Bifidobacteria are one of the major components in human microbiota that are suggested to function in maintaining human health. The colonization and cell number of Bifidobacterium species in human intestine vary with ageing. However, sequential changes of Bifidobacterium species ranging from newborns to centenarians remain unresolved. Here, we investigated the gut compositional changes of Bifidobacterium species over a wide range of ages. Faecal samples of 441 healthy Japanese subjects between the ages of 0 and 104 years were analysed using real-time PCR with species-specific primers. B. longum group was widely detected from newborns to centenarians, with the highest detection rate. B. breve was detected in approximately 70% of children under 3 years old. B. adolescentis and B. catenulatum groups were predominant after weaning. B. bifidum was detected at almost all ages. The detection rate of B. dentium was higher in the elderly than in other ages. B. animalis ssp. lactis was detected in 11.4% of the subjects and their ages were restricted. B. gallinarum goup was detected in only nine subjects, while B. minimum and B. mongoliense were undetected at any age. The presence of certain Bifidobacterium groups was associated with significantly higher numbers of other Bifidobacterium species/subspecies. Inter-species correlations were found among each species, exception for B. animalis ssp. lactis. These results revealed the patterns and transition points with respect to compositional changes of Bifidobacterium species that occur with ageing, and the findings indicate that there may be symbiotic associations between some of these species in the gut microbiota.

Previous studies have shown that Japanese people exhibit a higher abundance of Bifidobacterium compared to people from other countries. Among the possible factors affecting the gut microbiota composition, an association of functional lactase gene variants with a higher abundance of Bifidobacterium in the gut has been proposed in some reports. However, no Japanese subjects were included in these studies. In this study, we investigated the possible contribution of functional lactase loci to the high abundance of Bifidobacterium in Japanese populations. Based on a data analysis assessing 1,068 healthy Japanese adults, a number of subjects is at least seven times greater than that reported in available online data. all subjects possessed CC genotype at rs4988235 and the GG at rs182549, which are associated with low lactase activity. We observed a positive correlation between dairy product intake and Bifidobacterium abundance in the gut. Considering previous reports, which revealed that four additional functional lactase loci, rs145946881, rs41380347, rs41525747 and rs869051967 (ss820486563), are also associated with low lactase activity in Japanese people, our findings imply the possible contribution of host genetic variation-associated low lactase activity to the high abundance of Bifidobacterium in the Japanese population.

Characteristic bile duct and gut microbiota have been identified in patients with chronic biliary tract disease. This study aimed to characterize the fecal and bile microbiota in biliary tract cancer (BTC) patients and their relationship. Patients with BTC (n = 30) and benign biliary disease (BBD) without cholangitis (n = 11) were included. Ten healthy, age-matched subjects were also recruited for fecal microbiota comparison. The fecal and bile duct microbiotas were analyzed by sequencing the 16S rRNA gene V3-V4 region. Live bacteria were obtained in the bile from three BTC patients by culture, and metagenomics-based identification was performed. Linear discriminant analysis effect size showed a higher Enterobacteriaceae abundance and a lower Clostridia abundance, including that of Faecalibacterium and Coprococcus, in the BTC patients than in the other subjects. Ten of 17 operational taxonomic units (OTUs) assigned to Enterobacteriaceae in the bile were matched with the OTUs found in the BTC subject fecal samples. Furthermore, a bile-isolated strain possessed the carcinogenic bacterial colipolyketide synthase-encoding gene. Enterobacteriaceae was enriched in the BTC feces, and more than half of Enterobacteriaceae in the bile matched that in the feces at the OTU level. Our data suggests that fecal microbiota dysbiosis may contribute to BTC onset.

Previous clinical studies have shown that heat-killed Lacticaseibacillus paracasei MCC1849 suppresses subjective symptoms among healthy adults. However, the mechanism underlying this beneficial effect remains unclear. This clinical study aimed to investigate the effects of MCC1849 on immune functions in humans. In this randomized, double-blind, placebo-controlled, parallel-group study, 100 healthy adults were randomly divided into MCC1849 or placebo groups. Participants ingested test powder with 5 × 10¹⁰ MCC1849 cells or placebo powder for 4 weeks. Immune functions were evaluated using expression levels of CD86 and HLA-DR on dendritic cells (DCs), neutrophils, and natural killer cells. The expression levels of interferon (IFN)-α, -β, and -γ in peripheral blood mononuclear cells incubated with Cpg2216 in vitro were quantified. Efficacy analysis was performed on participants in the per-protocol set (placebo group; n = 47, MCC1849 group; n = 49). The expression level of CD86 on pDCs and the gene expression levels of IFN-α, -β, and -γ upon TLR9 agonist stimulation were significantly higher in the MCC1849 group at 4 weeks. No side effects were observed. This is the first report to show the positive effects of MCC1849 on human immune cells. These findings reveal one possible mechanism of how MCC1849 suppresses subjective symptoms.

Visceral fat accumulation is considered to be associated with a higher risk of chronic diseases. We investigated the effects of Bifidobacterium longum subsp. longum (B. longum) BB536 and Bifidobacterium breve (B. breve) MCC1274 on body composition, including visceral fat, in a randomized, parallel-group, placebo-controlled study. Participants were between 29 and 64 years of age and had a body mass index (BMI) of greater than 23 and less than 30. One hundred participants were randomly assigned to the probiotics group or placebo group. Participants were administered probiotic capsules containing 1 × 10¹⁰ colony-forming units (CFUs) of B. longum BB536 and 5 × 10⁹ CFU of B. breve MCC1274 or placebo capsules without bifidobacteria for 16 weeks. In the probiotics group, abdominal visceral fat area, total abdominal fat area, and serum triglyceride levels were significantly decreased compared to those in the placebo group. Additionally, the increase in BMI observed in the placebo group was significantly suppressed in the probiotics group. This study showed that B. longum BB536 and B. breve MCC1274 reduced abdominal visceral fat and total fat levels in healthy normal and overweight adults, suggesting their beneficial effects on body composition.

The interaction between the gut microbiota and the host can influence the host’s immune system. Bifidobacterium, a commensal genus of gut bacteria, seems to have positive effects on host health. Our previous clinical research showed that B. longum subsp. longum BB536 enhanced innate and adaptive immune responses in elderly individuals with a lower grade of immunity, but the immunomodulatory mechanism is still unclear. In this study, dendritic cell (DC) surface markers in peripheral blood mononuclear cells isolated from healthy individuals were evaluated through coculture with heat-killed BB536. DC markers, innate immune activity and cytokine levels in plasma were also evaluated by a randomized, double-blind, placebo-controlled, parallel-group study (UMIN000045564) with 4 weeks of continuous live BB536 intake. BB536 significantly increased the expression of CD86 and HLA-DR on plasmacytoid DCs (pDCs) in vitro. Compared to placebo (n = 48), a significant increase in the expression of CD86 on peripheral pDCs was detected at week 4 of live BB536 intake (n = 49; 1 × 10¹⁰ CFU/day). Furthermore, coculture with hk-BB536 significantly increased the IFNγ expression level and demonstrated trends of increased IFNα1 and IFNβ expression. These findings suggest that consumption of BB536 has potential immunomodulatory effects on healthy individuals through the activation of peripheral pDCs.