Altered gut microbiome composition in patients with Vogt-Koyanagi-Harada disease

ABSTRACT

Background

Vogt-Koyanagi-Harada (VKH) disease is a multisystemic autoimmune disorder characterized by granulomatous panuveitis. Gut microbiome has been considered to play a role in the pathogenesis of this disease but whether the alternation of gut microbiome was involved is unclear. This study was set up to identify abnormalities of gut microbiome composition in VKH disease.     

Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice

ABSTRACT

Objective

The gut microbiome plays a key role in the development of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. Here we investigate the individual contribution of the pre- and post-transplant gut microbiome to acute GVHD using a well-studied mouse model.     

Gut microbiota regulate tumor metastasis via circRNA/miRNA networks

ABSTRACT

Background

Increasing evidence indicates that gut microbiota plays an important role in cancer progression. However, the underlying mechanism remains largely unknown. Here, we report that broad-spectrum antibiotics (ABX) treatment leads to enhanced metastasis by the alteration of gut microbiome composition.     

Environmental and intrinsic factors shaping gut microbiota composition and diversity and its relation to metabolic health in children and early adolescents: A population-based study

ABSTRACT

Background

Gut microbiota, by influencing multiple metabolic processes in the host, is an important determinant of human health and disease. However, gut dysbiosis associated with metabolic complications shows inconsistent patterns. This is likely driven by factors shaping gut microbial composition that have largely been under-evaluated, at a population level, in school-age children, especially from developing countries.     

Long-term effects of antimicrobial drugs on the composition of the human gut microbiota

ABSTRACT

Introduction

Antimicrobial drugs are known to have effects on the human gut microbiota. We studied the long-term temporal relationship between several antimicrobial drug groups and the composition of the human gut microbiota determined in feces samples.     

Maternal sucralose intake alters gut microbiota of offspring and exacerbates hepatic steatosis in adulthood

ABSTRACT

Background

Nonalcoholic fatty liver disease (NAFLD) is considered to be associated with diet and gut dysbiosis. Excessive sucralose can induce gut dysbiosis and negatively affect host health. Maternal diet shapes the microbial communities of neonate and this effect continues in later life. We aimed to investigate the effects of maternal sucralose (MS) intake on the susceptibility of offspring to hepatic steatosis in adulthood.     

Additional Candida albicans administration enhances the severity of dextran sulfate solution induced colitis mouse model through leaky gut-enhanced systemic inflammation and gut-dysbiosis but attenuated by Lactobacillus rhamnosus L34

ABSTRACT

Candida albicans

is abundant in the human gut mycobiota but this species does not colonize the mouse gastrointestinal tract. C. albicans administration in dextran-sulfate solution (DSS) induced-colitis mouse model (DSS+Candida) might resemble more to human condition, therefore, a DSS colitis model with Candida administration was studied; first, to test the influence of fungi in DSS model and second, to test the efficacy of Lactobacillus rhamnosus L34. We demonstrated serum (1→3)-β-D-glucan (BG) elevation in patients with IBD and endoscopic moderate colitis in clinical remission, supporting the possible influence of gut fungi toward IBD in human. Then, in mouse model, Candida gavage was found to worsen the DSS model indicated by higher mortality rate, more severe colon histology and enhanced gut-leakage (FITC-dextran assay, endotoxemia, serum BG and blood bacterial burdens) but did not affect weight loss and diarrhea. DSS+Candida induced higher pro-inflammatory cytokines both in blood and in intestinal tissue. Worsened systemic pro-inflammatory cytokine responses in DSS+Candida compared with DSS alone was possibly due to the more severe translocation of LPS, BG and bacteria (not fungemia) from gut into systemic circulation. Interestingly, bacteremia from Pseudomonas aeruginosa was more frequently isolated from DSS+Candida than DSS alone. In parallel, P. aeruginosa was also isolated from fecal culture in most of the mice in DSS+Candida group supported by prominent Gammaproteobacteria in fecal microbioata analysis. However, L. rhamnosus L34 attenuated both DSS+Candida and DSS model through the attenuation of gut local inflammation (cytokines and histology), gut-leakage severity, fecal dysbiosis (culture method and microbiome analysis) and systemic inflammation (serum cytokines). In conclusion, gut Candida in DSS model induced fecal bacterial dysbiosis and enhanced leaky-gut induced bacteremia. Probiotic treatment strategy aiming to reduce gut-fungi and fecal dysbiosis could attenuate disease severity. Investigation on gut fungi in patients with IBD is highly interesting.     

