Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis

• Published in: Advanced science Vol. 10; no. 36; pp. e2303457 - n/a
• Main Authors: Wang, Qi‐Wen, Jia, Ding‐Jia‐Cheng, He, Jia‐Min, Sun, Yong, Qian, Yun, Ge, Qi‐Wei, Qi, Ya‐Dong, Wang, Qing‐Yi, Hu, Ying‐Ying, Wang, Lan, Fang, Yan‐Fei, He, Hui‐Qin, Luo, Man, Feng, Li‐Jun, Si, Jian‐Min, Song, Zhang‐Fa, Wang, Liang‐Jing, Chen, Shu‐Jie
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.12.2023; John Wiley and Sons Inc; Wiley
• Subjects: Acids; Animals; colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis, Ulcerative - drug therapy; Colon; Disease; E coli; Epithelial Cells - metabolism; Feces; Flow cytometry; Homeostasis; Humans; Inflammation; Inflammatory bowel disease; Lymphocytes; Metabolism; Metabolites; Mice; microbes; Microbiota; Pathology; retinoic acid; Th17; Th17 Cells - metabolism; Tretinoin - metabolism; Tretinoin - pharmacology; Tretinoin - therapeutic use; Vitamin A; retinoic acid; colitis; microbes; Th17
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202303457

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate‐induced colitis in mice. Based on flow cytometry, colitis‐associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell‐null Rag1−/− mice or upon anti‐IL‐17‐A antibody‐treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA‐driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti‐colitis effect in RAR‐α ‐mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA‐SAA1/2‐Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity. By improving retinoic acid synthesis, a novel probiotic L. intestinalis exerts a protective effect against colitis. Retinoic acid triggers epithelial gene alteration, including SAA1, SAA2, and C/EBPA, to downregulate RORγt+ Th17 cells. L. intestinalis and its associated metabolite, retinoic acid, have potential therapeutic effects for suppressing colonic inflammation.