Fucosylated human milk oligosaccharide-utilizing bifidobacteria regulate the gut organic acid profile of infants.

Bifidobacteria are the predominant bacteria in the infant gut and have beneficial effects on host physiology. Infant cohort studies have demonstrated that a higher abundance of bifidobacteria in the gut is associated with a reduced risk of disease. Recently, bifidobacteria-derived metabolites, such as organic acid, have been suggested to play crucial roles in host physiology. This review focuses on an investigation of longitudinal changes in the gut microbiota and organic acid concentrations over 2 years of life in 12 Japanese infants and aims to identify bifidobacteria that contribute to the production of organic acid in healthy infants. Acetate, lactate, and formate, which are rarely observed in adults, are characteristically observed during breast-fed infancy. Bifidobacterium longum subspecies infantis and the symbiosis of Bifidobacterium bifidum and Bifidobacterium breve efficiently produce these organic acids through metabolization of human milk oligosaccharide (HMO) with different strategies. These findings confirmed that HMO-utilizing bifidobacteria play an important role in regulating the gut organic acid profiles of infants.

Characterization of Bifidobacterium kashiwanohense that utilizes both milk- and plant-derived oligosaccharides.

Bifidobacteria are prominent members of the human gut microbiota throughout life. The ability to utilize milk- and plant-derived carbohydrates is important for bifidobacterial colonization of the infant and adult gut. The Bifidobacterium catenulatum subspecies kashiwanohense (B. kashiwanohense) was originally isolated from infant feces. However, only a few strains have been described, and the characteristics of this subspecies have been poorly investigated. Here, we characterized genotypes and phenotypes of 23 B. kashiwanohense-associated strains, including 12 newly sequenced isolates. Genome-based analysis clarified the phylogenetic relationship between these strains, revealing that only 13 strains are genuine B. kashiwanohense. We defined specific marker sequences and investigated the worldwide prevalence of B. kashiwanohense based on metagenome data. This revealed that not only infants but also adults and weaning children harbor this subspecies in the gut. Most B. kashiwanohense strains utilize long-chain xylans and possess genes for extracellular xylanase (GH10), arabinofuranosidase and xylosidase (GH43), and ABC transporters that contribute to the utilization of xylan-derived oligosaccharides. We also confirmed that B. kashiwanohense strains utilize short- and long-chain human milk oligosaccharides and possess genes for fucosidase (GH95 and GH29) and specific ABC transporter substrate-binding proteins that contribute to the utilization of a wide range of human milk oligosaccharides. Collectively, we found that B. kashiwanohense strains utilize both plant- and milk-derived carbohydrates and identified key genetic factors that allow them to assimilate various carbohydrates.

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

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.

Xylan utilisation promotes adaptation of Bifidobacterium pseudocatenulatum to the human gastrointestinal tract.

Dietary carbohydrates impact the composition of the human gut microbiota. However, the relationship between carbohydrate availability for individual bacteria and their growth in the intestinal environment remains unclear. Here, we show that the availability of long-chain xylans (LCX), one of the most abundant dietary fibres in the human diet, promotes the growth of Bifidobacterium pseudocatenulatum in the adult human gut. Genomic and phenotypic analyses revealed that the availability of LCX-derived oligosaccharides is a fundamental feature of B. pseudocatenulatum, and that some but not all strains possessing the endo-1,4-ß-xylanase (BpXyn10A) gene grow on LCX by cleaving the xylose backbone. The BpXyn10A gene, likely acquired by horizontal transfer, was incorporated into the gene cluster for LCX-derived oligosaccharide utilisation. Co-culturing with xylanolytic Bacteroides spp. demonstrated that LCX-utilising strains are more competitive than LCX non-utilising strains even when LCX-derived oligosaccharides were supplied. In LCX-rich dietary interventions in adult humans, levels of endogenous B. pseudocatenulatum increased only when BpXyn10A was detected, indicating that LCX availability is a fitness determinant in the human gut. Our findings highlight the enhanced intestinal adaptability of bifidobacteria via polysaccharide utilisation, and provide a cornerstone for systematic manipulation of the intestinal microbiota through dietary intervention using key enzymes that degrade polysaccharide as biomarkers.

A key genetic factor for fucosyllactose utilization affects infant gut microbiota development.

Recent studies have demonstrated that gut microbiota development influences infants' health and subsequent host physiology. However, the factors shaping the development of the microbiota remain poorly understood, and the mechanisms through which these factors affect gut metabolite profiles have not been extensively investigated. Here we analyse gut microbiota development of 27 infants during the first month of life. We find three distinct clusters that transition towards Bifidobacteriaceae-dominant microbiota. We observe considerable differences in human milk oligosaccharide utilization among infant bifidobacteria. Colonization of fucosyllactose (FL)-utilizing bifidobacteria is associated with altered metabolite profiles and microbiota compositions, which have been previously shown to affect infant health. Genome analysis of infants' bifidobacteria reveals an ABC transporter as a key genetic factor for FL utilization. Thus, the ability of bifidobacteria to utilize FL and the presence of FL in breast milk may affect the development of the gut microbiota in infants, and might ultimately have therapeutic implications.