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

Infant gut microbiota development affects lifelong host physiology, and short-chain fatty acids (SCFAs) are promising key metabolites mediating the microbiota-host relationship. However, early-life gut SCFA patterns and their relationships with the gut microbiota remain unexplored. Here, we investigated the early-life gut microbiota development, SCFA profiles, and their relationship in dense longitudinally collected samples from 12 subjects (n = 1,048). Our results revealed that SCFA profiles exhibited three distinct phases of progression: an early phase characterised by low acetate and high succinate, a middle phase characterised by high lactate and formate, and a late phase characterised by high propionate and butyrate. The results also indicated that breast feeding and colonisation of fucosylated HMO-utilising bifidobacteria induced lactate and formate production in gut ecosystems, and that elevated faecal butyrate is associated with increased Clostridiales, genes for butyrate production, and breast-feeding cessation. Thus, our study shed light on the early-life gut SCFA-microbiota relationship, thereby providing a basis for developing strategies to modulate the key metabolite, which has been associated with host health.