Rheumatoid arthritis (RA) has been associated with a relative expansion of faecal Prevotellaceae. To determine the microbiome composition and prevalence of
spp. in a group of individuals at increased ...risk for RA, but prior to the development of the disease.
In an ongoing cohort study of first-degree relatives (FDRs) of patients with RA, we identified 'FDR controls', asymptomatic and without autoantibodies, and individuals in pre-clinical RA stages, who had either developed anticitrullinated peptide antibodies or rheumatoid factor positivity and/or symptoms and signs associated with possible RA. Stool sampling and culture-independent microbiota analyses were performed followed by descriptive statistics and statistical analyses of community structures.
A total of 133 participants were included, of which 50 were categorised as 'FDR controls' and 83 in 'pre-clinical RA stages'. The microbiota of individuals in 'pre-clinical RA stages' was significantly altered compared with FDR controls. We found a significant enrichment of the bacterial family Prevotellaceae, particularly
spp., in the 'pre-clinical RA' group (p=0.04).
spp. enrichment in individuals in pre-clinical stages of RA, before the onset of RA, suggests a role of intestinal dysbiosis in the development of RA.
Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut ...microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4
effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8
effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia, and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.
Computational methods are key in microbiome research, and obtaining a quantitative and unbiased performance estimate is important for method developers and applied researchers. For meaningful ...comparisons between methods, to identify best practices and common use cases, and to reduce overhead in benchmarking, it is necessary to have standardized datasets, procedures and metrics for evaluation. In this tutorial, we describe emerging standards in computational meta-omics benchmarking derived and agreed upon by a larger community of researchers. Specifically, we outline recent efforts by the Critical Assessment of Metagenome Interpretation (CAMI) initiative, which supplies method developers and applied researchers with exhaustive quantitative data about software performance in realistic scenarios and organizes community-driven benchmarking challenges. We explain the most relevant evaluation metrics for assessing metagenome assembly, binning and profiling results, and provide step-by-step instructions on how to generate them. The instructions use simulated mouse gut metagenome data released in preparation for the second round of CAMI challenges and showcase the use of a repository of tool results for CAMI datasets. This tutorial will serve as a reference for the community and facilitate informative and reproducible benchmarking in microbiome research.
Prevotella spp. are a dominant bacterial genus within the human gut. Multiple Prevotella spp. co-exist in some individuals, particularly those consuming plant-based diets. Additionally, Prevotella ...spp. exhibit variability in the utilization of diverse complex carbohydrates. To investigate the relationship between Prevotella competition and diet, we isolated Prevotella species from the mouse gut, analyzed their genomes and transcriptomes in vivo, and performed competition experiments between species in mice. Diverse dominant Prevotella species compete for similar metabolic niches in vivo, which is linked to the upregulation of specific polysaccharide utilization loci (PULs). Complex plant-derived polysaccharides are required for Prevotella spp. expansion, with arabinoxylans having a prominent impact on species abundance. The most dominant Prevotella species encodes a specific tandem-repeat trsusC/D PUL that enables arabinoxylan utilization and is conserved in human Prevotella copri strains, particularly among those consuming a vegan diet. These findings suggest that efficient (arabino)xylan-utilization is a factor contributing to Prevotella dominance.
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•Metagenomics and culturomics characterization of Prevotella spp. in the mouse gut•Distinct Prevotella spp. compete in vivo for similar plant-derived polysaccharides•A dominant Prevotella strain encodes a specific PUL enabling arabinoxylan utilization•Similar genetic features are found in human Prevotella copri strains enriched in vegans
Prevotella are among the most dominant bacteria found in the gut. Galvez et al. identify Prevotella species in the mouse gut and examine how one dominant species outcompetes commensal bacteria, including other Prevotella species, by encoding specific polysaccharide utilization loci (PULs), notably those enabling arabinoxylan utilization.
The composition of the intestinal microbiota influences the outcome of enteric infections in human and mice. However, the role of specific members and their metabolites contributing to disease ...severity is largely unknown. Using isogenic mouse lines harboring distinct microbiota communities, we observed highly variable disease kinetics of enteric Citrobacter rodentium colonization after infection. Transfer of communities from susceptible and resistant mice into germ-free mice verified that the varying susceptibilities are determined by microbiota composition. The strongest differences in colonization were observed in the cecum and could be maintained in vitro by coculturing cecal bacteria with C. rodentium. Cohousing of animals as well as the transfer of cultivable bacteria from resistant to susceptible mice led to variable outcomes in the recipient mice. Microbiome analysis revealed that a higher abundance of butyrate-producing bacteria was associated with the resistant phenotype. Quantification of short-chain fatty acid (SCFA) levels before and after infection revealed increased concentrations of acetate, butyrate and propionate in mice with delayed colonization. Addition of physiological concentrations of butyrate, but not of acetate and/or propionate strongly impaired growth of C. rodentium in vitro. In vivo supplementation of susceptible, antibiotic-treated and germ-free mice with butyrate led to the same level of protection, notably only when cecal butyrate concentration reached a concentration higher than 50 nmol/mg indicating a critical threshold for protection. In the recent years, commensal-derived primary and secondary bacterial metabolites emerged as potent modulators of hosts susceptibility to infection. Our results provide evidence that variations in SCFA production in mice fed fibre-rich chow-based diets modulate susceptibility to colonization with Enterobacteriaceae not only in antibiotic-disturbed ecosystems but even in undisturbed microbial communities. These findings emphasise the need for microbiota normalization across laboratory mouse lines for infection experiments with the model-pathogen C. rodentium independent of investigations of diet and antibiotic usage.
