Neonatal Programming of Microbiota Composition: A Plausible Idea That Is Not Supported by the Evidence

Abstract

Underpinning the theory "developmental origins of health and disease" (DOHaD), evidence is accumulating to suggest that the risks of adult disease are in part programmed by exposure to environmental factors during the highly plastic "first 1,000 days of life" period. An elucidation of the mechanisms involved in this programming is challenging as it would help developing new strategies to promote adult health. The intestinal microbiome is proposed as a long-lasting memory of the neonatal environment. This proposal is supported by indisputable findings such as the concomitance of microbiota assembly and the first 1,000-day period, the influence of perinatal conditions on microbiota composition, and the impact of microbiota composition on host physiology, and is based on the widely held but unconfirmed view that the microbiota is long-lastingly shaped early in life. In this review, we examine the plausibility of the gut microbiota being programmed by the neonatal environment and evaluate the evidence for its validity. We highlight that the capacity of the pioneer bacteria to control the implantation of subsequent bacteria is supported by both theoretical principles and statistical associations, but remains to be demonstrated experimentally. In addition, our critical review of the literature on the long-term repercussions of selected neonatal modulations of the gut microbiota indicates that sustained programming of the microbiota composition by neonatal events is unlikely. This does not exclude the microbiota having a role in DOHaD due to a possible interaction with tissue and organ development during the critical windows of neonatal life.

Keywords: DOHaD; first thousand days of life; neonatal gut microbiome; perinatality; programming.

FIGURE 1

Illustration for the disappearance of the impact of neonatal prebiotic supplementations on caecal bacterial communities in rats: pups supplemented with different prebiotics [alpha Galacto-oligosaccharide, Fructo-oligosaccharides or a mix (9:1) of beta-Galacto-oligosaccharides and inulin] from post natal day 5–14/15 clustered together but did not overlap with pups from the CTL group at the end of the supplementation (PND14/15): they exhibited a clearly distinct microbial community as compared to unsupplemented pups. This was no longer true in adulthood (PND124/126) where all individuals clustered together [multidimensional scaling (MDS) analysis based on dissimilarities measures (Bray–Curtis) calculated from data published by Le Dréan et al., 2019].