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Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis

ABSTRACT: GUT103 and GUT108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients; they address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. Systematic colonization experiments in colitis mouse models were performed to test their therapeutic effects. Targeted fecal metabolomics data uploaded here of bile acids, short-chain fatty acids, and tryptophan metabolites provides a unique metabolome perspective for evaluation of the therapeutic potential of GUT103 and GUT108.

ORGANISM(S): Mus Musculus

TISSUE(S): Feces

SUBMITTER: Yunjia Lai

PROVIDER: ST001748 | MetabolomicsWorkbench | Thu Apr 22 00:00:00 BST 2021

REPOSITORIES: MetabolomicsWorkbench

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Project description:Background and aims. The etiopathology of inflammatory bowel diseases is still poorly understood. To date, only few little data are available on the microbiota composition in ulcerative colitis (UC), representing a major subform of inflammatory bowel diseases. Currently, one of the main challenges is to unravel the interactions between genetics and environmental factors in the onset or during the progression and maintenance of the disease. The aim of the present study was to analyse twin pairs discordant for UC for both gut microbiota dysbiosis and host expression profiles at a mucosal level and to get insight into the functional genomic crosstalk between microbiota and mucosal epithelium in vivo. Methods. Biopsies were sampled from the sigmoid colon of both healthy and diseased siblings from UC discordant twin pairs but also from healthy twins. Microbiota profiles were assessed by 16S rDNA libraries while mRNA expression profiles were analysed from the same volunteers using Affymetrix microarrays. Results. UC patients showed a dysbiotic microbiota with lower diversity and more species belonging to Actinobacteria and Proteobacteria phyla. On the contrary, their healthy siblingsM-bM-^@M-^Y microbiota contained more bacteria from the Lachnospiracea and Ruminococcaceae family than did healthy individuals . Sixty-three host transcripts significantly correlated with bacterial genera in healthy individuals whereas only 43 and 32 correlated with bacteria in healthy and UC siblings from discordant pairs, respectively. Several transcripts related to oxidative and immune responses were differentially expressed between unaffected and UC siblings. Conclusion. A loss of crosstalk between gut microbiota and host was highlighted in UC patients. This defect was also striking in healthy siblings from discordant pairs, as was the lower biodiversity within the microbiota. Our results suggest disease-relevant interactions between host transcriptome and microbiota. Moreover, unusual aerobic bacteria were noticed in UC mucosal microbiota, whereas healthy siblings from discordant pairs had higher percentages of potentially beneficialusual commensal bacterial species. Paired samples (twins) were analyzed to obtain data independent of genetic variation

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Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis

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