Bifidobacterium pseudolongum‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 Pathway
Abstract Carvacrol and thymol (CAT) have been widely recognized for their antimicrobial and anti‐inflammatory properties, yet their specific effects on colitis and the mechanisms involved remain insufficiently understood. This study establishes a causative link between CAT administration and colitis...
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Wiley
2024-11-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406917 |
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| author | Ke Zhang Yangbin Xu Yining Zheng Ting Zhang Yujiang Wu Yiting Yan Yu Lei Xi Cao Xiaolong Wang Frances Yan Zhaomin Lei Daniel Brugger Yulin Chen Lu Deng Yuxin Yang |
| author_facet | Ke Zhang Yangbin Xu Yining Zheng Ting Zhang Yujiang Wu Yiting Yan Yu Lei Xi Cao Xiaolong Wang Frances Yan Zhaomin Lei Daniel Brugger Yulin Chen Lu Deng Yuxin Yang |
| author_sort | Ke Zhang |
| collection | DOAJ |
| description | Abstract Carvacrol and thymol (CAT) have been widely recognized for their antimicrobial and anti‐inflammatory properties, yet their specific effects on colitis and the mechanisms involved remain insufficiently understood. This study establishes a causative link between CAT administration and colitis mitigation, primarily through the enhancement of Bifidobacterium pseudolongum abundance in the colon. This increase promotes the production of secondary bile acids, particularly hyodeoxycholic acid (HDCA) and 12‐ketodeoxycholic acid (12‐KCAC), which exert anti‐inflammatory effects. Notably, CAT does not alleviate colitis symptoms in germ‐free mice, indicating the necessity of gut microbiota. This research uncovers a novel regulatory mechanism where HDCA and 12‐KCAC inhibit colonic inflammation by reducing the expression of transmembrane guanylate cyclase 1A in the colonic epithelium. This downregulation elevates intracellular Ca2+ and cGMP levels, activating protein kinase G (PKG). Activated PKG subsequently suppresses the mTOR signaling pathway, thereby ameliorating dextran sulfate sodium (DSS)‐induced colonic damage. These findings highlight potential metabolites and therapeutic targets for preventing and treating colitis. Bifidobacterium pseudolongum, HDCA, and 12‐KCAC emerge as promising candidates for therapeutic interventions in colitis and related disorders characterized by impaired tight junction function. |
| format | Article |
| id | doaj-art-95900ba8ae984e2fafccd7e6a6d3a96a |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-95900ba8ae984e2fafccd7e6a6d3a96a2024-11-20T19:25:40ZengWileyAdvanced Science2198-38442024-11-011143n/an/a10.1002/advs.202406917Bifidobacterium pseudolongum‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 PathwayKe Zhang0Yangbin Xu1Yining Zheng2Ting Zhang3Yujiang Wu4Yiting Yan5Yu Lei6Xi Cao7Xiaolong Wang8Frances Yan9Zhaomin Lei10Daniel Brugger11Yulin Chen12Lu Deng13Yuxin Yang14College of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaCollege of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaCollege of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaCollege of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaInstitute of Animal Sciences Tibet Academy of Agricultural and Animal Husbandry Sciences Lhasa 850009 ChinaCollege of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaCollege of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaCollege of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaCollege of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaNovus International Inc Research Park Drive Saint Charles MO 63304 USACollege of Animal Science and Technology Gansu Agricultural University Lanzhou 730070 ChinaInstitute of Animal Nutrition and Dietetics Vetsuisse‐Faculty University of Zurich Zurich 8057 SwitzerlandCollege of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaCollege of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaCollege of Animal Science and Technology Northwest A&F University Yangling 712100 ChinaAbstract Carvacrol and thymol (CAT) have been widely recognized for their antimicrobial and anti‐inflammatory properties, yet their specific effects on colitis and the mechanisms involved remain insufficiently understood. This study establishes a causative link between CAT administration and colitis mitigation, primarily through the enhancement of Bifidobacterium pseudolongum abundance in the colon. This increase promotes the production of secondary bile acids, particularly hyodeoxycholic acid (HDCA) and 12‐ketodeoxycholic acid (12‐KCAC), which exert anti‐inflammatory effects. Notably, CAT does not alleviate colitis symptoms in germ‐free mice, indicating the necessity of gut microbiota. This research uncovers a novel regulatory mechanism where HDCA and 12‐KCAC inhibit colonic inflammation by reducing the expression of transmembrane guanylate cyclase 1A in the colonic epithelium. This downregulation elevates intracellular Ca2+ and cGMP levels, activating protein kinase G (PKG). Activated PKG subsequently suppresses the mTOR signaling pathway, thereby ameliorating dextran sulfate sodium (DSS)‐induced colonic damage. These findings highlight potential metabolites and therapeutic targets for preventing and treating colitis. Bifidobacterium pseudolongum, HDCA, and 12‐KCAC emerge as promising candidates for therapeutic interventions in colitis and related disorders characterized by impaired tight junction function.https://doi.org/10.1002/advs.20240691712‐ketodeoxycholic acidbile acidgut microbiotainflammatory bowel diseasemTOR |
| spellingShingle | Ke Zhang Yangbin Xu Yining Zheng Ting Zhang Yujiang Wu Yiting Yan Yu Lei Xi Cao Xiaolong Wang Frances Yan Zhaomin Lei Daniel Brugger Yulin Chen Lu Deng Yuxin Yang Bifidobacterium pseudolongum‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 Pathway Advanced Science 12‐ketodeoxycholic acid bile acid gut microbiota inflammatory bowel disease mTOR |
| title | Bifidobacterium pseudolongum‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 Pathway |
| title_full | Bifidobacterium pseudolongum‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 Pathway |
| title_fullStr | Bifidobacterium pseudolongum‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 Pathway |
| title_full_unstemmed | Bifidobacterium pseudolongum‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 Pathway |
| title_short | Bifidobacterium pseudolongum‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 Pathway |
| title_sort | bifidobacterium pseudolongum derived bile acid from dietary carvacrol and thymol supplementation attenuates colitis via cgmp pkg mtorc1 pathway |
| topic | 12‐ketodeoxycholic acid bile acid gut microbiota inflammatory bowel disease mTOR |
| url | https://doi.org/10.1002/advs.202406917 |
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