Growth hormone deficiency and excess alter the gut microbiome in adult male mice

The gut microbiome has been implicated in host metabolism, endocrinology, and pathophysiology. Furthermore, several studies have shown that gut bacteria impact host growth, partially mediated through the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. Yet, no study to date has examined the specific role of GH on the gut microbiome. Our study thus characterized the adult gut microbial profile and intestinal phenotype in GH gene-disrupted (GH-/-) mice (a model of GH deficiency) and bovine GH transgenic (bGH) mice (a model of chronic, excess GH action) at six months of age. Both the GH-/- and bGH mice had altered microbial signatures, which were in opposing directions at the phylum and genus levels. For example, GH-/- mice had significantly reduced abundance in Proteobacteria, Campylobacterota, and Actinobacteria phyla, whereas bGH mice exhibited a trending increase in those phyla compared to respective controls. Analysis of maturity of the microbial community demonstrated that lack of GH resulted in a significantly more immature microbiome while excess GH increases microbial maturity. Several common bacterial genera were shared, although in opposing directions, between the two mouse lines (e.g. decreased in GH-/- mice and increased in bGH mice), suggesting an association with GH. Likewise, metabolic pathways like acetate, butyrate, heme B and folate biosynthesis were predicted to be impacted by GH. This study is the first to characterize the gut microbiome in mouse lines with altered GH action and indicates that GH may play a role in the growth of certain microbiota thus impacting microbial maturation and metabolic function.