Fatty Acids Guide Gut Immunity

SUMMARY

Immune responses can significantly alter the structure and function of the gut microbiota, leading to rapid transcriptional and metabolic shifts in commensal microbes. However, the host mediators involved in this process and their effects on bacteria remain poorly elucidated. Here, using a flagellin injection model to induce immune activation, the authors identified unsaturated long-chain fatty acids (uLCFAs) as broad modulators that are released into the gut lumen and alter bacterial gene expression. Luminal release of uLCFAs is partially mediated by host phospholipases, including PLA2G5. In response to uLCFAs, commensals such as Blautia trigger the expression of ohyA, encoding oleate hydratase, which converts toxic uLCFAs to non-toxic hydroxy fatty acids with immunomodulatory properties. Remarkably, oral administration of uLCFAs to mice replicates many of the bacterial transcriptional changes induced by flagellin. This molecular loop underscores the sophisticated interactions between host and microbiota and sheds light on how immune responses affect gut commensal functions.

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WHY IS THIS IMPORTANT?

When our immune system reacts, it doesn’t just fight microbes; it also changes the gut environment. This study shows that during inflammation, our body releases long-chain unsaturated fatty acids (uLCFAs) into the intestine. While these fatty acids can be toxic to some bacteria, beneficial microbes like Blautia have developed ways to transform them into harmless hydroxy-fatty acids. Surprisingly, these new molecules can calm down parts of the immune system, reducing inflammation. This research highlights a powerful two-way conversation between the immune system and gut bacteria, with potential implications for diseases like colitis, obesity, and diabetes.

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