Deletion of hepatic growth hormone receptor (GHR) alters the mouse gut microbiota by affecting bile acid metabolism
Zichao Yu,
Yu Wang,
Fang Zhang,
Rui Ma,
Xiaoyu Yang,
Kun Yang,
Ai Mi,
Liyuan Ran,
Yingjie Wu
Affiliations
Zichao Yu
Shandong Provincial Hospital Affiliated to Shandong First Medical University & Shandong Academy of Medical Sciences, School of Laboratory Animal & Shandong Laboratory Animal Center, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
Yu Wang
Shandong Provincial Hospital Affiliated to Shandong First Medical University & Shandong Academy of Medical Sciences, School of Laboratory Animal & Shandong Laboratory Animal Center, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
Fang Zhang
Shandong Provincial Hospital Affiliated to Shandong First Medical University & Shandong Academy of Medical Sciences, School of Laboratory Animal & Shandong Laboratory Animal Center, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
Rui Ma
Institute of Genome Engineered Animal Models for Human Diseases, Dalian Medical University, Dalian, China
Xiaoyu Yang
Shandong Provincial Hospital Affiliated to Shandong First Medical University & Shandong Academy of Medical Sciences, School of Laboratory Animal & Shandong Laboratory Animal Center, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
Kun Yang
Shandong Provincial Hospital Affiliated to Shandong First Medical University & Shandong Academy of Medical Sciences, School of Laboratory Animal & Shandong Laboratory Animal Center, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
Ai Mi
Institute of Genome Engineered Animal Models for Human Diseases, Dalian Medical University, Dalian, China
Liyuan Ran
Shandong Provincial Hospital Affiliated to Shandong First Medical University & Shandong Academy of Medical Sciences, School of Laboratory Animal & Shandong Laboratory Animal Center, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
Yingjie Wu
Shandong Provincial Hospital Affiliated to Shandong First Medical University & Shandong Academy of Medical Sciences, School of Laboratory Animal & Shandong Laboratory Animal Center, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
ABSTRACTBoth growth hormone (GH) and gut microbiota play significant roles in diverse physiological processes, but the crosstalk between them is poorly understood. Despite the regulation of GH by gut microbiota, study on GH’s influence on gut microbiota is limited, especially on the impacts of tissue specific GH signaling and their feedback effects on the host. In this study, we profiled gut microbiota and metabolome in tissue-specific GHR knockout mice in the liver (LKO) and adipose tissue (AKO). We found that GHR disruption in the liver rather than adipose tissue affected gut microbiota. It changed the abundance of Bacteroidota and Firmicutes at phylum level as well as abundance of several genera, such as Lactobacillus, Muribaculaceae, and Parasutterella, without affecting α-diversity. Moreover, the impaired liver bile acid (BA) profile in LKO mice was strongly associated with the change of gut microbiota. The BA pools and 12-OH BAs/non-12-OH BAs ratio were increased in the LKO mice, which was due to the induction of CYP8B1 by hepatic Ghr knockout. Consequently, the impaired BA pool in cecal content interacted with gut bacteria, which in turn increased the production of bacteria derived acetic acid, propionic acid, and phenylacetic acid that were possible to participate in the impaired metabolic phenotype of the LKO mice. Collectively, our findings suggested that the liver GH signaling regulates BA metabolism by its direct regulation on CYP8B1, which is an important factor influencing gut microbiota. Our study is significant in exploring gut microbiota modification effects of tissue-specific GH signaling as well as its involvement in gut microbiota–host interaction.
