Excess Growth Hormone Alters the Male Mouse Gut Microbiome in an Age-dependent Manner

Abstract

The gut microbiome has an important role in host development, metabolism, growth, and aging. Recent research points toward potential crosstalk between the gut microbiota and the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. Our laboratory previously showed that GH excess and deficiency are associated with an altered gut microbial composition in adult mice. Yet, no study to date has examined the influence of GH on the gut microbiome over time. Our study thus tracked the impact of excess GH action on the longitudinal changes in the gut microbial profile (i.e. abundance, diversity/maturity, predictive metabolic function, and short chain fatty acid [SCFAs] levels) of bovine GH (bGH) transgenic mice at 3, 6, and 12 months of age compared to littermate controls in the context of metabolism, intestinal phenotype, and premature aging. The bGH mice displayed age-dependent changes in microbial abundance, richness, and evenness. Microbial maturity was significantly explained by genotype and age. Moreover, several bacteria (i.e. Lactobacillus, Lachnospiraceae, Bifidobacterium, and Faecalibaculum), predictive metabolic pathways (such as SCFA, vitamin B12, folate, menaquinol, peptidoglycan, and heme B biosynthesis), and SCFA levels (acetate, butyrate, lactate, and propionate) were consistently altered across all three timepoints, differentiating the longitudinal bGH microbiome from controls. Of note, the bGH mice also had significantly impaired intestinal fat absorption with increased fecal output. Collectively, these findings suggest that excess GH alters the gut microbiome in an age-dependent manner with distinct longitudinal microbial and predicted metabolic pathway signatures.

Deletion of hepatic growth hormone receptor (GHR) alters the mouse gut microbiota by affecting bile acid metabolism

“…The abundances of Firmicutes and Bacteroidota dominated in murine gut microbiome as well as many genera belonging to them were significantly changed in the LKO mice. Interestingly, they were not changed in the global GH overexpress or GH gene knockout mice, 19 , 20 which suggested the compensatory effect of GH action in different organs. Moreover, Parasutterella significantly reduced in the LKO mice showed the same and opposite trends with that in GH −/− and GH transgenic mice, 19 respectively.…”

“…demonstrated that global GH excess and deficiency affected the gut microbiota in mature adult and middle-aged mice. 19 , 20 Moreover, the gut microbiota in patients with GH-secreting pituitary adenoma is significantly altered and strongly associated with GH/IGF-1 axis. 21 Therefore, exploring the roles of GH signaling in gut microbiota regulation can provide a better understanding of the pathophysiological process of diseases related to impaired GH axis.…”

Association between gut microbiota and erectile dysfunction: a two-sample Mendelian randomization study

“…SCFA, as the major end product of human intestinal ora metabolism is the main source of nutrients for intestinal epithelial cells (IEC) (40). It can regulate IEC function through different mechanisms by affecting their proliferation, differentiation, and regulate enteroendocrine cells functions of hormones secretion (41), including sex hormones (42,43), also it have an impact on host cardiovascular and lipid metabolism (40,(44)(45)(46). Meanwhile, because of Gut-Brain axis, SCFAs can activate G protein coupled receptors , penetrate the blood-brain barrier (47) and have function on the regulation of central nervous system(48,49).Moreover, SCFA can promote the growth of human neural stem cell as well as the differentiation of embryonic stem cells into neural cells, and promote the proliferation of human neural progenitor cells (50,51).…”

Growth Hormone Alters Circulating Levels of Glycine and Hydroxyproline in Mice

“…Fecal Sample Collection—bGH and GHRKO mice were fasted for 6 h, and fecal samples were collected as described previously [ 16 , 17 ]. Briefly, mice were allowed to defecate naturally on a sterilized surface or encouraged to defecate through gentle massage in the hind-back region.…”