Minireview: Gut microbiota: the neglected endocrine organ

Mol Endocrinol. 2014 Aug;28(8):1221-38. doi: 10.1210/me.2014-1108. Epub 2014 Jun 3.

Abstract

The concept that the gut microbiota serves as a virtual endocrine organ arises from a number of important observations. Evidence for a direct role arises from its metabolic capacity to produce and regulate multiple compounds that reach the circulation and act to influence the function of distal organs and systems. For example, metabolism of carbohydrates results in the production of short-chain fatty acids, such as butyrate and propionate, which provide an important source of nutrients as well as regulatory control of the host digestive system. This influence over host metabolism is also seen in the ability of the prebiotic inulin to influence production of relevant hormones such as glucagon-like peptide-1, peptide YY, ghrelin, and leptin. Moreover, the probiotic Lactobacillus rhamnosus PL60, which produces conjugated linoleic acid, has been shown to reduce body-weight gain and white adipose tissue without effects on food intake. Manipulating the microbial composition of the gastrointestinal tract modulates plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Indirectly and through as yet unknown mechanisms, the gut microbiota exerts control over the hypothalamic-pituitary-adrenal axis. This is clear from studies on animals raised in a germ-free environment, who show exaggerated responses to psychological stress, which normalizes after monocolonization by certain bacterial species including Bifidobacterium infantis. It is tempting to speculate that therapeutic targeting of the gut microbiota may be useful in treating stress-related disorders and metabolic diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gastrointestinal Tract / microbiology*
  • Gastrointestinal Tract / physiology
  • Hormones / physiology*
  • Humans
  • Hypothalamo-Hypophyseal System
  • Microbiota / physiology*
  • Pituitary-Adrenal System
  • Tryptophan / metabolism

Substances

  • Hormones
  • Tryptophan

Grants and funding

The Alimentary Pharmabiotic Centre is a research center funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan. The authors and their work were supported by SFI (Grants SFI/12/RC/2273, 02/CE/B124, and 07/CE/B1368) and by the Health Research Board (HRB) through Health Research Awards (Grant HRA_POR/2011/23 to T.G.D., J.F.C., and G.C.). The Centre has conducted studies in collaboration with several companies including GSK, Pfizer, Wyeth, and Mead Johnson. J.F.C. is also funded by the European Community's Seventh Framework Programme (Grant FP7/2007–2013, Grant Agreement 201 714). G.C. is supported by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (Grant 20771).