Infant nutrition affects the microbiota-gut-brain axis: Comparison of human milk vs. infant formula feeding in the piglet model

Abstract

Early nutrition plays a dominant role in infant development and health. It is now understood that the infant diet impacts the gut microbiota and its relationship with gut function and brain development. However, its impact on the microbiota-gut-brain axis has not been studied in an integrative way. The objective here was to evaluate the effects of human milk (HM) or cow’s milk based infant formula (IF) on the relationships between gut microbiota and the collective host intestinal-brain axis. Eighteen 10-day-old Yucatan mini-piglets were fed with HM or IF. Intestinal and fecal microbiota composition, intestinal phenotypic parameters, and the expression of genes involved in several gut and brain functions were determined. Unidimensional analyses were performed, followed by multifactorial analyses to evaluate the relationships among all the variables across the microbiota-gut-brain axis. Compared to IF, HM decreased the α-diversity of colonic and fecal microbiota and modified their composition. Piglets fed HM had a significantly higher ileal and colonic paracellular permeability assessed by ex vivo analysis, a lower expression of genes encoding tight junction proteins, and a higher expression of genes encoding pro-inflammatory and anti-inflammatory immune activity. In addition, the expression of genes involved in endocrine function, tryptophan metabolism and nutrient transport was modified mostly in the colon. These diet-induced intestinal modifications were associated with changes in the brain tissue expression of genes encoding the blood-brain barrier, endocrine function and short chain fatty acid receptors, mostly in hypothalamic and striatal areas. The integrative approach underlined specific groups of bacteria (Veillonellaceae, Enterobacteriaceae, Lachnospiraceae, Rikenellaceae, and Prevotellaceae) associated with changes in the gut-brain axis. There is a clear influence of the infant diet, even over a short dietary intervention period, on establishment of the microbiota-gut-brain axis.

Microbiota from human infants consuming secretors or non-secretors mothers’ milk impacts the gut and immune system in mice

“…These data are in agreement with previous findings of higher microbial diversity in infants consuming infant formula compared to infants consuming human milk ( 38 ). Similarly, higher alpha diversity was observed in piglets fed dairy-based infant formula than those provided human milk ( 39 , 40 ). Bacteroides was one of the abundant genera in the mice colonized with microbiota from infants fed by secretor mothers (SMM).…”

Initial pig developmental stage influences intestinal organoid growth but not phenotype

“…Gene expression analysis was carried out using the Wafergen Smartchip cycler and Smartchip Multisample Nanodispenser (Biogenouest Genomics and the EcogenO core facility, Rennes, France). A house-designed dedicated set of porcine primers already described [16] was used, which allowed the analysis of the expression of 84 genes targeted on specific intestinal functions and of 12 housekeeping genes. The targeted genes were relative to the immune system, barrier function, endocrine function, digestion/nutrient transporters and tryptophan metabolism pathways.…”

Treatment of preterm brain injury via gut‐microbiota–metabolite–brain axis

“…HMOs Promote the colonization of beneficial bacteria, and improve the maturation of the intestinal epithelial barrier Improve cognitive development [118][119][120][121] Dietary fibers Regulate the GM diversity, facilitate recovery of SCFAsproducing bacteria, and promote BBB integrity Improve the behavioral deficits, synaptic damage, and cognitive performance [125,126] Dietary polyphenols Enrich beneficial bacteria, upregulate the expression of SCFAs…”

“…HMOs have been reported to optimize Bifidobacteriaceae and Bacteroidaceae colonization, suppress pathogen invasion, promote immune development, and regulate microbiota‐gut‐brain communication 117,118 . In a pig model fed with HMOs, HMO‐diet‐induced intestinal alterations were associated with changes in gene expression encoding the BBB, endocrine function, and SCFA receptors in brain tissue 119 . Another pig study showed that gut microbes could leverage metabolites produced by HMOs to induce structural changes in the brain and enhance cognitive function 120 .…”

“… 117 , 118 In a pig model fed with HMOs, HMO‐diet‐induced intestinal alterations were associated with changes in gene expression encoding the BBB, endocrine function, and SCFA receptors in brain tissue. 119 Another pig study showed that gut microbes could leverage metabolites produced by HMOs to induce structural changes in the brain and enhance cognitive function. 120 Additionally, human studies have demonstrated multiple roles for HMOs as modulators of the GM in children, influencers of colonization of Bifidobacteria in the infant gut, and facilitators of neonatal neurological development.…”