Functional Roles of B‐Vitamins in the Gut and Gut Microbiome

The gut microbiota produce hundreds of bioactive compounds, including B-vitamins, which play significant physiological roles in hosts by supporting the fitness of symbiotic species and suppressing the growth of competitive species. B-vitamins are also essential to the host and certain gut bacterium. Although dietary B-vitamins are mainly absorbed from the small intestine, excess B-vitamins unable to be absorbed in the small intestine are supplied to the distal gut. In addition, B-vitamins are supplied from biosynthesis by distal gut microbiota. B-vitamins in the distal colon may perform many important functions in the body; they act as (1) nutrients for a host and their microbiota, (2) regulators of immune cell activity, (3) mediators of drug efficacy, (4) supporters of survival, or the fitness of certain bacterium, (5) suppressors of colonization by pathogenic bacteria, and (6) modulators of colitis. Insights into basic biophysical principles, including the bioavailability of B-vitamins and their derivatives in the distal gut are still not fully elucidated. Here we briefly review the function of single B-vitamin in the distal gut including their roles in relation to bacteria. The prospect of extending analytical methods to better understand the role of B-vitamins in the gut is also explored

Current Understanding of the Gut Microflora in Subjects with Nutrition-Associated Metabolic Disorder Such as Obesity and/or Diabetes : Is There Any Relevance with Oral Microflora?

Purpose of review: The oral cavity is one of the main gateways to the whole body and leads to the gastrointestinal tract. Both oral cavity and gastrointestinal tract have complex ecosystems of microorganisms called microbiota. Recent studies have showed that altered local microbiome in human, such as gut microflora, is associated with various systemic diseases. This review focuses on the association between the microbiota at local sites, such as gut and oral cavity, and the systemic diseases, especially nutrition-associated metabolic disorder, such as obesity and/or diabetes. Recent findings: The gut microbiota has a potential for regulation in host immune system and metabolisms, such as energy, glucose and lipid, and is therefore an additional contributing environmental factor to the pathophysiology of obesity and diabetes as well as gut infectious inflammatory diseases. In addition, oral microorganisms play important roles as reservoirs for exacerbation of gut diseases and altered oral microbial profiles causing periodontal diseases, one of common oral infectious diseases, has been also associated with several systemic diseases including diabetes. Summary: It is necessary to consider that impaired oral microbiota, called oral dysbiosis, may affect the metabolic disorders leading to obesity and diabetes in addition to the gut inflammatory diseases via alteration of gut microflora. The relevance of oral microflora to gut dysbiosis leading to nutrition-associated metabolic disorder should be addressed as future investigations

Tenomodulin expression in the periodontal ligament enhances cellular adhesion.

Tenomodulin (Tnmd) is a type II transmembrane protein characteristically expressed in dense connective tissues such as tendons and ligaments. Its expression in the periodontal ligament (PDL) has also been demonstrated, though the timing and function remain unclear. We investigated the expression of Tnmd during murine tooth eruption and explored its biological functions in vitro. Tnmd expression was related to the time of eruption when occlusal force was transferred to the teeth and surrounding tissues. Tnmd overexpression enhanced cell adhesion in NIH3T3 and human PDL cells. In addition, Tnmd-knockout fibroblasts showed decreased cell adhesion. In the extracellular portions of Tnmd, the BRICHOS domain or CS region was found to be responsible for Tnmd-mediated enhancement of cell adhesion. These results suggest that Tnmd acts on the maturation or maintenance of the PDL by positively regulating cell adhesion via its BRICHOS domain

Daytime sleepiness in Japanese patients with multiple system atrophy: prevalence and determinants

BACKGROUND: The recent SLEEMSA study that evaluated excessive daytime sleepiness (EDS) in Caucasian patients with multiple system atrophy (MSA) demonstrated that EDS was more frequent in patients (28%) than in healthy subjects (2%). However, the prevalence and determinants of EDS in other ethnic populations have not been reported to date. METHODS: We performed a single-hospital prospective study on patients with probable MSA. To ascertain the prevalence and determinants of EDS in Japanese MSA patients, we assessed the patients’ degree of daytime sleepiness by using the Japanese version of the Epworth Sleepiness Scale (ESS). In addition, we investigated the effects of sleep-disordered breathing (SDB) and abnormal periodic leg movements in sleep (PLMS), which were measured by polysomnography, on the patients’ ESS scores. RESULTS: A total of 25 patients with probable MSA (21 patients with cerebellar MSA and 4 patients with parkinsonian MSA) were included in this study. All patients underwent standard polysomnography. The mean ESS score was 6.2 ± 0.9, and EDS was identified in 24% of the patients. SDB and abnormal PLMS were identified in 24 (96%) and 11 (44%) patients, respectively. The prevalences of EDS in patients with SDB and abnormal PLMS were 25% and 18%, respectively. No correlations were observed between ESS scores and the parameters of SDB or abnormal PLMS. CONCLUSIONS: The frequency of EDS in Japanese patients with MSA was similar to that in Caucasian MSA patients. SDB and abnormal PLMS were frequently observed in MSA patients, although the severities of these factors were not correlated with EDS. Further investigations using objective sleep tests need to be performed

