Gpr35 shapes gut microbial ecology to modulate hepatic steatosis
The gut microbiome is closely shaped by host genetic and dietary factors to regulate metabolic health and disease. However, the signaling mechanisms underlying such interactions have been largely unclear. Here we identify G protein-coupled receptor 35 (Gpr35) as a regulator of gut microbial ecology...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661823000464 |
| _version_ | 1797448111042330624 |
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| author | Xin Wu Shuobing Chen Qingyuan Yan Feng Yu Hua Shao Xiao Zheng Xueli Zhang |
| author_facet | Xin Wu Shuobing Chen Qingyuan Yan Feng Yu Hua Shao Xiao Zheng Xueli Zhang |
| author_sort | Xin Wu |
| collection | DOAJ |
| description | The gut microbiome is closely shaped by host genetic and dietary factors to regulate metabolic health and disease. However, the signaling mechanisms underlying such interactions have been largely unclear. Here we identify G protein-coupled receptor 35 (Gpr35) as a regulator of gut microbial ecology and the susceptibility to obesity and hepatic steatosis in mice. Both global and intestinal epithelia specific ablation of Gpr35 aggravated high-fat diet (HFD)-induced metabolic disturbance and hepatic steatosis in mice. Gpr35 deficiency induced a remarkable loss of goblet cells and an extensive remodeling of the gut microbiome, featuring enrichment of the Bacteroides and Ruminococcus genera. Antibiotics treatment and co-housing alleviated the metabolic disturbance markers in Gpr35 deficient mice. Spatiotemporal profiling and mono-colonization screening revealed that Ruminococcus gnavus synergized with HFD to promote hepatic steatosis possibly via tryptophan and phenylalanine pathway metabolites. Our results provide mechanistic insights into a genetic-diet-microbe interplay that dictates susceptibility to metabolic disorder. |
| first_indexed | 2024-03-09T14:05:43Z |
| format | Article |
| id | doaj.art-4515d3718d4e450f8ff0fdfeabfd94c2 |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-09T14:05:43Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-4515d3718d4e450f8ff0fdfeabfd94c22023-11-30T05:05:45ZengElsevierPharmacological Research1096-11862023-03-01189106690Gpr35 shapes gut microbial ecology to modulate hepatic steatosisXin Wu0Shuobing Chen1Qingyuan Yan2Feng Yu3Hua Shao4Xiao Zheng5Xueli Zhang6Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu, ChinaDepartment of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu, ChinaState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu, China; Laboratory of Metabolic Regulation and Drug Target Discovery, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, Jiangsu, ChinaSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, ChinaDepartment of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China; Corresponding authors.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu, China; Laboratory of Metabolic Regulation and Drug Target Discovery, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, Jiangsu, China; Corresponding author at: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China; Corresponding authors.The gut microbiome is closely shaped by host genetic and dietary factors to regulate metabolic health and disease. However, the signaling mechanisms underlying such interactions have been largely unclear. Here we identify G protein-coupled receptor 35 (Gpr35) as a regulator of gut microbial ecology and the susceptibility to obesity and hepatic steatosis in mice. Both global and intestinal epithelia specific ablation of Gpr35 aggravated high-fat diet (HFD)-induced metabolic disturbance and hepatic steatosis in mice. Gpr35 deficiency induced a remarkable loss of goblet cells and an extensive remodeling of the gut microbiome, featuring enrichment of the Bacteroides and Ruminococcus genera. Antibiotics treatment and co-housing alleviated the metabolic disturbance markers in Gpr35 deficient mice. Spatiotemporal profiling and mono-colonization screening revealed that Ruminococcus gnavus synergized with HFD to promote hepatic steatosis possibly via tryptophan and phenylalanine pathway metabolites. Our results provide mechanistic insights into a genetic-diet-microbe interplay that dictates susceptibility to metabolic disorder.http://www.sciencedirect.com/science/article/pii/S1043661823000464Gpr35Gut dysbiosisGoblet cellsRuminococcus gnavusGut-liver axisLiver steatosis |
| spellingShingle | Xin Wu Shuobing Chen Qingyuan Yan Feng Yu Hua Shao Xiao Zheng Xueli Zhang Gpr35 shapes gut microbial ecology to modulate hepatic steatosis Pharmacological Research Gpr35 Gut dysbiosis Goblet cells Ruminococcus gnavus Gut-liver axis Liver steatosis |
| title | Gpr35 shapes gut microbial ecology to modulate hepatic steatosis |
| title_full | Gpr35 shapes gut microbial ecology to modulate hepatic steatosis |
| title_fullStr | Gpr35 shapes gut microbial ecology to modulate hepatic steatosis |
| title_full_unstemmed | Gpr35 shapes gut microbial ecology to modulate hepatic steatosis |
| title_short | Gpr35 shapes gut microbial ecology to modulate hepatic steatosis |
| title_sort | gpr35 shapes gut microbial ecology to modulate hepatic steatosis |
| topic | Gpr35 Gut dysbiosis Goblet cells Ruminococcus gnavus Gut-liver axis Liver steatosis |
| url | http://www.sciencedirect.com/science/article/pii/S1043661823000464 |
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