It has been reported that the composition of human gut microbiota changes with age; however, few studies have used molecular techniques to investigate the long-term, sequential changes in gut ...microbiota composition. In this study, we investigated the sequential changes in gut microbiota composition in newborn to centenarian Japanese subjects.
Fecal samples from 367 healthy Japanese subjects between the ages of 0 and 104 years were analyzed by high-throughput sequencing of amplicons derived from the V3-V4 region of the 16S rRNA gene. Analysis based on bacterial co-abundance groups (CAGs) defined by Kendall correlations between genera revealed that certain transition types of microbiota were enriched in infants, adults, elderly individuals and both infant and elderly subjects. More positive correlations between the relative abundances of genera were observed in the elderly-associated CAGs compared with the infant- and adult-associated CAGs. Hierarchical Ward's linkage clustering based on the abundance of genera indicated five clusters, with median (interquartile range) ages of 3 (0-35), 33 (24-45), 42 (32-62), 77 (36-84) and 94 (86-98) years. Subjects were predominantly clustered with their matched age; however, some of them fell into mismatched age clusters. Furthermore, clustering based on the proportion of transporters predicted by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) showed that subjects were divided into two age-related groups, the adult-enriched and infant/elderly-enriched clusters. Notably, all the drug transporters based on Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology groups were found in the infant/elderly-enriched cluster.
Our results indicate some patterns and transition points in the compositional changes in gut microbiota with age. In addition, the transporter property prediction results suggest that nutrients in the gut might play an important role in changing the gut microbiota composition with age.
ABSTRACT
Members of Bifidobacterium are among the first microbes to colonise the human gut, and certain species are recognised as the natural resident of human gut microbiota. Their presence in the ...human gut has been associated with health-promoting benefits and reduced abundance of this genus is linked with several diseases. Bifidobacterial species are assumed to have coevolved with their hosts and include members that are naturally present in the human gut, thus recognised as Human-Residential Bifidobacteria (HRB). The physiological functions of these bacteria and the reasons why they occur in and how they adapt to the human gut are of immense significance. In this review, we provide an overview of the biology of bifidobacteria as members of the human gut microbiota and address factors that contribute to the preponderance of HRB in the human gut. We highlight some of the important genetic attributes and core physiological traits of these bacteria that may explain their adaptive advantages, ecological fitness, and competitiveness in the human gut. This review will help to widen our understanding of one of the most important human commensal bacteria and shed light on the practical consideration for selecting bifidobacterial strains as human probiotics.
Bifidobacterial species that ubiquitously encounter in the human host, collectively known as the Human-Residential Bifidobacteria (HRB), possess unique genetic elements and superior physiological functions that contribute to their ecological fitness and competitiveness, and they are thus more beneficial to humans.
It has previously been shown that the consumption of probiotics may have beneficial effects not only on peripheral tissues but also on the central nervous system and behavior via the ...microbiota-gut-brain axis, raising the possibility that treatment with probiotics could be an effective therapeutic strategy for managing neurodegenerative disorders. In this study, we investigated the effects of oral administration of Bifidobacterium breve strain A1 (B. breve A1) on behavior and physiological processes in Alzheimer's disease (AD) model mice. We found that administration of B. breve A1 to AD mice reversed the impairment of alternation behavior in a Y maze test and the reduced latency time in a passive avoidance test, indicating that it prevented cognitive dysfunction. We also demonstrated that non-viable components of the bacterium or its metabolite acetate partially ameliorated the cognitive decline observed in AD mice. Gene profiling analysis revealed that the consumption of B. breve A1 suppressed the hippocampal expressions of inflammation and immune-reactive genes that are induced by amyloid-β. Together, these findings suggest that B. breve A1 has therapeutic potential for preventing cognitive impairment in AD.
The infant's gut microbiome is generally rich in the
genus. The mother's milk contains natural prebiotics, called human milk oligosaccharides (HMOs), as the third most abundant solid component after ...lactose and lipids, and of the different gut microbes, infant gut-associated bifidobacteria are the most efficient in assimilating HMOs. Indeed, the fecal concentration of HMOs was found to be negatively correlated with the fecal abundance of
in infants. Given these results, two HMO molecules, 2'-fucosyllactose and lacto-
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tetraose, have recently been industrialized to fortify formula milk. As of now, however, our knowledge about the HMO consumption pathways in infant gut-associated bifidobacteria is still incomplete. The recent studies indicate that HMO assimilation abilities significantly vary among different
species and strains. Therefore, to truly maximize the effects of prebiotic and probiotic supplementation in commercialized formula, we need to understand HMO consumption behaviors of bifidobacteria in more detail. In this review, we summarized how different
species/strains are equipped with varied gene sets required for HMO assimilation. We then examined the correlation between the abundance of the HMO-related genes and bifidobacteria-rich microbiota formation in the infant gut through data mining analysis of a deposited fecal microbiome shotgun sequencing dataset. Finally, we shortly described future perspectives on HMO-related studies.