Human resident gut microbe Bacteroides thetaiotaomicron regulates colonic neuronal innervation and neurogenic function

ABSTRACT

Background and aims

As the importance of gut–brain interactions increases, understanding how specific gut microbes interact with the enteric nervous system (ENS), which is the first point of neuronal exposure becomes critical. Our aim was to understand how the dominant human gut bacterium Bacteroides thetaiotaomicron (Bt) regulates anatomical and functional characteristics of the ENS.     

Airway microbiota in patients with paediatric cystic fibrosis: Relationship with clinical status

Introduction

New massive sequencing techniques make it possible to determine the composition of airway microbiota in patients with cystic fibrosis (CF). However, the relationship between the composition of lung microbiome and the clinical status of paediatric patients is still not fully understood.

The composition and richness of the gut microbiota differentiate the top Polish endurance athletes from sedentary controls

ABSTRACT

Background

Little data are available on the subject of gut microbiota composition in endurance athletes as well as connections between diet and specific bacteria abundance. However, most studies suggest that athletes’ microbiota undergoes major alterations, which may contribute to increased physical performance. Therefore, we decided to investigate differences in gut microbiota between healthy controls and endurance athletes.     

The Gut Microbiome as a Target for the Treatment of Type 2 Diabetes

Purpose of Review

The objective of this review is to critically assess the contributing role of the gut microbiota in human obesity and type 2 diabetes (T2D).

Recent Findings

Experiments in animal and human studies have produced growing evidence for the causality of the gut microbiome in developing obesity and T2D. The introduction of high-throughput sequencing technologies has provided novel insight into the interpersonal differences in microbiome composition and function.

Summary

The intestinal microbiota is known to be associated with metabolic syndrome and related comorbidities. Associated diseases including obesity, T2D, and fatty liver disease (NAFLD/NASH) all seem to be linked to altered microbial composition; however, causality has not been proven yet. Elucidating the potential causal and personalized role of the human gut microbiota in obesity and T2D is highly prioritized.

     

CODY enables quantitatively spatiotemporal predictions on in vivo gut microbial variability induced by diet intervention

Microbial variations in the human gut are harbored in temporal and spatial heterogeneity, and quantitative prediction of spatiotemporal dynamic changes in the gut microbiota is imperative for development of tailored microbiome-directed therapeutics treatments, e.g. precision nutrition. Given the high-degree complexity of microbial variations, subject to the dynamic interactions among host, microbial, and environmental factors, identifying how microbiota colonize in the gut represents an important challenge. Here we present COmputing the DYnamics of microbiota (CODY), a multiscale framework that integrates species-level modeling of microbial dynamics and ecosystem-level interactions into a mathematical model that characterizes spatial-specific in vivo microbial residence in the colon as impacted by host physiology. The framework quantifies spatiotemporal resolution of microbial variations on species-level abundance profiles across site-specific colon regions and in feces, independent of a priori knowledge. We demonstrated the effectiveness of CODY using cross-sectional data from two longitudinal metagenomics studies—the microbiota development during early infancy and during short-term diet intervention of obese adults. For each cohort, CODY correctly predicts the microbial variations in response to diet intervention, as validated by available metagenomics and metabolomics data. Model simulations provide insight into the biogeographical heterogeneity among lumen, mucus, and feces, which provides insight into how host physical forces and spatial structure are shaping microbial structure and functionality.

