Summary
Background
Intestinal bacteria produce metabolites and by‐products necessary for homeostasis. Imbalance in this equilibrium is linked to multiple pathologies including inflammatory bowel ...disease (IBD). The role of the gut microbiota in determining treatment response is becoming apparent, and may act as biomarker for efficacy.
Aim
To describe knowledge about the intestinal microbiota on disease severity and treatment outcomes in IBD
Methods
Descriptive review using PubMed to identify literature on the intestinal microbiota in IBD
Results
Severe IBD has a less diverse microbiota with fewer commensal microbiota communities and more opportunistic pathogenic bacteria originating from the oral cavity or respiratory tract. IBD treatments can alter gut microbiota composition, but in vitro/in vivo studies are needed to prove causation. A diversification of the microbiota is observed during remission. Patients with a more diverse baseline microbiome and higher microbial diversity show better response to anti‐tumour necrosis factor‐α, vedolizumab and ustekinumab therapy. Higher abundance of short chain fatty acid‐producing bacteria, fewer mucus‐colonising bacteria and lower abundance of pro‐inflammatory bacteria have also been associated with a favourable outcome. Predictive models, based on a combination of microbiota, clinical data and serological markers, have good accuracy for treatment outcome and disease severity.
Conclusion
The intestinal microbiota in IBD carries a set of promising biomarkers of disease activity and prediction of therapeutic outcome. Current insights may also help in designing microbiota modulation strategies to improve outcomes in IBD.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
During the past decade, meta-omics approaches have revolutionized microbiology, allowing for a cultivation-free assessment of the composition and functional properties of entire microbial ecosystems. ...On the one hand, a phylogenetic and functional interpretation of such data relies on accumulated genetic, biochemical, metabolic, and phenotypic characterization of microbial variation. On the other hand, the increasing availability of extensive microbiome data sets and corresponding metadata provides a vast, underused resource for the microbiology field as a whole. To demonstrate the potential for integrating big data into a functional microbiology workflow, we review literature on trimethylamine (TMA), a microbiota-generated metabolite linked to atherosclerosis development. Translating recently elucidated microbial pathways resulting in TMA production into genomic orthologs, we demonstrate how to mine for their presence in public (meta-) genomic databases and link findings to associated metadata. Reviewing pathway abundance in public data sets shows that TMA production potential is associated with symptomatic atherosclerosis and allows identification of currently uncharacterized TMA-producing bacteria.
Contrary to the long-standing prerequisite of inducing selective (ie, bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a ...comprehensive characterisation of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (gas chromatography mass spectrometry) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and faecal metabolites profiles.
Faecal samples collected during a double-blind, randomised, cross-over intervention study set up to assess the effect of inulin consumption on stool frequency in healthy adults with mild constipation were analysed. Faecal microbiota composition and metabolite profiles were linked to the study's clinical outcome as well as to quality-of-life measurements recorded.
While faecal metabolite profiles were not significantly altered by inulin consumption, our analyses did detect a modest effect on global microbiota composition and specific inulin-induced changes in relative abundances of
,
and
were identified. The observed decrease in
abundances following inulin consumption was associated with both softer stools and a favourable change in constipation-specific quality-of-life measures.
Ecosystem-wide analysis of the effect of a dietary intervention with prebiotic inulin-type fructans on the colon microbiota revealed that this effect is specifically associated with three genera, one of which (
) representing a promising novel target for mechanistic research.
NCT02548247.
The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune ...diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research.
