Key bacterial taxa and metabolic pathways affecting gut short-chain fatty acid profiles in early life

Abstract

Infant gut microbiota development affects the host physiology throughout life, and short-chain fatty acids (SCFAs) are promising key metabolites mediating microbiota-host relationships. Here, we investigated dense longitudinally collected faecal samples from 12 subjects during the first 2 years (n = 1048) to identify early life gut SCFA patterns and their relationships with the microbiota. Our results revealed three distinct phases of progression in the SCFA profiles: early phase characterised by low acetate and high succinate, middle-phase characterised by high lactate and formate and late-phase characterised by high propionate and butyrate. Assessment of the SCFA–microbiota relationships revealed that faecal butyrate is associated with increased Clostridiales and breastfeeding cessation, and that diverse and personalised assemblage of Clostridiales species possessing the acetyl-CoA pathway play major roles in gut butyrate production. We also found an association between gut formate and some infant-type bifidobacterial species, and that human milk oligosaccharides (HMO)-derived fucose is the substrate for formate production during breastfeeding. We identified genes upregulated in fucose and fucosylated HMO utilisation in infant-type bifidobacteria. Notably, bifidobacteria showed interspecific and intraspecific variation in the gene repertoires, and cross-feeding of fucose contributed to gut formate production. This study provides an insight into early life SCFA–microbiota relationships, which is an important step for developing strategies for modulating lifelong health.

Human Milk Oligosaccharide-Stimulated Bifidobacterium Species Contribute to Prevent Later Respiratory Tract Infections

“…This observation indicates that an age-appropriate gut microbiome development may be important for protection against respiratory infection. In a recent study, Tsukuda et al reported SCFA and other organic acid profiles in stool samples during the first 2 years of age from a small cohort of mainly breastfed and vaginally born infants [ 51 ]. An early succinate peak was paralleled by increasing acetate, while propionate and butyrate increased with cessation of breastfeeding.…”

A multiscale spatiotemporal model including a switch from aerobic to anaerobic metabolism reproduces succession in the early infant gut microbiota

“…We cannot fully represent the complexities of the infant gut microbiota, and any generated hypotheses must necessarily be validated in in vitro and in vivo conditions. Detailed analysis of the infant microbiota has revealed a species composition that is much more diverse in both species and metabolites than our model results show [4, 64]. There is future work to be done to further study the relevant factors in the infant gut, and to bring these results into a more realistic model context.…”

“…Acetate and lactate are produced by Bifidobacterium spp in the characteristic bifid shunt, which produces acetate and lactate in a 3:2 ratio [15]. Formate, hydrogen, ethanol and succinate are also all reported in infant feces [9, 25, 59, 64].…”

Microbiota development in early life mediates association between mode of delivery and vaccine responses

“…Notably, we associated higher abundances of members of the Lachnospiraceae family, including butyrate-producing taxa, with higher anti-meningococcal antibody responses. The abundance of these bacteria in the gut typically increases following the cessation of breastfeeding 41,44 , and are generally found to be beneficial for the developing immune system 45 .…”