Changes in the human gut microbiome composition are connected with development of numerous diseases, like obesity, type-2 diabetes, and immune dysfunction (1–3). Quantitative understanding and predicting how microbial variations are determined are crucial for designing microbiome-directed therapies that target chronic metabolic diseases (4, 5). However, this remains challenging due to the temporal and spatial heterogeneity along the human gut resulting from a dynamic interplay among host, microbial, and environmental conditions (6, 7). Diet is recognized as a controllable and pivotal environmental factor in shaping longitudinal microbial landscape development (8, 9), such as early childhood colonization (10) and long-term adulthood stabilization (11). While profiling of fecal samples enables a snapshot of consequential changes of the fecal microbiota in response to different stimuli, e.g. dietary changes (12–14), it is still far from describing the intrinsic dynamics of how microbiome colonize in the gut. Recently, the spatial heterogeneity of microbial composition between lumen and mucus has been recognized in mice (15, 16), but similar studies in humans is impossible with current techniques. In addition, measurements of absolute abundance profiles are required to correct the artifacts associated with relative abundance that confound revealing the interplay between microbial variations and health (17). Therefore, methods that enable quantifying the absolute, temporal, and spatial variations of in vivo human gut microbiota are needed to understand how to maintain or restore healthy microbiota.Computational models are widely used to decipher microbial complexity and response to perturbations (18). Most existing models have limited usage as they only address specific elements of the multidimensional interaction mechanisms. For example, similarity-based (19) and rule-mining models (20) describe microbial–microbial interactions without considering temporal dependency. The dynamic Bayesian model enables incorporation of directed interactions and longitudinal dataset (21), while reliance on training dataset and difficulties in model selection render these stochastic models confining to specific statistic condition and predictions are therefore not consistent and generalizable (22). The generalized Lotka–Volterra model (18, 23, 24) represents a step forward to simulate dynamics via formulating microbial growth rate as a lumped term, but adherence to assumptions of pairwise interactions-driven community dynamics and constant environment limits their predictive power. Genome-scale models (GEMs) (25) provide a valuable resource for studying structured microbial metabolism. With GEMs, microbial metabolic capacity, microbe–microbe interactions (26–28), microbial–diet interactions (12), and structural changes of two-species cocultures (29) are characterized using flux balance analysis (FBA). With rare exceptions, FBA requires a priori knowledge of metabolite uptake fluxes distributed among community members, with current limitations on these resources, faces challenges with modeling multispecies communities in a dynamic manner (30). Therefore, in adapting a computational framework that can simulate microbiome dynamics along the human gut, one encounters three challenges: 1) endogenously, the intrinsic dynamics not only emerge from the large number of microbiota components but also through the intricate and dynamic ways they interact (31, 32); 2) exogenously, the microbiota is exposed to a series of host–microbe metabolic axes (33), such as colonic physical forces (34), nascent colonization, and nutrient conditions; and 3) spatial structure of the in vivo microbiota localization plays a significant role impacting 1 and 2 (24).Here, we bridge the current theoretical gap by developing a multiscale framework for COmputing the DYnamics of gut microbiota (CODY), which enables identification and quantification of spatiotemporal-specific variations of gut microbiome absolute and relative abundance profiles, without a prior knowledge of microbiome interactions. We evaluated CODY’s performance by comparing model simulations with longitudinal changes in the microbial composition in fecal samples and in plasma metabolomics of two cohorts: 1) long-term development of the gut microbiome in early infancy and 2) short-term variation patterns of the gut microbiome in obese adults experiencing diet intervention. Comparison of model simulations with experimental data demonstrated predictive strength of the CODY modeling framework and hence lays the foundation for performing design of microbiome-directed therapeutics or of precision nutrition based on CODY simulations. The source code of CODY is freely available together with full documentation at https://github.com/JunGeng-Sysbio-Chalmers/CODY1.0_SourceCode.     

Microbiome reduction and endosymbiont gain from a switch in sea urchin life history

Animal gastrointestinal tracts harbor a microbiome that is integral to host function, yet species from diverse phyla have evolved a reduced digestive system or lost it completely. Whether such changes are associated with alterations in the diversity and/or abundance of the microbiome remains an untested hypothesis in evolutionary symbiosis. Here, using the life history transition from planktotrophy (feeding) to lecithotrophy (nonfeeding) in the sea urchin Heliocidaris, we demonstrate that the lack of a functional gut corresponds with a reduction in microbial community diversity and abundance as well as the association with a diet-specific microbiome. We also determine that the lecithotroph vertically transmits a Rickettsiales that may complement host nutrition through amino acid biosynthesis and influence host reproduction. Our results indicate that the evolutionary loss of a functional gut correlates with a reduction in the microbiome and the association with an endosymbiont. Symbiotic transitions can therefore accompany life history transitions in the evolution of developmental strategies.

