Aging is recognized as a common risk factor for many chronic diseases and functional decline. The newly emerging field of geroscience is an interdisciplinary field that aims to understand the molecular and cellular mechanisms of aging. Several fundamental biological processes have been proposed as hallmarks of aging. The proposition of the geroscience hypothesis is that targeting holistically these highly integrated hallmarks could be an effective approach to preventing the pathogenesis of age-related diseases jointly, thereby improving the health span of most individuals. There is a growing awareness concerning the benefits of the prophylactic use of probiotics in maintaining health and improving quality of life in the elderly population. In view of the rapid progress in geroscience research, a new emphasis on geroscience-based probiotics is in high demand, and such probiotics require extensive preclinical and clinical research to support their functional efficacy. Here we propose a new term, “gerobiotics”, to define those probiotic strains and their derived postbiotics and para-probiotics that are able to beneficially attenuate the fundamental mechanisms of aging, reduce physiological aging processes, and thereby expand the health span of the host. We provide a thorough discussion of why the coining of a new term is warranted instead of just referring to these probiotics as anti-aging probiotics or with other similar terms. In this review, we highlight the needs and importance of the new field of gerobiotics, past and currently on-going research and development in the field, biomarkers for potential targets, and recommended steps for the development of gerobiotic products. Use of gerobiotics could be a promising intervention strategy to improve health span and longevity of humans in the future.
The gut microbiota resides in the human gastrointestinal tract, where it plays an important role in maintaining host health. Recent advancements in next-generation sequencing methods have revealed the link between dysbiosis (imbalance of the normal gut microbiota) and several diseases, as this imbalance can disrupt the symbiotic relationship between the host and associated microbes. Establishment of the gut microbiota starts in utero or just after birth, and its composition dramatically changes to an adult-like composition by 3 years of age. Because dysbiosis during childhood may persist through adulthood, it is crucial to acquire a balanced gut microbiota in childhood. Therefore, current studies have focused on the factors affecting the infant gut microbiota. This review discusses recent findings, including those from our studies, on how various factors, including the delivery mode, feeding type, and administration of drugs, including antibiotics, can influence the infant gut microbiota. Here, we also address future approaches for the prevention and restoration of dysbiosis in children.
Comparisons of the changes in the gut microbiota and transcriptomes as a result of changes in diet have demonstrated that the regulation of the gene functions of intestinal bacteria is fundamental for the regulation of the intestinal environment. However, the functions of only about half of the genes can be predicted using nucleotide sequences obtained from the metagenomic data of the human gut microbiota. Therefore, the regulation of gut bacterial gene functions is hindered. To resolve this issue, the functions of the genes of intestinal bacteria must be identified. In our previous study, a high-throughput cultivation system was established for the dominant species of indigenous human intestinal microbiota. Using this system, we analyzed the synthesis and transport of polyamines by intestinal bacteria. Comparison of the results with those obtained by in silico analysis indicated the existence of novel polyamine synthetic enzymes and transport proteins. Next, strains with gene deletions and complementation for the polyamine synthetic system of the genus Bacteroides were analyzed. Furthermore, we co-cultured genetically engineered Escherichia coli and Enterococcus faecalis strains to demonstrate the presence of a polyamine synthetic pathway spanning multiple bacterial species. Here, we outline the trends of research using genetically engineered intestinal bacteria and the ripple effects of studies in which intestinal bacteria have been analyzed genetically. Moreover, because studies on intestinal bacteria at the gene level are indispensable for improving our understanding of their regulation, the importance of this research will continue to increase in the future.
We report the isolation of bacteria capable of degrading milk oligosaccharides from suckling infant rats. The bacteria were successfully isolated via a selective enrichment method, in which the serially diluted intestinal contents of infant rats were individually incubated in an enrichment medium containing 3′-sialyllactose (3′-SL), followed by the isolation of candidate strains from streaked agar plates and selection of 3′-SL-degrading strains using thin-layer chromatography. Subsequent genomic and phenotypic analyses identified all strains as Enterococcus gallinarum. The strains were capable of degrading both 3′-SL and 6′-SL, which was not observed with the type strain of E. gallinarum used as a reference. Furthermore, a time-course study combining high-performance anion-exchange chromatography with pulsed amperometric detection revealed that the representative strain AH4 degraded 3′-SL completely to yield an equimolar amount of lactose and an approximately one-fourth equimolar amount of sialic acid after 24 hr of anaerobic incubation. These findings point to a possibility that the enterococci degrade rat milk oligosaccharides to “cross-feed” their degradants to other members of concomitant bacteria in the gut of the infant rat.
Lactobacillus acidophilus surface layer proteins (SLPs) self-assemble into a monolayer that is non-covalently bound to the outer surface of the cells. There they are in direct contact with the environment, environmental stressors and gut components of the host in which the organism resides. The role of L. acidophilus SLPs is not entirely understood, although SLPs seem to be essential for bacterial growth. We constructed three L. acidophilus L-92 strains, each expressing a mutant of the most abundant SLP, SlpA. Each carried a 12-amino acid c-myc epitope substitution at a different position in the protein. A strain was also obtained that expressed the SlpA paralog SlpB from an originally silent slpB gene. All four strains behaved differently with respect to growth under various stress conditions, such as the presence of salt, ox gall or ethanol, suggesting that SlpA affects stress tolerance in L. acidophilus L-92. Also, the four mutants showed differential in vitro binding ability to human host cell proteins such as uromodulin or dendritic cell (DC)-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN). Furthermore, co-culture of murine immature DCs with a mutant strain expressing one of the recombinant SlpA proteins changed the concentrations of the cytokines IL-10 and IL-12. Our data suggest that SlpA and SlpB of L. acidophilus participate in bacterial stress tolerance and binding to uromodulin or DC-SIGN, possibly leading to effective immune-modification.
