Gut microbiota affects the host's metabolism, and it is suggested that there are differences in gut microbiota composition between patients with type 2 diabetes and healthy individuals. Additionally, dysbiosis may increase the concentration of lipopolysaccharides (LPS), causing metabolic endotoxemia, which induces impaired glucose tolerance. Several studies have reported relationships between metabolic diseases and the gut microbiota; and prebiotics, such as oligosaccharides, are commonly consumed to regulate gut microbiotas in healthy individuals. Galacto-oligosaccharides (GOS) are a major prebiotic, which specifically increase Bifidobacteriaceae abundance. Recent studies have reported that Bifidobacteriaceae improved metabolic endotoxemia or impaired glucose tolerance. However, there are few studies reporting the effects of GOS on patients with type 2 diabetes. In the current study, we compared clinical parameters, faecal gut microbiota, their associated metabolic products and their components such as LPS, and LPS-binding protein (LBP) produced by the host, between patients with diabetes and healthy controls. We then assessed the effects of GOS on glycaemic control, and gut microbiotas and metabolites in patients with type 2 diabetes in a double-blind controlled manner. LBP levels were significantly higher in patients with diabetes than those of healthy subjects, which was consistent with previous reports. The abundance of Bifidobacteriaceae and the diversity of intestinal microbiota were significantly lower in patients with diabetes than in healthy subjects. Interestingly, Bifidobacteriaceae was markedly restored in patients with diabetes after consumption of GOS, whereas LBP and glucose tolerance did not improve during this short-term trial period. In the present study, we demonstrated that GOS can ameliorate dysbiosis in patients with diabetes, and continuous intake of GOS may be a promising method for managing type 2 diabetes.

We report here a functional analysis of spo5 ؉ (mug12 ؉ ) of Schizosaccharomyces pombe, which encodes a putative RNA-binding protein. The disruption of spo5 ؉ caused abnormal sporulation, generating inviable spores due to failed forespore membrane formation and the absence of a spore wall, as determined by electron microscopy. Spo5 regulates the progression of meiosis I because spo5 mutant cells display normal premeiotic DNA synthesis and the timely initiation of meiosis I but they show a delay in the peaking of cells with two nuclei, abnormal tyrosine 15 dephosphorylation of Cdc2, incomplete degradation of Cdc13, retarded formation and repair of double strand breaks, and a reduced frequency of intragenic recombination. Immunostaining showed that Spo5-green fluorescent protein (GFP) appeared in the cytoplasm at the horsetail phase, peaked around the metaphase I to anaphase I transition, and suddenly disappeared after anaphase II. Images of Spo5-GFP in living cells revealed that Spo5 forms a dot in the nucleus at prophase I that colocalized with the Mei2 dot. Unlike the Mei2 dot, however, the Spo5 dot was observed even in sme2⌬ cells. Taken together, we conclude that Spo5 is a novel regulator of meiosis I and that it may function in the vicinity of the Mei2 dot.

AbstractsTubulointerstitial injury is central to the progression of end‐stage renal disease. Recent studies have revealed that one of the most investigated uremic toxins, indoxyl sulfate (IS), caused tubulointerstitial injury through oxidative stress and endoplasmic reticulum (ER) stress. Because indole, the precursor of IS, is synthesized from dietary tryptophan by the gut microbiota, we hypothesized that the intervention targeting the gut microbiota in kidney disease with galacto‐oligosaccharides (GOS) would attenuate renal injury. After 2 weeks of GOS administration for 5/6 nephrectomized (Nx) or sham‐operated (Sham) rats, cecal indole and serum IS were measured, renal injury was evaluated, and the effects of GOS on the gut microbiota were examined using pyrosequencing methods. Cecal indole and serum IS were significantly decreased and renal injury was improved with decreased infiltrating macrophages in GOS‐treated Nx rats. The expression levels of ER stress markers and apoptosis were significantly increased in the Nx rats and decreased with GOS. The microbiota analysis indicated that GOS significantly increased three bacterial families and decreased five families in the Nx rats. In addition, the analysis also revealed that the bacterial family Clostridiaceae was significantly increased in the Nx rats compared with the Sham rats and decreased with GOS. Taken altogether, our data show that GOS decreased cecal indole and serum IS, attenuated renal injury, and modified the gut microbiota in the Nx rats, and that the gut microbiota were altered in kidney disease. GOS could be a novel therapeutic agent to protect against renal injury.

Arabinoxylan hydrolysates (AXH) are the hydrolyzed products of the major components of dietary fibers, arabinoxylan. AXH include diverse oligosaccharides varying in xylose polymerization and side residue modifications with arabinose at the O-2 and/or O-3 positions of the xylose unit. Previous studies have reported that AXH exhibit prebiotic properties on gut bifidobacteria; moreover, several adult-associated bifidobacterial species (e.g., Bifidobacterium adolescentis and Bifidobacterium longum ssp. longum) are known to utilize AXH. In this study, we tried to elucidate the molecular mechanisms of AXH utilization by Bifidobacterium pseudocatenulatum, which is a common bifidobacterial species found in adult feces. We performed RNA-seq transcriptomic analysis of B. pseudocatenulatum YIT 4072T, which identified three up-regulated gene clusters during AXH utilization. The gene clusters encoded three sets of ATP-binding cassette (ABC) transporters and five enzymes belonging to the glycoside hydrolase family 43 (GH43). By characterizing the recombinant proteins, we found that three solute-binding proteins of ABC transporters showed either broad or narrow specificity: two arabinofuranosidases hydrolyze either single- or double-decorated arabinoxylooligosaccharides: three xylosidases exhibited functionally identical activity. These data collectively suggest that the transporters and glycoside hydrolases, encoded in the three gene clusters, work together to utilize AXH of different sizes and side residue modifications. Thus, our study sheds light on the overall picture of how these proteins collaborate for utilization of AXH in B. pseudocatenulatum, and may explain the predominance of this symbiont species in the adult human gut. Importance Bifidobacteria commonly reside in the human intestine and possess abundant genes involved in carbohydrate utilization. Arabinoxylan hydrolysates (AXH) are hydrolyzed products of arabinoxylan, one of the most abundant dietary fibers, and they include xylooligosaccharides and those decorated with arabinofuranosyl residues. The molecular mechanism by which B. pseudocatenulatum, a common bifidobacterial species found in adult feces, utilizes structurally and compositionally variable AXH is yet to be extensively investigated. In this study, we identified three gene clusters (encoding five GH43 enzymes and three solute-binding proteins of ABC transporters) that were up-regulated in B. pseudocatenulatum YIT 4072T during AXH utilization. By investigating their substrate specificities, we revealed how these proteins are involved in the uptake and degradation of AXH. These molecular insights may provide a better understanding of how resident bifidobacteria colonize the colon.