Gut Microbiota‐Butyrate‐PPARγ Axis Modulates Adipose Regulatory T Cell Population
Abstract Gut microbiota is essential for the function of peripherally‐induced regulatory T (pTreg) cells. However, how commensal bacteria affect thymically derived fat‐resident Treg cells that harbor a unique expression of peroxisome proliferator‐activated receptor (PPAR)‐γ and suppress inflammation...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202411086 |
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| author | Banru Chen Lizhi Guan Chao Wu Yiwen Gong Lei Wu Minchun Zhang Zhiwen Cao Yufei Chen Chengcan Yang Bing Wang Yunqi Li Bin Li Yufang Bi Guang Ning Jiqiu Wang Weiqing Wang Ruixin Liu |
| author_facet | Banru Chen Lizhi Guan Chao Wu Yiwen Gong Lei Wu Minchun Zhang Zhiwen Cao Yufei Chen Chengcan Yang Bing Wang Yunqi Li Bin Li Yufang Bi Guang Ning Jiqiu Wang Weiqing Wang Ruixin Liu |
| author_sort | Banru Chen |
| collection | DOAJ |
| description | Abstract Gut microbiota is essential for the function of peripherally‐induced regulatory T (pTreg) cells. However, how commensal bacteria affect thymically derived fat‐resident Treg cells that harbor a unique expression of peroxisome proliferator‐activated receptor (PPAR)‐γ and suppress inflammation in visceral adipose tissue (VAT), is not well defined. Here it is revealed that microbiota depletion causes a drastic decline in Treg cell population in VAT, particularly those expressing ST2 (ST2+ Treg), which are largely restored after gut microbiome reconstruction. Mechanistically, gut microbiota‐derived butyrate increases VAT ST2+ Treg cells through binding PPARγ. Butyrate supplementation and high fiber diet increase VAT ST2+ Treg population in obese mice, and ameliorated glucose tolerance and visceral inflammation. Furthermore, human omental adipose Treg cells show positive correlation with fecal butyrate and certain butyrate‐producing microbes. This study identifies the critical role of gut microbiota‐butyrate‐PPARγ axis in maintaining VAT Treg population, pinpointing a potential approach to augment VAT Treg population and ameliorate inflammation. |
| format | Article |
| id | doaj-art-a10cbe4c23594897a72ff15e070dc022 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-a10cbe4c23594897a72ff15e070dc0222025-08-20T03:20:10ZengWileyAdvanced Science2198-38442025-05-011220n/an/a10.1002/advs.202411086Gut Microbiota‐Butyrate‐PPARγ Axis Modulates Adipose Regulatory T Cell PopulationBanru Chen0Lizhi Guan1Chao Wu2Yiwen Gong3Lei Wu4Minchun Zhang5Zhiwen Cao6Yufei Chen7Chengcan Yang8Bing Wang9Yunqi Li10Bin Li11Yufang Bi12Guang Ning13Jiqiu Wang14Weiqing Wang15Ruixin Liu16Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of General Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine 639 Zhizaoju Road Shanghai 200011 ChinaDepartment of General Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine 639 Zhizaoju Road Shanghai 200011 ChinaShanghai Institute of Hematology State Key Laboratory of Medical Genomics National Research Center for Translational Medicine at Shanghai Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 ChinaDepartment of Immunology and Microbiology Shanghai Institute of Immunology Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaDepartment of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 ChinaAbstract Gut microbiota is essential for the function of peripherally‐induced regulatory T (pTreg) cells. However, how commensal bacteria affect thymically derived fat‐resident Treg cells that harbor a unique expression of peroxisome proliferator‐activated receptor (PPAR)‐γ and suppress inflammation in visceral adipose tissue (VAT), is not well defined. Here it is revealed that microbiota depletion causes a drastic decline in Treg cell population in VAT, particularly those expressing ST2 (ST2+ Treg), which are largely restored after gut microbiome reconstruction. Mechanistically, gut microbiota‐derived butyrate increases VAT ST2+ Treg cells through binding PPARγ. Butyrate supplementation and high fiber diet increase VAT ST2+ Treg population in obese mice, and ameliorated glucose tolerance and visceral inflammation. Furthermore, human omental adipose Treg cells show positive correlation with fecal butyrate and certain butyrate‐producing microbes. This study identifies the critical role of gut microbiota‐butyrate‐PPARγ axis in maintaining VAT Treg population, pinpointing a potential approach to augment VAT Treg population and ameliorate inflammation.https://doi.org/10.1002/advs.202411086butyratefibergut microbiotaPPARγST2Treg |
| spellingShingle | Banru Chen Lizhi Guan Chao Wu Yiwen Gong Lei Wu Minchun Zhang Zhiwen Cao Yufei Chen Chengcan Yang Bing Wang Yunqi Li Bin Li Yufang Bi Guang Ning Jiqiu Wang Weiqing Wang Ruixin Liu Gut Microbiota‐Butyrate‐PPARγ Axis Modulates Adipose Regulatory T Cell Population Advanced Science butyrate fiber gut microbiota PPARγ ST2 Treg |
| title | Gut Microbiota‐Butyrate‐PPARγ Axis Modulates Adipose Regulatory T Cell Population |
| title_full | Gut Microbiota‐Butyrate‐PPARγ Axis Modulates Adipose Regulatory T Cell Population |
| title_fullStr | Gut Microbiota‐Butyrate‐PPARγ Axis Modulates Adipose Regulatory T Cell Population |
| title_full_unstemmed | Gut Microbiota‐Butyrate‐PPARγ Axis Modulates Adipose Regulatory T Cell Population |
| title_short | Gut Microbiota‐Butyrate‐PPARγ Axis Modulates Adipose Regulatory T Cell Population |
| title_sort | gut microbiota butyrate pparγ axis modulates adipose regulatory t cell population |
| topic | butyrate fiber gut microbiota PPARγ ST2 Treg |
| url | https://doi.org/10.1002/advs.202411086 |
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