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

Abstract

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.

Early-life adversity and brain development: Is the microbiome a missing piece of the puzzle?

“…In addition to a lower prevalence of Bifidobacteria, the microbiota of formula-fed infants appears to have an increased diversity and a high abundance of coliforms, Bacteroides and Clostridium difficile (Yoshioka et al, 1983, Harmsen et al, 2000, Penders et al, 2006, Saavedra, 2007, Azad et al, 2013. One metabolic consequence of these differences is a microbiota with enhanced folate producing capability in breastfed infants versus increased butyrate production in the more complex preteolytic oriented microbiota of formula fed infants (Mischke and Plosch, 2013).…”

Microbiome Disturbances and Autism Spectrum Disorders

“…The field of neuroepigenetics was born under these auspices and is currently invoked as the genesis of many neurologic disorders not explained by genetics alone, including ASD (Wilkinson and Campbell, 2013;Berko et al, 2014;Ladd-Acosta et al, 2014;Lesseur et al, 2014;Tordjman et al, 2014;Wong et al, 2014). Alterations in the gut microbiome might trigger epigenetic changes leading to downstream behavioral manifestations (Mischke and Plösch, 2013;Kumar et al, 2014;Stilling et al, 2014).…”

High or low dietary carbohydrate:protein ratios during first-feeding affect glucose metabolism and intestinal microbiota in juvenile rainbow trout

“…The strong increase in carbohydrates was adjusted for by a concomitant decrease in dietary protein. Thus, the main objective of the present work was to assess the short-and long-term effects of first-feeding rainbow trout alevins with a high level of carbohydrates and a low level of protein on metabolic programming with respect to: (1) the regulation of genes involved in glucose and amino acid digestion, transport and/or metabolism, (2) the expression of specific microRNAs involved in metabolism and (3) the composition of the gut microbiota, whose composition and metabolites are influenced by the diet, with potential epigenetic consequences (Mischke and Plösch, 2013). In order to assess the long-term effect of the early stimulus, we performed a challenge test during which juvenile rainbow trout were fed a diet marginally adequate in protein [36%, the recommended dietary protein for rainbow trout being 38% of diet (NRC, 2011)] but rich in carbohydrates (28%).…”