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Researchers engineered a minimal two-bacteria consortium to investigate how the secondary bile acid isodeoxycholic acid (isoDCA) regulates intestinal immunity. By genetically modifying Ruminococcus gnavus to eliminate isoDCA production and pairing it with Peptacetobacter hiranonis, they created a controlled system that could toggle isoDCA production on or off. The study demonstrates that isoDCA induces regulatory T cells in the colon through specific receptors (TGR5 and FXR), and that bacteria producing isoDCA protected mice against experimental colitis by modulating the microbiome and reducing inflammation.
Why it matters
This work provides a novel experimental approach to study how specific bacterial metabolites influence immune responses and offers potential therapeutic strategies for inflammatory bowel diseases. The engineered bacterial consortium could be developed into a targeted probiotic treatment for conditions involving intestinal inflammation.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Modern lifestyle factors have altered gut microbiota composition and function. Bacteria in the Clostridia class modulate mucosal immune responses through various mechanisms including production of secondary bile acids (SBA). Here, we present a novel system to study how the SBA isodeoxycholic acid (isoDCA) regulates host immunity. Through targeted mutagenesis of bile acid epimerization genes, we engineered Ruminococcus gnavus to ablate isoDCA production. Combining R. gnavus (WT or KO) with Peptacetobacter hiranonis created a two-member consortium that toggles isoDCA production on or off while keeping all other variables constant. Using this system, we demonstrate that isoDCA induces colonic lamina propria ROR{gamma}tFoxp3 regulatory T cells (pTregs) through a mechanism requiring both the Takeda G protein-coupled receptor 5 (TGR5) and the Farnesoid X receptor (FXR). Engraftment of this isoDCA+ consortium protected against colitis in an adoptive T cell transfer model by reshaping the microbiota and suppressing host inflammation.
Source: An engineered Clostridial mini consortium modulates intestinal inflammation