Among rhesus macaques, mother-reared infants more quickly acquired adult-typical microbiota and had higher levels of beneficial commensal taxa compared with Cesarean-delivered, human-reared, formula-fed infants. These results, published in the Journal of Pediatric Gastroenterology and Nutrition, suggest that in counseling regarding delivery mode and feeding regimens, the infant gut microbiome should be considered.

Breastfeeding and vaginal delivery are among the most influential factors affecting the establishment of the gut microbiome in young infants. Using a nonhuman primate model, researchers assessed the benefits of exposure to both the mother and breast milk for microbial colonization and differences in infant growth.

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In total, 54 infant rhesus macaques were included in the study; 35 full-term, vaginally birthed infants were housed with their mothers and breastfed exclusively. Nineteen infants were delivered via Cesarean section, formula-fed, and human reared. Investigators obtained rectal swabs at 2, 4, or 8 weeks of age and extracted genomic DNA for analysis.

Ultimately, the rearing condition did have a significant effect on gut microbial community structure, with divergent gut microbiota at 2, 4, and 8 weeks. In human-reared infants, sample-to-sample phylogenetic distances were larger by 2 weeks of age, but community structure dissimilarities shifted to a larger difference in mother-reared infants at weeks 4 and 8 (t=2.99, 3.29, and 3.60, respectively).

Differences were apparent at all taxonomic levels, but were most prominent at the phylum and genus levels. The most abundant microbes were gram-positive Firmicutes and gram-negative Bacteroidetes phyla, similar to humans. However, the researchers did find that the Firmicutes-to-Bacteroidetes ratio was affected by rearing; Firmicutes were “relatively more abundant” in human-reared infants at 2, 4, and 8 weeks. Prevotella was the most consistently abundant genus in the mother-reared group (9.9%) vs 5% in human-reared infants at 2 weeks. Highest Prevotella levels were noted in mother-reared infants at 8 weeks — a similar abundance to adult monkeys.

Genus Blautia was more enriched among human-reared infants at 4 and 8 weeks (10.5% vs 3.9% and 9.4% vs 4.9%). This group also demonstrated a lower relative abundance of the phyla Actinobacteria, which was reflective of a significantly lower abundance of the genus Bifidobacterium at 2, 4, and 8 weeks. Bifidobacteria diminished over time in this group (0.2% and 0.15% at 4 weeks and 8 weeks vs 1% at 2 weeks).

Functional predictions for human-reared infants indicated pathway increases in terms of energy, carbohydrate and lipid metabolism, and xenobiotic biodegradation and metabolism. In contrast, increases in pathways associated with the metabolism of vitamins, terpenoids, polyketides, and amino acids were found in the mother-reared group.

The researchers used growth curve analysis to assess weight gain through 8 months of age. Overall, the growth trajectory of the human-reared group was faster. Human-reared infants weighed an average of 188 g more at 2 months, despite similar birth weights, and 88 g more at 4 months. At 6 months, weight differences diminished after the infants were transitioned to solid food.

The phylogenetic richness of microbial community structures at 8 weeks was positively associated with infant weight at the time of sampling (r=0.350) and was significantly correlated with subsequent weights at 4, 6, and 8 months (r=0.433, 0.408, and 0.418, respectively).

Limitations to the study included the use of an incubator in the human-reared group, as well as the small sample size.

“[F]indings concur with the view that there is a biological expectancy that a mother will be present to provide a sustained microbial inoculation,” the researchers concluded. “Although the improved composition of formula, including prebiotic factors, now allow it to more closely resemble mother’s milk, we still need to advance our understanding of its prebiotic functions.”

Reference

Rendina DN, Lubach GR, Phillips GJ, Lyte M, Coe CL. Maternal and breast milk influences on the infant gut microbiome, enteric health and growth outcomes of rhesus monkeys. J Pediatr Gastroenterol Nutr. 2019;69(3):363-369.