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Gut microbial fatty acid isomerization modulates intraepithelial T cells
Xinyang Song1,2, Haohao Zhang3, Yanbo Zhang4
1State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. xinyang.song@sibcb.ac.cn.
Nature
|June 28, 2023
Summary
Gut bacteria and diet create fatty acid isomers (CLAs) that regulate immune cells in the small intestine. These CLAs are crucial for maintaining gut immunological homeostasis and host survival.
Area of Science:
- Microbiology
- Immunology
- Metabolism
Background:
- The gut microbiome metabolizes dietary components into bioactive molecules.
- Dietary fats, specifically free fatty acids (FFAs), are absorbed in the small intestine.
- Gut bacteria modify unsaturated fatty acids (FAs), like linoleic acid (LA), into isomers with metabolic and anticarcinogenic roles.
Purpose of the Study:
- To investigate the impact of the diet-microorganism FA isomerization network on the host's mucosal immune system.
- To elucidate the role of conjugated linoleic acids (CLAs) in modulating specific immune cell populations.
Main Methods:
- Utilized gnotobiotic mice to study the effects of specific gut symbionts and FA isomerization pathways.
- Genetically modified gut symbionts to abolish FA isomerization pathways.
- Administered CLAs and analyzed the levels of CD4+CD8αα+ intraepithelial lymphocytes (IELs).
- Investigated the role of hepatocyte nuclear factor gamma (HNF4γ) in CLA-mediated immune cell development.
Main Results:
- Dietary and microbial factors influence gut CLA levels.
- CLAs modulate a distinct population of CD4+CD8αα+ IELs in the small intestine.
- Abolishing FA isomerization pathways in gut symbionts reduced CD4+CD8αα+ IEL numbers.
- Restoration of CLAs increased CD4+CD8αα+ IELs, dependent on HNF4γ.
- HNF4γ facilitates CD4+CD8αα+ IEL development via interleukin-18 signaling.
- HNF4γ deficiency in T cells leads to mortality from intestinal infections.
Conclusions:
- Bacterial FA metabolic pathways, specifically CLA production, play a critical role in regulating host intraepithelial immunological homeostasis.
- The interplay between dietary fats, microbial metabolism, and host immunity is essential for maintaining gut health and preventing infection.
