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.

婴儿肠道微生物群的发育会影响整个生命过程中的宿主生理，而短链脂肪酸 (SCFA) 是有希望的关键代谢物，可介导微生物群与宿主的关系。在这里，我们调查了前 2 年（n = 1048) 以确定生命早期肠道 SCFA 模式及其与微生物群的关系。我们的研究结果揭示了 SCFA 谱中三个不同的进展阶段：以低乙酸盐和高琥珀酸盐为特征的早期阶段，以高乳酸和甲酸盐为特征的中期阶段以及以高丙酸盐和丁酸盐为特征的晚期阶段。对 SCFA-微生物群关系的评估表明，粪便丁酸盐与梭菌目增加和母乳喂养停止有关，并且具有乙酰辅酶 A 途径的梭菌目物种的多样化和个性化组合在肠道丁酸盐产生中起主要作用。我们还发现肠道甲酸盐和一些婴儿型双歧杆菌之间存在关联，并且人乳寡糖（HMO）衍生的岩藻糖是母乳喂养期间产生甲酸盐的底物。我们确定了婴儿型双歧杆菌中岩藻糖和岩藻糖基化 HMO 利用上调的基因。值得注意的是，双歧杆菌在基因库中表现出种间和种内变异，并且岩藻糖的交叉喂养有助于肠道甲酸的产生。这项研究提供了对生命早期 SCFA-微生物群关系的洞察，这是制定调节终生健康策略的重要一步。