Distinct Microbial Communities Trigger Colitis Development upon Intestinal Barrier Damage via Innate or Adaptive Immune Cells

Abstract

SummaryInflammatory 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.

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

“…Also, the FMD treatment in the current study lasts 4 days and is repeated multiple times, compared to the single, water-only fasting lasting between 36–48 hours in previous studies. Notably, Paraprevotellaceae, associated with water-only fasting but not FMD treatment, has been previously regarded as pro-inflammatory in the context of IBD, with one study finding it to be especially enriched in mice with severe colitis (Roy et al, 2017). Another study also found Paraprevotellaceae abundance increased in rats with increased pro-inflammatory cytokines, such as IL-13, in colonic tissue (Shatzkes et al, 2017).…”

CAMISIM: Simulating metagenomes and microbial communities

“…We also provide a multi-sample mouse gut data set for software developers to benchmark against. For 64 16S rRNA samples from the mouse gut [17], we simulated 5 Gb of Illumina and PacBio reads each. The mice were obtained from 12 different vendors and the samples characterized by 16S V4 amplicon sequencing (OTU mapping file in the supplement).…”

“…We demonstrate the usability and utility of CAMISIM with several applications. We generated complex, multi-replicate benchmark data sets from taxonomic profiles of human and mouse gut microbiomes [1,17]. We also simulated thousands of small "minimally challenging metagenomes" to characterize the effect of varying sequencing coverage, evolutionary divergence of genomes, and sequencing error profiles on the popular MEGAHIT [18] and metaSPAdes [19] assemblers.…”

Correlation-based network analysis for biomarkers in obesity

“…Previous studies have also reported on the link between neutrophils and the gut microbiome [18][19][20][21]. A study by Li et al isolated peripheral neutrophils from participants with the aim of identifying and characterising neutrophil-associated microbiomes [22].…”