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

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 effect of excess GH action on the longitudinal changes in the gut microbial profile (ie, abundance, diversity/maturity, predictive metabolic function, and short-chain fatty acid [SCFA] levels) of bovine GH (bGH) transgenic mice at age 3, 6, and 12 months 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 (ie, 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 3 time points, 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.

Growth hormone alters gross anatomy and morphology of the small and large intestines in age- and sex-dependent manners.

PURPOSE: Growth hormone (GH) has an important role in intestinal barrier function, and abnormalities in GH action have been associated with intestinal complications. Yet, the impact of altered GH on intestinal gross anatomy and morphology remains unclear. METHODS: This study investigated the influence of GH signaling on gross anatomy, morphology, and fibrosis by characterizing the small and large intestines in male and female bovine growth hormone transgenic (bGH) mice and GH receptor gene-disrupted (GHR-/-) mice at multiple timepoints. RESULTS: The length, weight, and circumference of the small and large intestines were increased in bGH mice and decreased in GHR-/- mice across all ages. Colon circumference was significantly increased in bGH mice in a sex-dependent manner while significantly decreased in male GHR-/- mice. Villus height, crypt depth, and muscle thickness of the small intestine were generally increased in bGH mice and decreased in GHR-/- mice compared to controls with age- and sex-dependent exceptions. Colonic crypt depth and muscle thickness in bGH and GHR-/- mice were significantly altered in an age- and sex-dependent manner. Fibrosis was increased in the small intestine of bGH males at 4 months of age, but no significant differences were seen between genotypes at other timepoints. CONCLUSION: This study observed notable opposing findings in the intestinal phenotype between mouse lines with GH action positively associated with intestinal gross anatomy (i.e. length, weight, and circumference). Moreover, GH action appears to alter morphology of the small and large intestines in an age- and sex-dependent manner.

Crosstalk between the growth hormone/insulin-like growth factor-1 axis and the gut microbiome: A new frontier for microbial endocrinology.

Both the GH/IGF-1 axis and the gut microbiota independently play an important role in host growth, metabolism, and intestinal homeostasis. Inversely, abnormalities in GH action and microbial dysbiosis (or a lack of diversity) in the gut have been implicated in restricted growth, metabolic disorders (such as chronic undernutrition, anorexia nervosa, obesity, and diabetes), and intestinal dysfunction (such as pediatric Crohn's disease, colonic polyps, and colon cancer). Over the last decade, studies have demonstrated that the microbial impact on growth may be mediated through the GH/IGF-1 axis, pointing toward a potential relationship between GH and the gut microbiota. This review covers current research on the GH/IGF-1 axis and the gut microbiome and its influence on overall host growth, metabolism, and intestinal health, proposing a bidirectional relationship between GH and the gut microbiome.