Animal gastrointestinal tracts contain microbial communities that are integral to host metabolism, immunity, and development (1, 2). Symbioses between animals and their gut microbiome have deep evolutionary origins (1, 2), often exhibit phylosymbiosis (3), and can serve as a physiological buffer to heterogeneous environments (2). Despite the necessity of the gastrointestinal tract and benefits of the gut microbiome (3), species in various phyla have lost a functional digestive system (4, 5). Loss of a functional gut should, in theory, cascade into a reduction in microbial diversity and the loss of diet-induced shifts in microbiome composition. These nutritional shifts may then provide a niche for functionally important endosymbionts, such as the chemoautotrophic bacteria commonly associated with gutless invertebrates (6, 7).Major life history transitions are driven by tradeoffs in reproduction and development that, in turn, impact fitness (8). These tradeoffs are particularly evident in benthic marine invertebrates whose developmental stages broadly group into two alternative nutritional strategies (4, 9). The first—planktotrophy—typically includes the production of a high number of small, energy-poor eggs that develop into larvae with feeding structures used to collect and process exogenous resources required to reach metamorphic competency (4, 9). The second—lecithotrophy—involves the production of fewer large, energy-rich eggs and nonfeeding larvae that undergo metamorphosis without the requirement of external nutrients through feeding (4, 9). Life history transitions between these developmental modes have occurred in several major animal lineages, with rapid evolutionary shifts from planktotrophy to lecithotrophy being well documented in echinoderms (4, 5, 10–13). It is thought that an increase in the eggs energetic content relaxes the selective pressure maintaining the feeding structures (e.g., the larval arms and a functional gastrointestinal tract) and that development to metamorphosis is accelerated once these are lost (5).One of the most comprehensively studied systems for life history transitions among marine invertebrates involves species in the sea urchin genus Heliocidaris. A speciation event ∼5 Mya resulted in two sister species with alternative life history strategies: Heliocidaris tuberculata is planktotrophic while Heliocidaris erythrogramma is lecithotrophic (14). Typical of planktotrophs, H. tuberculata develops from small eggs into feeding larvae that exhibit morphological plasticity in response to food limitation (15), which is correlated with compositional shifts in the microbiome (16, 17). H. erythrogramma, on the other hand, develops from eggs ∼53× to 86× the volume of H. tuberculata (18), lacks the morphological structures required for feeding, and has a reduced, nonfunctional digestive tract (11). This life history switch and heterochronic shift in development (11) corresponds with a rewiring of the gene regulatory network (19), reorganization of cell fates (20), and modification to gametogenesis (21).Here, we compare the bacterial communities of these Heliocidaris species and test two hypotheses. First, we test whether the loss of gut function coincides with a reduction in microbial symbiont diversity, and second, by simulating the natural range in food availability, we also test that the loss in gut function coincides with a loss in diet-related shifts in the microbiome. We report major reductions in microbiome diversity and abundance as well as the absence of bacterial communities correlated with food availability for the lecithotrophic H. erythrogramma. Moreover, we find that this species vertically transmits a Rickettsiales that encodes pathways for the biosynthesis of essential amino acids, proteins with pivotal roles in host reproduction, and enzymes to metabolize diacylglycerol ethers, the major lipid group responsible for the increase in egg size in H. erythrogramma and that is used to fuel growth and development (18, 22).     

Gut commensal derived-valeric acid protects against radiation injuries

ABSTRACT

Background

Hematopoietic and intestinal systems side effects are frequently found in patients who suffered from accidental or medical radiation exposure. In this case, we investigated the effects of gut microbiota produced-valeric acid (VA) on radiation-induced injuries.     

Faecal microbiota signatures of IBD and their relation to diagnosis,disease phenotype,inflammation, treatment escalation and anti-TNF response in a European Multicentre Study (IBD-Character)

Abstract

Method

We examined faecal samples, using the GA-map? Dysbiosis Test, to associate gut microbiota composition with Crohn’s disease (CD) and ulcerative colitis (UC) and to identify markers for future biomarker identification. We conducted a prospective case-control study (EU-ref. no. 305676) in an inception cohort of 324 individuals (64?CD, 84 UC, 116 symptomatic non-IBD controls and 44 healthy controls) across five European centres and examined 54 predetermined bacterial markers. We categorized patients according to the Montreal Classification and calculated the dysbiosis index (DI). Non-parametric tests were used to compare groups and the Bonferroni correction to adjust for multiple comparisons.     

