, nonredundant effect size of 7.63%. The observed small effect size suggests the influence of additional, currently unknown covariates as well as intrinsic microbial ecological processes such as founder effects, species interactions, and dynamics. Out of a total of 503 parameters, stool consistency, as measured by self-assessed Bristol stool scale (BSS) score, emerged as the top feature covarying with fecal microbiome composition. We demonstrated in several study cohorts that stool consistency strongly correlates with all known major microbiome markers. It is negatively correlated with species richness (the number of species in a sample) and linked to the relative abundance of key species Akkermansia and Methanobrevibacter. Enterotypes, which are prevalent constellations of gut microbiome composition, are distinctly distributed over the BSS-scores, with a higher prevalence of Prevotella-enterotyped samples in the looser stool categories (chapters 5 and 6). BSS score has been put forward as an indicative measure of transit time, but also reflects water availability. Both rate of passage and water activity variation are thus potential mechanisms for niche differentiation within the colon ecosystem. By demonstrating - through water activity measurements - that fecal samples provide sufficient unbound water to support the growth of most bacteria, we however showed that the observed effects of stool consistency on colon microbiota composition are unlikely to be a result of water activity variation, but rather represent differences in transit time or other, currently unassessed variables (chapter 7). Furthermore we assessed the effect of inulin supplementation, combining ecosystem-wide microbiome and metabolome profiling techniques, throughout a cross-over intervention aimed at improving constipation in healthy individuals. We demonstrated that the effect of inulin on the fecal microbiota is mainly restricted to changes in Anaerostipes, Bilophila, and Bifidobacterium relative abundances. Regarding fecal metabolites, only dodecanal was found to increase abundance with the inulin intervention. Hence, inulin indeed selectively influences growth of a limited number of colon bacteria, meeting the most debated criterion of the definition of prebiotics. In addition, we found first indications that reduction of Bilophila, a genus containing known pathobionts, is associated with enhanced host wellbeing and could play a role in the inulin-associated prebiotic mechanism (chapter 8). In conclusion, the fecal sampling devices designed during this thesis together with the obtained results regarding covariates of gut microbiome composition will contribute to the development of microbiome research as a clinical and diagnostic field.status: publishe

Water activity does not shape the microbiota in the human colon

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Practical considerations for large-scale gut microbiome studies

First insights on the human gut microbiome have been gained from medium-sized, cross-sectional studies. However, given the modest portion of explained variance of currently identified covariates and the small effect size of gut microbiota modulation strategies, upscaling seems essential for further discovery and characterisation of the multiple influencing factors and their relative contribution. In order to guide future research projects and standardisation efforts, we here review currently applied collection and preservation methods for gut microbiome research. We discuss aspects such as sample quality, applicable omics techniques, user experience and time and cost efficiency. In addition, we evaluate the protocols of a large-scale microbiome cohort initiative, the Flemish Gut Flora Project, to give an idea of perspectives, and pitfalls of large-scale faecal sampling studies. Although cryopreservation can be regarded as the gold standard, freezing protocols generally require more resources due to cold chain management. However, here we show that much can be gained from an optimised transport chain and sample aliquoting before freezing. Other protocols can be useful as long as they preserve the microbial signature of a sample such that relevant conclusions can be drawn regarding the research question, and the obtained data are stable and reproducible over time.status: publishe

Comparisons of gut microbiota profiles in wild-type and gelatinase B/matrix metalloproteinase-9-deficient mice in acute DSS-induced colitis

Gut microbiota help to educate the immune system and a number of involved immune cells were recently characterized. However, specific molecular determinants in these processes are not known, and, reciprocally, little information exists about single host determinants that alter the microbiota. Gelatinase B/matrix metalloproteinase-9 (MMP-9), an innate immune regulator and effector, has been suggested as such a host determinant. In this study, acute colitis was induced in co-housed MMP-9-/- mice (n = 10) and their wild-type (WT) littermates (n = 10) via oral administration of 3% dextran sodium sulfate (DSS) for 7 days followed by 2 days of regular drinking water. Control mice (10 WT and 10 MMP-9-/-) received normal drinking water. Fecal samples were collected at time of sacrifice and immediately frozen at -80 °C. Microbiota analysis was performed using 16S rRNA amplicon sequencing on Illumina MiSeq and taxonomic annotation was performed using the Ribosomal Database Project as reference. Statistical analysis correcting for multiple testing was done using R. No significant differences in clinical or histopathological parameters were found between both genotypes with DSS-induced colitis. Observed microbial richness at genus level and microbiota composition were not significantly influenced by host genotype. In contrast, weight loss, disease activity index, cage, and phenotype did significantly influence the intestinal microbiota composition. After multivariate analysis, cage and phenotype were identified as the sole drivers of microbiota composition variability. In conclusion, changes in fecal microbiota composition were not significantly altered in MMP-9-deficient mice compared to wild-type littermates, but instead were mainly driven by DSS-induced colonic inflammation.status: publishe

Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates

Objective: The assessment of potentially confounding factors affecting colon microbiota composition is essential to the identification of robust microbiome based disease markers. Here, we investigate the link between gut microbiota variation and stool consistency using Bristol Stool Scale classification, which reflects faecal water content and activity, and is considered a proxy for intestinal colon transit time. Design: Through 16S rDNA Illumina profiling of faecal samples of 53 healthy women, we evaluated associations between microbiome richness, Bacteroidetes: Firmicutes ratio, enterotypes, and genus abundance with self-reported, Bristol Stool Scale-based stool consistency. Each sample's microbiota growth potential was calculated to test whether transit time acts as a selective force on gut bacterial growth rates. Results: Stool consistency strongly correlates with all known major microbiome markers. It is negatively correlated with species richness, positively associated to the Bacteroidetes: Firmicutes ratio, and linked to Akkermansia and Methanobrevibacter abundance. Enterotypes are distinctly distributed over the BSS-scores. Based on the correlations between microbiota growth potential and stool consistency scores within both enterotypes, we hypothesise that accelerated transit contributes to colon ecosystem differentiation. While shorter transit times can be linked to increased abundance of fast growing species in Ruminococcaceae-Bacteroides samples, hinting to a washout avoidance strategy of faster replication, this trend is absent in Prevotella-enterotyped individuals. Within this enterotype adherence to host tissue therefore appears to be a more likely bacterial strategy to cope with washout. Conclusions: The strength of the associations between stool consistency and species richness, enterotypes and community composition emphasises the crucial importance of stool consistency assessment in gut metagenome-wide association studies