Maternal and Breast Milk Influences on the Infant Gut Microbiome, Enteric Health and Growth Outcomes of Rhesus Monkeys

Abstract

Objectives: Gut bacteria play an essential role during infancy and are strongly influenced by the mode of birth and feeding. A primate model was used to investigate the benefits of exposure to the mother or conversely the negative impact of early nursery rearing on microbial colonization. Method: Rectal swabs were obtained from rhesus macaques born vaginally and mother-reared (MR, N = 35) or delivered primarily via cesarean-section and human-reared (HR, N = 19). Microbiome composition was determined by rRNA gene amplicon sequencing at 2, 4, and 8 weeks of age and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs used to assess influences on functional metabolic pathways in the gut. Growth trajectories and incidence of diarrheic symptoms were evaluated. Results: The microbial community structure was different between MR and HR infants with respect to phylogeny and abundance at all 3 ages. When examining dominant phyla, HR infants had a higher Firmicutes-to-Bacteroidetes ratio. At the genus level, breast milk-dependent commensal taxa and adult-typical genera were more abundant in MR infants. This difference resulted in a corresponding shift in the predicted metabolic effects, specifically for microbial genes associated with metabolism and immune function. HR infants had faster growth trajectories (P < 0.001), but more diarrheic symptoms by 6 months postnatal (P = 0.008). Conclusions: MR infants acquired adult-typical microbiota more quickly, and had higher levels of several beneficial commensal taxa. Cesarean-delivered and formula-fed infants had different developmental trajectories of bacterial colonization. Establishment of the gut microbiome was associated with an infant's growth trajectory, and implicated in the subsequent vulnerability to Campylobacter infections associated with diarrhea in infant monkeys.

Proteobacteria abundance during nursing predicts physical growth and brain volume at one year of age in young rhesus monkeys

“…Infant microbial profiles were dominated by Firmicutes at all time points, accounting for 52.6% of the total reads, followed by Bacteroidetes (31.9%), Proteobacteria (7.2%), and Actinobacteria (5.8%) (Figure 2A). In accordance with previous primate studies, 52,53 the predominant genus isolated from swabs was Prevotella within Bacteroidetes, which shifted significantly over the first year of life (LME: P = .003; Figure 2B). It increased 11% from abundances at 2 weeks of infant age as infants transitioned to solid foods before stabilizing.…”

“…The progressive shifts in the bacterial taxa that occur in the infant monkey are generally consistent with the human literature 1,55 . However, we and a number of other research groups have shown previously that the microbial composition of the infant monkey gut can be strongly influenced by breast milk and is markedly different if fed formula by humans in a nursery setting 6,57,58 . The initial nursing phase is characterized by less microbial diversity due to the predominance of taxa within Actinobacteria and Proteobacteria.…”

“…1,55 However, we and a number of other research groups have shown previously that the microbial composition of the infant monkey gut can be strongly influenced by breast milk and is markedly different if fed formula by humans in a nursery setting. 6,57,58 The initial nursing phase is characterized by less microbial diversity due to the predominance of taxa within Actinobacteria and Proteobacteria. The commensal genus Bifidobacterium then plays a key role in the metabolism of breast milk oligosaccharides and was found, as hypothesized, to be most abundant during the peak months of nursing.…”

Neonatal Immune System Ontogeny: The Role of Maternal Microbiota and Associated Factors. How Might the Non-Human Primate Model Enlighten the Path?

“…However, we do know from animal studies if the mode of delivery can impact host immunity directly [108]. The NHP model could be useful to address the impact of the mode of delivery on the development of the immune system in longitudinal studies taking into account the temporal dynamics of vaginal microbiota and other confounding factors [109].…”

A Healthy Gut for a Healthy Brain: Preclinical, Clinical and Regulatory Aspects

“…Breast-fed and formula-fed infants present a different relative abundance of some phyla of bacteria [ 34 ]. The microbiota of breast-fed babies is more heterogeneous than that of formula-fed babies and contains a higher taxonomic diversity [ 35 ]. Mammary microbiota derives from the entero-mammary pathway through which maternal gut commensal bacteria across the intestinal barrier to the lymph/blood circulation, reaching the mammary gland epithelium.…”