Gut microbiome contributions to altered metabolism in a pig model of undernutrition

The concept that gut microbiome-expressed functions regulate ponderal growth has important implications for infant and child health, as well as animal health. Using an intergenerational pig model of diet restriction (DR) that produces reduced weight gain, we developed a feature-selection algorithm to identify representative characteristics distinguishing DR fecal microbiomes from those of full-fed (FF) pigs as both groups consumed a common sequence of diets during their growth cycle. Gnotobiotic mice were then colonized with DR and FF microbiomes and subjected to controlled feeding with a pig diet. DR microbiomes have reduced representation of genes that degrade dominant components of late growth-phase diets, exhibit reduced production of butyrate, a key host-accessible energy source, and are causally linked to reduced hepatic fatty acid metabolism (β-oxidation) and the selection of alternative energy substrates. The approach described could aid in the development of guidelines for microbiome stewardship in diverse species, including farm animals, in order to support their healthy growth.

Undernutrition afflicts over 200 million children worldwide and accounts for 45% of mortality in children under 5 y (1). Children with acute malnutrition exhibit wasting (impaired ponderal growth), often accompanied by stunting (reduced linear growth), deficits in bone development, neurodevelopment, and immunity, as well as perturbed metabolism (2, 3). Epidemiologic studies indicate that acute malnutrition in children is not due to food insecurity alone and that perturbed gut microbial community development is a contributing factor; children with severe acute malnutrition (SAM) and moderate acute malnutrition (MAM; weight-for-length z-scores are, respectively, 2 to 3 and >3 SDs below World Health Organization mean values) have microbiota that appear “younger” (more immature) compared to those of chronologically aged-matched healthy children (4–6). Studies in gnotobiotic mice colonized with microbiota from healthy and undernourished children have provided evidence that immature microbiota can transmit features of undernutrition (5, 7). These tests of causality inspired development of microbiota-directed complementary foods (MDCFs) designed to repair the microbiota of undernourished children. A controlled feeding study, involving a small group of 12- to 18-mo-old Bangladeshi children with MAM, identified an MDCF formulation that repaired their microbiota; repair was associated with a marked change in their plasma proteome characterized by alterations in levels of key mediators of bone growth, metabolism, immune function, and neurodevelopment toward a healthy state (5). A larger, longer randomized controlled study showed that this MDCF produced a superior effect on ponderal growth compared to a ready-to-use supplementary food even though the caloric density of the MDCF was 20% lower (8).These observations prompted us to examine the influence of the gut microbiome on weight gain in the domestic pig, Sus scrofa domesticus. We focused on this species for several reasons. First, pigs account for ∼35% of global meat intake, second only to poultry (9, 10). Production costs are heavily influenced by how efficiently feed is transformed into body mass, as well as the degree of growth uniformity across animals (11). Second, pigs have been used as a model for studying human nutrition and metabolism because of the many ways in which they are anatomically, physiologically, and metabolically similar to humans (12, 13). Third, most of the commercial pig industry raises animals in highly controlled farming systems engineered to promote efficient and consistent growth phenotypes. These systems typically include phased feeding programs that transition animals from early, more costly, readily digestible, nutrient-rich diets to later, less-expensive diets with less nutrient fortification where energy/nutrient extraction is more dependent on expressed metabolic activities encoded in the gut microbiome. A central premise of the current study is that in order to more fully realize the goal of predictable robust weight gain at affordable prices, additional knowledge is needed regarding codevelopment of the gut microbiome and host; this knowledge could allow diets to be formulated based on greater understanding of which components (features) of the community play key roles in transforming dietary components to products that the animals use to satisfy their growth requirements (14). The environmentally controlled settings for raising pigs provide great opportunities for performing longitudinal studies designed to delineate these interactions between diet, microbiome features, and host physiology. Finally, the need to focus on whether/how the gut microbiome contributes to growth is made more pressing by international mandates to eliminate use of subtherapeutic antibiotics for growth promotion of farm animals because of the spread of antibiotic-resistant organisms (15, 16).In the present study, we developed an algorithm (entropy-based method for microbial ecology research, EMMER), based on the von Neumann entropy calculation from quantum information theory (17, 18), to identify representative characteristics of fecal microbiomes serially sampled from litters of pigs that were or were not subjected to maternal diet restriction (DR) in utero and then provided either ad libitum access to, or restricted amounts of, a sequence of diets commonly given to farm-reared pigs as they complete their growth cycle. A 45% lower weight was attained by DR compared to full-fed (FF) pigs by the third postnatal month and this difference was sustained for the remainder of the 5-mo-long study. DR microbiomes exhibited a significantly reduced representation of genes encoding enzymes involved in the degradation of polysaccharides from dominant components of diets administered after postnatal day 70. These differences in the DR microbiome were associated with diminished fecal levels of butyrate, a major source of host energy, and significant increases in plasma levels of triglycerides, glucogenic amino acids, and urea cycle precursors. Functional features of DR and FF fecal microbiomes, collected during the period of consumption of the corn/soy-rich “finisher” diet (the last given during the feeding program), were subsequently assayed in gnotobiotic mice under controlled feeding conditions where all animals were provided the same amount of the finisher phase pig diet. The results confirmed the reduced capacity of the DR microbiome to generate butyrate. Moreover, mice colonized with the DR microbiome also exhibited reduced fatty acid oxidation in the liver, a metabolic effect that could explain the redirection of amino acids from protein synthesis to replenish hepatic energy reserves in DR pigs. Marrying longitudinal studies of farm animal gut microbiome development and function, conducted in well-engineered farming systems, with gnotobiotic mouse models that incorporate the microbial communities and diets of the farm animals, provides an opportunity to develop an informed set of practices for microbiome husbandry that promotes healthy growth. The results could have substantial economic and societal impact during this time of increasing global food insecurity and when producing sufficient amounts of high-quality protein to feed a rapidly expanding human population is a major challenge (9).     

