MON-473 Growth Hormone (GH) Impacts the Gut Microbial Profile: the Presence of Unique Bacterial Genera in Mouse Lines with Altered GH Action

Abstract

Several recent studies have shown that gut microbiota can regulate the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, or specifically modulate endocrine IGF-1. Yet, the impact of GH on the gut microbiome has not been evaluated. This study characterized the fecal microbial profile in GH gene disrupted (GH-/-) mice and bovine GH transgenic (bGH) mice at 6 months of age compared to their respective littermate controls. Microbial abundance and diversity were quantified from fecal pellets of these four groups through 16S rRNA sequencing. Additional bioinformatics analyses assessed the unique microbial signature and predictive biological function of the microbiome. Both GH-/- and bGH mice exhibited a unique microbial profile. In terms of microbial abundance, GH-/- and bGH mice resulted in a similar significant shift in the ratio of Firmicutes to Bacteroidetes. However, GH-/- and bGH mice differed in abundance of the Proteobacteria and Epsilonbacteraeota phyla with a significant reduction in abundance in GH-/- mice and significantly increased abundance in bGH mice. The GH-/- microbiome exhibited a distinct microbial signature with microbial immaturity and a predictive biological function associated with increased carbohydrate metabolism and decreased antimicrobial synthesis. The bGH microbiome also had a unique microbial signature with increased microbial richness and evenness. Moreover, both mouse lines shared common bacterial candidates. Common bacterial genera like Turicibacter, Ruminococcaceae and Faecalibaculum had similar abundance profiles in the bGH mice and GH-/- mice (i.e. either upregulated or downregulated with both increased and decreased GH action). Interestingly, however, other bacteria, such as Parasutterella, Lachnospiraceae and Rikenellaceae, followed opposite trends between bGH and GH-/- mice (i.e. upregulated with increased GH action and downregulated with decreased GH action). Collectively, these results demonstrate that GH - in both states of excess and deficiency - yields a distinct microbial profile, including microbial abundance, diversity and potential function. More importantly, the common bacterial candidates like Parasutterella suggest that GH action influences the presence of certain gut microbiota. Additional studies will be conducted to further explore these unique GH-associated bacterial candidates and their impact on metabolic and intestinal health of the host. This work was partially funded by the John J. Kopchick Molecular and Cellular Biology/Translational Biomedical Sciences Research Fellowship, the Osteopathic Heritage Foundation, Dual Degree Program at Ohio University Heritage College of Osteopathic Medicine and the Mouse Metabolic Phenotyping Center at University of California, Davis (NIH grant U240DK092993).