The composition of the infant microbiota has a great impact on infant health, but its controlling factors are still incompletely understood. The frequently dominant anaerobic Bifidobacterium species benefit health, e.g., they can keep harmful competitors under control and modulate the intestinal immune response.

The human intestinal microbiome starts to form immediately after birth, and can greatly influence the health of the infant. During the first days facultative anaerobic species generally dominate, followed by a dominance of strictly anaerobic species, particularly Bifidobacterium species. An early transition to Bifidobacterium is associated with health benefits. To study the mechanisms of this transition and its hypothesised relation to oxygen, we introduce a multiscale mathematical model that considers metabolism, spatial bacterial population dynamics and resource sharing. Based on publicly available metabolic network data, the model predicts that differences in oxygen availability explain some of the observed individual variation in succession to anaerobic species. The model also predicts that anaerobic Bifidobacterium species become dominant through metabolizing lactose with a suboptimal yield, but a higher anaerobic growth rate than its competitors. The current work is the first step towards a more comprehensive understanding of the formation of a steady state adult colonic microbiota.

Background: Natural enrichment of sn-2 palmitate content of infant formulae by using bovine milk fat is known to reduce faecal fatty acid soap formation and improve stool consistency, but effects on gut microbiota composition are unknown. The purpose of this study was to test the influence of milk fat-based formula high in sn-2 palmitate on the infants’ gut microbiota composition and to confirm the beneficial effects of the formula on faecal composition and stool consistency. Methods: Twenty-two healthy term, formula-fed infants were enrolled in a single-blinded randomized, crossover, placebo-controlled trial. After a 2 week run in period, infants received either a 50% milk fat-based formula containing 39% sn-2 palmitate (MF) or a vegetable fat-based formula (VF) containing 10% sn-2 palmitate in a 2x2 week crossover design. Faecal microbiota composition was the primary outcome of the study. Other outcomes included faecal fatty acid soap excretion, calcium excretion, gut comfort parameters and faecal metabolites. Results: Microbiota analysis showed that bifidobacteria dominated the gut microbiota of most infants. Neither alpha- nor beta-diversity was significantly influenced by the intervention. The MF formula resulted in significantly lower faecal levels of palmitic acid soap and total fatty acid soaps than the VF formula (p<0.0002). Additionally, calcium excretion and palmitic acid concentration were significantly (p<0.05) lower in stool samples after MF intervention. Furthermore, a significant physiological effect on softer stools was observed in the MF intervention compared to the VF intervention (p=0.02). Of the 870 measured faecal metabolites, 263 were significantly different after MF and VF intervention (p<0.05). Most of these were found at higher levels after MF intervention, potentially indicative of the complex structure of milk fat. Metabolites with more than 2-fold change between interventions were mostly lipid-derived and included several milk fat-specific fatty acids. Conclusions: Replacing part of the vegetable fat in infant formula with bovine milk fat with high sn-2 palmitate levels did not change the microbiota composition, although a reduction in faecal palmitate soaps, total fatty acid soaps and calcium excretion while improving stool consistency in the MF intervention was confirmed. In addition, 263 faecal metabolites were significantly different, many related to the fat source. Trial registration: Netherlands Trial Registry Identifier: NL7815 19/06/2019

Background Natural enrichment of sn-2 palmitate content of infant formulae by using bovine milk fat is known to reduce formation of faecal fatty acid soaps and to improve stool consistency, but effects on gut microbiota composition are unknown. The purpose of this study was to test the influence of milk fat-based formula high in sn-2 palmitate on the infants’ gut microbiota composition and to confirm the beneficial effects of the formula on formation of faecal fatty acid soaps and stool consistency. Methods Twenty-two healthy term, formula-fed infants were enrolled in a single-blinded randomized, crossover, placebo-controlled trial. After a 2-week run-in period, infants received either a 50% milk fat-based formula containing 39% sn-2 palmitate (MF) or a vegetable fat-based formula (VF) containing 10% sn-2 palmitate in a 2 × 2-week crossover design. Faecal microbiota composition was the primary outcome of the study. Other outcomes included faecal fatty acid soap excretion, calcium excretion, gut comfort parameters and faecal metabolites. Results Microbiota analysis showed that bifidobacteria dominated the gut microbiota of most infants. Neither alpha- nor beta-diversity was significantly influenced by the intervention. Also, abundance of metabolic pathways was independent of the intervention. The MF formula resulted in significantly lower faecal levels of palmitic acid soap (p = 0.0002) and total fatty acid soaps (p = 0.0001) than the VF formula. Additionally, calcium excretion and palmitic acid concentration were significantly (p = 0.0335) lower in stool samples after MF intervention. Furthermore, a significant physiological effect on softer stools was observed in the MF intervention compared to the VF intervention (p = 0.02). Of the 870 measured faecal metabolites, 190 were significantly different after MF and VF intervention (FDR corrected p < 0.05). Most of these were found at higher levels after MF intervention, potentially indicative of the complex structure of milk fat. Metabolites with more than twofold change between interventions were mostly lipid-derived and included several milk fat-specific fatty acids. Conclusions Replacing part of the vegetable fat in infant formula with bovine milk fat with high sn-2 palmitate levels did not change the microbiota composition, although a reduction in faecal palmitate soaps, total fatty acid soaps and calcium excretion while improving stool consistency in the MF intervention was confirmed. In addition, 190 faecal metabolites were significantly different, many related to the fat source. Trial registration Netherlands Trial Registry Identifier: NL7815 19/06/2019.

A reduced capacity for butyrate production by the early infant gut microbiota is associated with negative health effects, such as inflammation and the development of allergies. Here we develop new hypotheses on the effect of the prebiotic galacto-oligosaccharides (GOS) or 2'-fucosyllactose (2'-FL) on butyrate production by the infant gut microbiota using a multiscale, spatiotemporal mathematical model of the infant gut. The model simulates a community of cross-feeding gut bacteria at metabolic detail. It represents the gut microbiome as a grid of bacterial populations that exchange intermediary metabolites, using 20 different subspecies-specific metabolic networks taken from the AGORA database. The simulations predict that both GOS and 2'-FL promote the growth of Bifidobacterium, whereas butyrate producing bacteria are only consistently abundant in the presence of propane-1,2-diol, a product of 2'-FL metabolism. The results suggest that in absence of prebiotics or in presence of only GOS, bacterial species, including Cutibacterium acnes and Bacteroides vulgatus, outcompete butyrate producers by feeding on intermediary metabolites. In presence of 2'-FL, however, production of propane-1,2-diol specifically supports butyrate producers.