Gut Microbiome in Obesity,Metabolic Syndrome,and Diabetes

Purpose of Review

Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.

Recent findings

Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation.

Summary

While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.

     

Mikrobiom,Adipositas und Energiestoffwechsel

Background

The gut microbiome has emerged as a key player in the modulation of the immune system and metabolism. Changes in the composition of the gut microbial ecosystems have been reported to be associated with metabolic diseases but also with the development and progression of cardiovascular diseases, inflammatory bowel disease, certain types of cancer and psychiatric diseases.

Objective

The role of the gut microbiome in the pathophysiology of obesity and type 2 diabetes, and treatment approaches based thereon are discussed.

Microbiome and pathophysiology

The pathophysiology in humans is not entirely understood. Studies in mice suggest a strong causal link between changes in the microbiome and the development of metabolic diseases. Potential mechanisms how the microbiome is linked to diseases of the host include signaling through lipopolysaccharides from gram-negative bacteria and interactions with the host immune system, fermentation of indigestible fiber to short chain fatty acids, modulation of bile acids, and bile acid signaling. Interactions between gut microbiota, its products, and the immune system may lead to an increased gut permeability resulting in visceral fat and liver inflammation with subsequent systemic subclinical inflammation (leaky gut hypothesis). Moreover, host-specific factors and environmental factors have been discussed to have a role.

Conclusion

Increasing knowledge in this area could contribute to the treatment of obesity and type 2 diabetes with fecal or targeted microbiota transplantation.

     

Campylobacter concisus is prevalent in the gastrointestinal tract of patients with microscopic colitis

Abstract

Objectives

Microscopic colitis (MC) is potentially induced by an inflammatory reaction to a luminal gut factor. The emerging pathogen Campylobacter concisus is associated with prolonged diarrhoea and subsequently increased risk of MC. We aimed to examine the prevalence of C. concisus in clinical samples from MC patients, analyse the subtypes collagenous colitis (CC) and lymphocytic colitis (LC), and characterise C. concisus isolates from MC patients by genomic sequencing.