Current sequencing-based analyses of faecal microbiota quantify microbial taxa and metabolic pathways as fractions of the sample sequence library generated by each analysis. Although these relative ...approaches permit detection of disease-associated microbiome variation, they are limited in their ability to reveal the interplay between microbiota and host health. Comparative analyses of relative microbiome data cannot provide information about the extent or directionality of changes in taxa abundance or metabolic potential. If microbial load varies substantially between samples, relative profiling will hamper attempts to link microbiome features to quantitative data such as physiological parameters or metabolite concentrations. Saliently, relative approaches ignore the possibility that altered overall microbiota abundance itself could be a key identifier of a disease-associated ecosystem configuration. To enable genuine characterization of host-microbiota interactions, microbiome research must exchange ratios for counts. Here we build a workflow for the quantitative microbiome profiling of faecal material, through parallelization of amplicon sequencing and flow cytometric enumeration of microbial cells. We observe up to tenfold differences in the microbial loads of healthy individuals and relate this variation to enterotype differentiation. We show how microbial abundances underpin both microbiota variation between individuals and covariation with host phenotype. Quantitative profiling bypasses compositionality effects in the reconstruction of gut microbiota interaction networks and reveals that the taxonomic trade-off between Bacteroides and Prevotella is an artefact of relative microbiome analyses. Finally, we identify microbial load as a key driver of observed microbiota alterations in a cohort of patients with Crohn's disease, here associated with a low-cell-count Bacteroides enterotype (as defined through relative profiling).
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin ...resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
8.
Population-level analysis of gut microbiome variation Falony, Gwen; Joossens, Marie; Vieira-Silva, Sara ...
Science (American Association for the Advancement of Science),
04/2016, Volume:
352, Issue:
6285
Journal Article
Peer reviewed
Fecal microbiome variation in the average, healthy population has remained under-investigated. Here, we analyzed two independent, extensively phenotyped cohorts: the Belgian Flemish Gut Flora Project ...(FGFP; discovery cohort; N = 1106) and the Dutch LifeLines-DEEP study (LLDeep; replication; N = 1135). Integration with global data sets (N combiend = 3948) revealed a 14-genera core microbiota, but the 664 identified genera still underexplore total gut diversity. Sixty-nine clinical and questionnaire-based covariates were found associated to microbiota compositional variation with a 92% replication rate. Stool consistency showed the largest effect size, whereas medication explained largest total variance and interacted with other covariate-microbiota associations. Early-life events such as birth mode were not reflected in adult microbiota composition. Finally, we found that proposed disease marker genera associated to host covariates, urging inclusion of the latter in study design.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Deep sequencing of the gut microbiomes of 1135 participants from a Dutch population-based cohort shows relations between the microbiome and 126 exogenous and intrinsic host factors, including 31 ...intrinsic factors, 12 diseases, 19 drug groups, 4 smoking categories, and 60 dietary factors. These factors collectively explain 18.7% of the variation seen in the interindividual distance of microbial composition. We could associate 110 factors to 125 species and observed that fecal chromogranin A (CgA), a protein secreted by enteroendocrine cells, was exclusively associated with 61 microbial species whose abundance collectively accounted for 53% of microbial composition. Low CgA concentrations were seen in individuals with a more diverse microbiome. These results are an important step toward a better understanding of environment-diet-microbe-host interactions.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Introduction: End-stage liver disease (ESLD) is the advanced phase of most liver diseases. The cure is liver transplantation (LT), only available for a minority of patients. This review summarizes ...the evidence regarding palliative care (PC) in ESLD patients awaiting LT. Methods: Review of the literature available in Medline, Scopus and Web of Knowledge, with keywords ESLD and PC. Results: Fifteen of the 230 articles reviewed met the inclusion criteria. Ten main themes were addressed: symptom burden; perspectives of life-sustaining treatment and comfort for patients, families and health professionals; goals of care discussions; patient and family needs; quality of life; PC and survival; referral to PC, barriers and opportunities; integration of PC; outpatient care and cost-effectiveness analysis. The referral of patients to PC was only evaluated in a few studies, all of which reported low referral rates. Better knowledge of how PC professionals can support other professionals was considered important, and also better ways to integrate PC were considered essential. Conclusion: ESLD patients awaiting LT have a significant need for PC and, despite the insufficient response, were reported to benefit from this type of care. Future research is essential to determine the means to overcome barriers and better integrate PC for ESLD patients awaiting LT.
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