GUT MICROBIOTA AS A MODULATOR OF ENDOCRINE GLAND FUNCTION: A REVIEW OF THE GUT-ENDOCRINE AXIS BEYOND THE GUT-BRAIN CONNECTION.

Abstract

The gut microbiota, the dynamic community of bacteria, viruses, fungi, and archaea present in the gastrointestinal tract, has been studied under the perspective of the gut-brain axis. Recent studies, however, report that microbial interactions with host physiology are much more than neurological—microbial modulation of endocrine gland function is now well established. A summary of recent knowledge of the gut-endocrine axis, focusing on the role of metabolites of the gut microbiome, such as short-chain fatty acids, secondary bile acids, indole derivatives and lipopolysaccharide, in communicating to distant organs and immune pathways by vagal and humoral pathways. We discuss microbiota regulation of endocrine system tone and dynamics, including the hypothalamic-pituitary-adrenal axis, thyroid hormone synthesis, thyroid autoimmunity, pancreatic beta-cell function, sex steroid metabolism (estrobolome and testobolome), adipokine regulation, energy storage in fat, calcium-vitamin D homeostasis, and gut-derived melatonin production, with implications for PCOS and for fertility and growth hormone-IGF-1 axis dynamics. We also review the microbiome and metabolite related diagnostic biomarkers, sex- and age-dependent variations in gut-endocrine relationships, and evidence supporting probiotic, prebiotic, synbiotic, and fecal microbiota transplantations interventions. Although there is strong mechanistic evidence supporting the gut microbiota as an active endocrine regulator, as yet there are only small clinical trials available, with variable effects and with diet and medication as confounding factors. In conclusion, the gut-endocrine axis is a biologically coherent system that is not widely studied in clinical trials of humans, particularly one that needs to be sex-and age-stratified, and it is a system that is clearly interconnected and has therapeutic potential.