ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Endocrinology, April 2020, 161(4):1–18

The aim of this study was to examine the role of growth hormone (GH) on gut microbiome and intestinal phenotype by using two animal models characterized by an opposite GH status: GH gene-disrupted (GH-/-) mice, characterized by GH deficiency; and bovine GH transgenic (bGH) mice with chronic GH excess. The abundance of common bacterial genera, such as Parasutterella, Ruminococcaceae NK4A214, Rikenellaceae, and Lactobacillus, differed between the GH deficient and GH excess mouse lines. Similarly, metabolic pathways that are regulated in opposite directions between the 2 mouse lines were identified. Finally, opposing intestinal gross anatomy, histology, and fecal output between the 2 mouse lines were found. Taken together, these findings suggest an impact of GH on gut microbial profile (abundance and maturity), metabolic pathways regulated by microbial community (acetate, butyrate, heme B, and folate biosynthesis) and intestinal phenotype (gross anatomy, histology, inflammation and fecal output).

The gut microbiome is a complex ecosystem, complementary and tightly interconnected with human host for the regulation of functions, such as the fermentation of indigestible dietary components, the synthesis of important elements, the removal of toxic compounds, the out competition of pathogens, the strengthening of the intestinal barrier, and the stimulation and regulation of the immune system (1). A healthy person typically hosts trillions of microbes, which differ between individuals, being the taxonomic composition of the gut microbiome influenced by factors including lifestyle and drugs (2). Recent studies have suggested a relationship between the gut microbiota and GH/IGF-1 axis. Gut microbiota exerts an anabolic effect on bone, likely mediated by the dynamic regulation of IGF-I levels (3). An altered microbiota composition has been detected in Ames dwarf mice, which have multiple hormonal deficiencies including GH, prolactin, and thyrotropin due to a mutation of the Prop1 gene (4).

This study shows, for the first time, a close relationship of GH status with gut microbiota and the metabolic pathways regulated by microbiota. Further studies are warranted to clarify the mechanisms underlying this relationship.

References:

1. Sommer F, Bäckhed F. The gut microbiota--masters of host development and physiology. Nat Rev Microbiol. 2013;11(4):227–38.

2. Schmidt TSB, Raes J, Bork P. The Human Gut Microbiome: From Association to Modulation. Cell. 2018;172(6):1198–215.

3. Yan J, Herzog JW, Tsang K, Brennan CA, Bower MA, Garrett WS, et al. Gut microbiota induce IGF-1 and promote bone formation and growth. Proc Natl Acad Sci U S A. 2016;113(47):E7554–e63.

4. Wiesenborn DS, Gálvez EJC, Spinel L, Victoria B, Allen B, Schneider A, et al. The role of Ames dwarfism and calorie restriction on gut microbiota. J Gerontol A Biol Sci Med Sci. 2019.