Bacterial RNA has recently emerged as an immune-stimulating factor during viral infection. The immune response in an organism is directly related to the progression of virus infections. Lactic acid bacteria in particular have anticancer, bioprotective, and antiallergic effects by modulating immunity. Here, we aimed to demonstrate the effect of bacterial RNA on in vitro production of IL-12, a proinflammatory cytokine, and on in vivo activity against influenza A virus (IFV) infection. Oral administration of heat-killed Enterococcus faecalis KH2 (KH2) or Lactobacillus plantarum SNK12 (SNK) in IFV-infected mice suppressed viral replication and stimulated production of virus-specific antibodies. However, ribonuclease-treated KH2 or SNK abrogated the effect, reducing IL-12 production in vitro and anti-IFV effects in vivo. Taken together, KH2 or SNK showed antiviral effects in vivo when administered orally, and the RNAs of KH2 and SNK play a part in these effects, despite the phylogenetic differences between the bacteria.
We investigated the gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) and its correlation with fibrosis and steatosis stratified by body mass index, as reflected in the controlled attenuation parameter and transient elastography values. A cross-sectional study was performed on 37 patients with NAFLD at Cipto Mangunkusumo National General Hospital from December 2018 to March 2019. The gut microbiota was investigated in fecal samples with 16S RNA sequencing using the MiSeq next-generation sequencing platform (Illumina). NAFLD was more common in patients with metabolic syndrome. Firmicutes, Bacteroidetes, and Proteobacteria were the predominant phyla. Bacteroides was more dominant than Prevotella, contrary to the results of previous studies on healthy populations in Indonesia. Microbiota dysbiosis was observed in most samples. The gastrointestinal microbiota diversity was significantly decreased in patients with NAFLD, high triglyceride levels, and central obesity. The Firmicutes/Bacteroidetes ratio correlated with steatosis and obesity, whereas some of the other species in lower taxonomy levels were mostly associated with steatosis and obesity without fibrosis. Proteobacteria was the only phylum strongly correlated with fibrosis in patients with an average body mass index. The gut microbiota diversity was decreased in patients with NAFLD, high triglyceride levels, and central obesity, and certain gut microbes were correlated with fibrosis and steatosis.
Adherence of probiotics to dietary fibers present in the intestinal tract may affect adhesion to intestinal epithelial cells. The properties of the adhesion of bifidobacteria to mucin or epithelial cells have been well studied; however, adhesion of bifidobacteria to dietary fiber has not been investigated. The adhesion ratio of six Bifidobacterium strains to cellulose and chitin was examined; among the strains, Bifidobacterium animalis subsp. lactis JCM 10602 showed high adherence to both cellulose and chitin, and two strains showed high adherence to only chitin. The ratios of adhesion of B. animalis to cellulose and chitin were positively and negatively correlated with ionic strength, respectively. These data suggest that hydrophobic and electrostatic interactions are involved in the adhesion to cellulose and chitin, respectively. The adhesion ratios of the cells in the late logarithmic phase to cellulose and chitin decreased by approximately 40% and 70% of the cells in the early logarithmic phase, respectively. Furthermore, the adhesion ratio to cellulose decreased with increasing bile concentration regardless of the culture phase of the cells. On the other hand, the adhesion ratio to chitin of cells in the early logarithmic phase decreased with increasing bile concentration; however, that of cells in the late logarithmic phase increased slightly, suggesting that adhesins differ depending on the culture phase. Our results indicated the importance of considering adhesion to both dietary fibers and the intestinal mucosa when using bifidobacteria as probiotics.
Various studies have suggested that the gut microbiome interacts with the host and may have a significant role in the aetiology of obesity and Type 2 Diabetes (T2D). It was hypothesised that bacterial communities in obesity and T2D differ from control and compromise normal interactions between host and microbiota. Obesity and T2D were developed in rats by feeding a high-fat diet or a high-fat diet plus a single low-dose streptozotocin administration, respectively. The microbiome profiles and their metabolic potentials were established by metagenomic 16S rRNA sequencing and bioinformatics. Taxonomy and predicted metabolism-related genes in obesity and T2D were markedly different from controls and indeed from each other. Diversity was reduced in T2D but not in Obese rats. Factors likely to compromise host intestinal, barrier integrity were found in Obese and T2D rats including predicted, decreased bacterial butyrate production. Capacity to increase energy extraction via ABC-transporters and carbohydrate metabolism were enhanced in Obese and T2D rats. T2D was characterized by increased proinflammatory molecules. While obesity and T2D show distinct differences, results suggest that in both conditions Bacteroides and Blautia species were increased indicating a possible mechanistic link.
Ogimi is one of Japan’s longevity villages and is located in Okinawa Prefecture. In this study, we focused on the elderly women living in the village, classified them into two groups based on whether or not they lived in Ogimi during the first 3 years of their lives, and compared the gut microbiota between the two groups. There were no differences in alpha and beta diversity; however, we found that the elderly women who lived in Ogimi during the first 3 years of their lives had a higher rate of Akkermansia muciniphila colonization in their guts.
Although bifidobacteria are already widely used as beneficial microbes with health-promoting effects, their amino acid utilization and metabolism are not yet fully understood. Knowledge about the metabolism of sulfur-containing amino acids in bifidobacteria is especially limited. In this study, we tested the methionine utilization ability of several bifidobacterial strains when it was the sole available sulfur source. Although bifidobacteria have long been predominantly considered to be cysteine auxotrophs, we showed that this is not necessarily the case.