Inflammatory bowel disease comprises a group of heterogeneous diseases characterized by chronic and relapsing mucosal inflammation. Alterations in microbiota composition have been proposed ...to contribute to disease development, but no uniform signatures have yet been identified. Here, we compare the ability of a diverse set of microbial communities to exacerbate intestinal inflammation after chemical damage to the intestinal barrier. Strikingly, genetically identical wild-type mice differing only in their microbiota composition varied strongly in their colitis susceptibility. Transfer of distinct colitogenic communities in gene-deficient mice revealed that they triggered disease via opposing pathways either independent or dependent on adaptive immunity, specifically requiring antigen-specific CD4+ T cells. Our data provide evidence for the concept that microbial communities may alter disease susceptibility via different immune pathways despite eventually resulting in similar host pathology. This suggests a potential benefit for personalizing IBD therapies according to patient-specific microbiota signatures.
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•Gut microbiota composition modulates colitis severity in immunocompetent hosts•Colitogenic microbiota drive colitis via innate or adaptive immunity•Distinct microbiota members induce pathogenic CD4+ T cells to drive colitis
Alterations in the microbiota contribute to the development of intestinal inflammation. Roy et al. demonstrate that distinct intestinal microbial communities cause colitis via opposing effector mechanisms independent or dependent on adaptive immunity. Their findings suggest that personalized immunomodulatory treatment according to distinct microbial signatures may be beneficial for IBD patients.
As the gut microbiota contributes to metabolic health, it is important to determine specific diet-microbiota interactions that influence host metabolism. Bile acids and dietary fat source can alter ...phenotypes of diet-induced obesity, but the interplay with intestinal microorganisms is unclear. Here, we investigated metabolic consequences of diets enriched in primary bile acids with or without addition of lard or palm oil, and studied gut microbiota structure and functions in mice.
In combination with bile acids, dietary lard fed to male C57BL/6N mice for a period of 8 weeks enhanced fat mass accumulation in colonized, but not in germ-free mice when compared to palm oil. This was associated with impaired glucose tolerance, lower fasting insulin levels, lower counts of enteroendocrine cells, fatty liver, and elevated amounts of hepatic triglycerides, cholesteryl esters, and monounsaturated fatty acids. Lard- and bile acid-fed mice were characterized by shifts in dominant gut bacterial communities, including decreased relative abundances of Lachnospiraceae and increased occurrence of Desulfovibrionaceae and the species Clostridium lactatifermentans and Flintibacter butyricus. Metatranscriptomic analysis revealed shifts in microbial functions, including lipid and amino acid metabolism.
Caution is required when interpreting data from diet-induced obesity models due to varying effects of dietary fat source. Detrimental metabolic consequences of a diet enriched with lard and primary bile acids were dependent on microbial colonization of the host and were linked to hepatic lipid rearrangements and to alterations of dominant bacterial communities in the cecum.
Abstract
With viral infections, multiple related viral strains are often present due to coinfection or within-host evolution. We describe Haploflow, a deBruijn graph-based assembler for de novo ...genome assembly of viral strains from mixed sequence samples using a novel flow algorithm. We assess Haploflow across multiple benchmark data sets of increasing complexity, showing that Haploflow is faster and more accurate than viral haplotype assemblers and generic metagenome assemblers not aiming to reconstruct strains. We show Haploflow reconstructs viral strain genomes from patient HCMV samples and SARS-CoV-2 wastewater samples identical to clinical isolates.
The Segatella copri (formerly Prevotella copri) complex (ScC) comprises taxa that are key members of the human gut microbiome. It was previously described to contain four distinct phylogenetic ...clades. Combining targeted isolation with large-scale metagenomic analysis, we defined 13 distinct Segatella copri-related species, expanding the ScC complex beyond four clades. Complete genome reconstruction of thirteen strains from seven species unveiled the presence of genetically diverse large circular extrachromosomal elements. These elements are consistently present in most ScC species, contributing to intra- and inter-species diversities. The nine species-level clades present in humans display striking differences in prevalence and intra-species genetic makeup across human populations. Based on a meta-analysis, we found reproducible associations between members of ScC and the male sex and positive correlations with lower visceral fat and favorable markers of cardiometabolic health. Our work uncovers genomic diversity within ScC, facilitating a better characterization of the human microbiome.
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•Segatella copri (formerly Prevotella copri) complex includes 13 distinct species•Large extrachromosomal elements contribute to ScC intra- and inter-species diversities•ScC presents a genetic structure linked to geographic origin and lifestyle•ScC is associated with males, low visceral fat, and improved glucose responses
Prevalent human gut commensal bacteria feature a hidden variability hampering molecular and clinical studies. Blanco-Míguez et al. utilize cultivation-dependent and cultivation-independent approaches to describe the Segatella copri complex (ScC). They identify that ScC members contain distinct genomic elements and content as well as display variable association to host phenotypes.
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