More than just a gut instinct-the potential interplay between a baby's nutrition, its gut microbiome, and the epigenome

Am J Physiol Regul Integr Comp Physiol. 2013 Jun 15;304(12):R1065-9. doi: 10.1152/ajpregu.00551.2012. Epub 2013 Apr 17.


Substantial evidence links early postnatal nutrition to the development of obesity later in life. However, the molecular mechanisms of this connection must be further elucidated. Epigenetic mechanisms have been indicated to be involved in this process, referred to as metabolic programming. Therefore, we propose here that early postnatal nutrition (breast and formula feeding) epigenetically programs the developing organs via modulation of the gut microbiome and influences the body weight phenotype including the predisposition to obesity. Specifically, the early-age food patterns are known to determine the gross composition of the early gut microbiota. In turn, the microbiota produces large quantities of epigenetically active metabolites, such as folate and short chain fatty acids (butyrate and acetate). The spectrum of these produced metabolites depends on the composition of the gut microbiota. Hence, it is likely that changes in gut microbiota that result in altered metabolite composition might influence the epigenome of directly adjacent intestinal cells, as well as other major target cell populations, such as hepatocytes and adipocytes. Nuclear receptors and other transcription factors (the PPARs, LXR, RXR, and others) could be physiologically relevant targets of this metabolite-induced epigenetic regulation. Ultimately, transcriptional networks regulating energy balance could be manipulated. For these reasons, we postulate that early nutrition may influence the baby epigenome via microbial metabolites, which contributes to the observed relationship between early nutrition and adult obesity.

Keywords: baby nutrition; bacterial metabolites; epigenetic programming; gut flora; microbiome.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Epigenesis, Genetic / physiology*
  • Fetal Development / physiology
  • Gastrointestinal Tract / microbiology*
  • Gastrointestinal Tract / physiology
  • Humans
  • Infant Nutritional Physiological Phenomena / physiology*
  • Infant, Newborn
  • Metagenome / physiology*
  • Mice
  • Obesity / physiopathology
  • Phenotype