Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis
Abstract 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....
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202303457 |
| _version_ | 1797373738257219584 |
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| author | Qi‐Wen Wang Ding‐Jia‐Cheng Jia Jia‐Min He Yong Sun Yun Qian Qi‐Wei Ge Ya‐Dong Qi Qing‐Yi Wang Ying‐Ying Hu Lan Wang Yan‐Fei Fang Hui‐Qin He Man Luo Li‐Jun Feng Jian‐Min Si Zhang‐Fa Song Liang‐Jing Wang Shu‐Jie Chen |
| author_facet | Qi‐Wen Wang Ding‐Jia‐Cheng Jia Jia‐Min He Yong Sun Yun Qian Qi‐Wei Ge Ya‐Dong Qi Qing‐Yi Wang Ying‐Ying Hu Lan Wang Yan‐Fei Fang Hui‐Qin He Man Luo Li‐Jun Feng Jian‐Min Si Zhang‐Fa Song Liang‐Jing Wang Shu‐Jie Chen |
| author_sort | Qi‐Wen Wang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-08T18:54:46Z |
| format | Article |
| id | doaj.art-473b7375e8fd4039baa054d5afe189c3 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T18:54:46Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-473b7375e8fd4039baa054d5afe189c32023-12-28T14:55:40ZengWileyAdvanced Science2198-38442023-12-011036n/an/a10.1002/advs.202303457Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid BiosynthesisQi‐Wen Wang0Ding‐Jia‐Cheng Jia1Jia‐Min He2Yong Sun3Yun Qian4Qi‐Wei Ge5Ya‐Dong Qi6Qing‐Yi Wang7Ying‐Ying Hu8Lan Wang9Yan‐Fei Fang10Hui‐Qin He11Man Luo12Li‐Jun Feng13Jian‐Min Si14Zhang‐Fa Song15Liang‐Jing Wang16Shu‐Jie Chen17Department of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology and Hepatology Shenzhen University General Hospital Shenzhen Guangdong 518055 ChinaDepartment of Gastroenterology Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Nutrition Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Nutrition Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Colorectal Surgery Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaDepartment of Gastroenterology Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310058 ChinaAbstract 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.https://doi.org/10.1002/advs.202303457colitismicrobesretinoic acidTh17 |
| spellingShingle | Qi‐Wen Wang Ding‐Jia‐Cheng Jia Jia‐Min He Yong Sun Yun Qian Qi‐Wei Ge Ya‐Dong Qi Qing‐Yi Wang Ying‐Ying Hu Lan Wang Yan‐Fei Fang Hui‐Qin He Man Luo Li‐Jun Feng Jian‐Min Si Zhang‐Fa Song Liang‐Jing Wang Shu‐Jie Chen Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis Advanced Science colitis microbes retinoic acid Th17 |
| title | Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis |
| title_full | Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis |
| title_fullStr | Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis |
| title_full_unstemmed | Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis |
| title_short | Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis |
| title_sort | lactobacillus intestinalis primes epithelial cells to suppress colitis related th17 response by host microbe retinoic acid biosynthesis |
| topic | colitis microbes retinoic acid Th17 |
| url | https://doi.org/10.1002/advs.202303457 |
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