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.

The contribution of maternal oral, vaginal, and gut microbiota to the developing offspring gut

“…3 ). This increase in similarity is expected, and has repeatedly been reported in the literature of both human and mouse model as a hallmark of GM 17 , 38 . The contribution of maternal microbial sites to the neonatal GM varies between different SPF GMs.…”

The contribution of maternal oral, vaginal, and gut microbiota to the developing offspring gut

“…As pups age, both fecal and ileal GM beta diversity became increasingly similar to maternal fecal and ileal samples respectively, as well as inter-individual similarity within pups (Figure 3 and Supplemental Figure 3). This increase in similarity is expected, and has repeatedly been reported in the literature of both human and mouse model as a hallmark of GM 14,32 . The contribution of maternal microbial sites to the neonatal gut microbiota varies between different SPF GMs.…”

Comparative analysis of pectin and prebiotics on human microbiota modulation in early life stages and adults

“…35 However, research suggests that these initial differences in gut microbiota composition may disappear after the first year when the microbiota starts to mature. 37 Beyond the mode of delivery, early antibiotic use and feeding practices can affect the neonate's microbiota. Previous research demonstrates that antibiotic use in newborns reduces overall microbiota diversity.…”

“…35 However, research suggests that these initial differences in gut microbiota composition may disappear after the first year when the microbiota starts to mature. 37…”