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- W4313366382 abstract "Abstract Microbiome-wide association studies have established that numerous diseases are associated with changes in the microbiota. These studies typically generate a long list of commensals implicated as biomarkers of disease, with no clear relevance to disease pathogenesis. If the field is to move beyond correlations and begin to address causation, an effective system is needed for refining this catalog of differentially abundant microbes and allow for mechanistic studies. We demonstrate that triangulation of microbe–phenotype relationships is an effective method for reducing the noise in microbiota studies and enabling identification of causal microbes. We found that gnotobiotic mice harboring different microbial communities exhibited differential survival in a colitis model. Co-housing of these mice generated animals that had hybrid microbiotas and displayed intermediate susceptibility to colitis. Mapping of microbe–phenotype relationships in parental mouse strains and in mice with hybrid microbiotas identified the bacterial family Lachnospiraceae as a correlate for protection from disease. Using directed microbial culture techniques, we discovered Clostridium immunis, a novel bacterial species, that—when administered to colitis-prone mice—protected them against colitis-associated death. To demonstrate its generalizability, we used our approach to identify 2 bacteria that induce intestinal expression of an antimicrobial peptide. Thus, we have used microbe–phenotype triangulation to move beyond the standard correlative microbiome study and identify causal microbes for 2 distinct phenotypes. Identification of disease-modulating commensals by our approach may also be applicable to human microbiome studies." @default.
- W4313366382 created "2023-01-06" @default.
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- W4313366382 date "2018-05-01" @default.
- W4313366382 modified "2023-09-28" @default.
- W4313366382 title "Moving beyond microbiome-wide associations to causal microbe identification" @default.
- W4313366382 doi "https://doi.org/10.4049/jimmunol.200.supp.53.7" @default.
- W4313366382 hasPublicationYear "2018" @default.
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