Antigen-specific immunoglobulin (Ig) A plays a major role in host defense against infections in gut mucosal tissue. Follicular helper T (Tfh) cells are located in germinal centers and promote IgA ...production via interactions with germinal center B cells. Several studies have demonstrated that some lactic acid bacteria (LAB) strains activate the host's acquired immune system, inducing IgA secretion in the intestine. However, the precise molecular mechanisms underlying the effects of LAB on IgA production and Tfh cells are not fully resolved. Lactobacillus paracasei MCC1849 is a probiotic strain isolated from the intestine of a healthy adult. In this study, we investigated the effects of orally administered heat-killed MCC1849 on IgA production in the intestine and on Tfh cell induction in vivo. We found that orally administered MCC1849 induced antigen-specific IgA production in the small intestine, serum and lungs. We also observed that MCC1849 increased the proportion of IgA+ B cells and Tfh cells in Peyer's patches (PPs). In addition, MCC1849 increased the gene expression of IL-12p40, IL-10, IL-21, STAT4 and Bcl-6 associated with Tfh cell differentiation. These results suggest that orally administered MCC1849 enhances antigen-specific IgA production and likely affects Tfh cell differentiation in PPs.
Bifidobacterium longum subsp. longum represents one of the most prevalent bifidobacterial species in the infant, adult and elderly (human) gut. In the current study, we performed a comparative genome ...analysis involving 145 B. longum representatives, including 113 B. longum subsp. longum strains obtained from healthy Japanese subjects aged between 0 and 98 years. Although MCL clustering did not reveal any correlation between isolated strains and subject age, certain characteristics appear to be more prevalent among strains corresponding to specific host ages, such as genes involved in carbohydrate metabolism and environmental response. Remarkably, a substantial number of strains appeared to have been transmitted across family members, a phenomenon that was shown not to be confined to mother-infant pairs. This suggests that the ubiquitous distribution of B. longum subsp. longum across the human lifespan is at least partly due to extensive transmission between relatives. Our findings form a foundation for future research aimed at unraveling the mechanisms that allow B. longum strains to successfully transfer between human hosts, where they then colonize and persist in the gut environment throughout the host's lifespan.
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.
Accumulating evidence suggests a relationship between the gut microbiota and the development of obesity, indicating the potential of probiotics as a therapeutic approach. Bifidobacterium breve B-3 ...has been shown to exert anti-obesity effects in high-fat diet-induced obese mice. In the present study, the anti-obesity effects of the consumption of B. breve B-3 by healthy pre-obese (25 ≤ BMI < 30) adults were investigated in a randomized, double-blind, placebo-controlled trial (trial registration: UMIN-CTR No. 000023919; preregistered on September 2, 2016). Eighty participants were randomized to receive placebo or B. breve B-3 capsules (2 × 1010 CFU/day) daily for 12 weeks. The visceral fat area significantly increased at weeks 4 and 8 in the placebo group only; no significant change was observed in the B-3 group. Body fat mass and percent body fat were significantly lower in the B-3 group than in the placebo group at weeks 8 and 12 (p<0.05, ANCOVA adjusted with baseline values). Although no significant differences were observed in blood parameters between the groups, the intake of B. breve B-3 slightly decreased triglyceride levels and improved HDL cholesterol from the baseline. No serious adverse effects were noted in either group. These results suggest that the probiotic strain B. breve B-3 has potential as a functional food ingredient to reduce body fat in healthy pre-obese individuals.
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•Bifidobacterium longum BB536 is a multifunctional probiotic that is effective in alleviating gastrointestinal, immunological and infectious diseases.•Existing evidence imply that the ...multifunctional effects of BB536 are attributed to its ability to stabilize gut microbiota and improve the intestinal environment.•BB536 improves immune dysfunction by driving a fine-tuned homeostatic balance within the host-microbiome interaction.
Probiotics have shown great promise in promoting human health. Despite the promising evidence, there is little information on the clinical efficacy of many of the available probiotics and their mechanisms of action are often unclear. Bifidobacterium longum subsp. longum BB536 is a clinically effective, well-established, multifunctional probiotic that has a long history of human use in alleviating gastrointestinal, immunological and infectious diseases. This review summarizes the functional benefits of BB536 from the most relevant clinical and animal studies and offers a theoretical basis for understanding its mechanisms of action. Key clinical findings point out that BB536 could act as a microbiome modulator to orchestrate the physiological activities of gut communities. Specifically, BB536 modulates luminal metabolism, stabilizes gut microbiota, and ultimately drives a fine-tuned homeostatic balance within the host-microbiome interaction. Clinical evidence of effectiveness of BB536 and how such multifunctional activities take place would be valuable for an optimized probiotic selection.
The microscopic defects that distributed randomly in metals are not only hard to detect, but also may inevitably cause catastrophic failure. Thus, autonomic probing and healing for damage inside ...metals continue to be a challenging. Here we show a novel approach for self-healing using electropulsing as a stimulus to trigger repairing of damaged metals. This is achieved via a process that through expelling absolutely currents, the microcrack causes them to be redistributed to form a concentrated and a diluted region around it, thereby inducing an extremely high temperature gradient and a large compressive stress, which drive material flow to close microcracks. Simultaneously, a large enough heat for bonding atoms was produced. That is, the microcrack as an empty cavity can be regarded as a special micro-device to shape a localized microscopic energy field, which in turn activates a healing process. The microstructure and mechanical property verified the extrinsic self-healing of a titanium alloy. The process is performed on a short timescale, is enable to detect automatically and act directly on the internal defects in metals, and to heal damage without any healing agent, long time heating as well as applied high pressure, offering unique advantages over conventional healing approaches.
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