Diarrhea induced by infection of Vibrio parahaemolyticus

Vibrio parahaemolyticus is a human pathogen that naturally inhabits marine and estuarine environments. Infection with V. parahaemolyticus is often associated with the consumption of raw or undercooked seafood, causing gastroenteritis with watery diarrhea. The presence of two type III secretion system (T3SS) proteins, thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH), has been closely associated with the severity of diarrheal illness. TDH and TRH have various biological activities including hemolytic activity, cardiotoxicity, and enterotoxicity. T3SS1 is involved in cytotoxicity to host cells and orchestrates a multifaceted host cell infection by induction of autophagy, cell rounding, and cell lysis. T3SS2 is thought to be related to the enterotoxicity of V. parahaemolyticus. The activities of inducing diarrhea of each of the virulence factors were summarized in this review

胎生期の低用量抗菌薬摂取が、子の腸内細菌叢や体脂肪組成に及ぼす影響

Several environmental factors during the prenatal period transgenerationally affect the health of newborns in later life. Because low-dose antibiotics have been used for promoting the growth of crops and livestock in agriculture, humans may have ingested residual antibiotics for several decades. However, the effect of prenatal administration of low-dose antibiotics on newborns’ health in later life is unclear. In the present study, we found that prenatal treatment of murine mothers with low-dose antibiotics increased the abundance of bacteria of the phylum Firmicutes and the genera Clostridium IV and XIVa in feces from pups. In addition, the body fat percentage of mice in the antibiotic-treated group was higher than those in the control group at 12 weeks of age even though all pups were fed a standard diet. The body fat percentage of all mice was correlated with the abundance of fecal bacteria of Clostridium IV and XIVa. These results predict that low-dose antibiotic administration during the prenatal period affects the gut microbiota of newborns and possibly their health in later life

New Function of Autophagy in C. jejuni Invasion

Campylobacter jejuni is a leading cause of food-borne disease worldwide. The pathogenicity of C. jejuni is closely associated with the internalization process in host epithelial cells, which is related to a host immune response. Autophagy indicates a key role in the innate immune system of the host to exclude invasive pathogens. Most bacteria are captured by autophagosomes and degraded by autophagosome-lysosome fusion in host cells. However, several pathogens, such as Salmonella and Shigella, avoid and/or escape autophagic degradation to establish infection. But autophagy involvement as a host immune response to C. jejuni infection has not been clarified. This study revealed autophagy association in C. jejuni infection. During infection, C. jejuni activated the Rho family small GTPase Rac1 signaling pathway, which modulates actin remodeling and promotes the internalization of this pathogen. In this study, we found the LC3 contribution to C. jejuni invasion signaling via the Rac1 signaling pathway. Interestingly, during C. jejuni invasion, LC3 was recruited to bacterial entry site depending on Rac1 GTPase activation just at the early step of the infection. C. jejuni infection induced LC3-II conversion, and autophagy induction facilitated C. jejuni internalization. Also, autophagy inhibition attenuated C. jejuni invasion step. Moreover, Rac1 recruited LC3 to the cellular membrane, activating the invasion of C. jejuni. Altogether, our findings provide insights into the new function of LC3 in bacterial invasion. We found the interaction between the Rho family small GTPase, Rac1, and autophagy-associated protein, LC3

Effects of Consuming Xylitol on Gut Microbiota and Lipid Metabolism in Mice

The sugar alcohol xylitol inhibits the growth of some bacterial species including Streptococcus mutans. It is used as a food additive to prevent caries. We previously showed that 1.5–4.0 g/kg body weight/day xylitol as part of a high-fat diet (HFD) improved lipid metabolism in rats. However, the effects of lower daily doses of dietary xylitol on gut microbiota and lipid metabolism are unclear. We examined the effect of 40 and 200 mg/kg body weight/day xylitol intake on gut microbiota and lipid metabolism in mice. Bacterial compositions were characterized by denaturing gradient gel electrophoresis and targeted real-time PCR. Luminal metabolites were determined by capillary electrophoresis electrospray ionization time-of-flight mass spectrometry. Plasma lipid parameters and glucose tolerance were examined. Dietary supplementation with low- or medium-dose xylitol (40 or 194 mg/kg body weight/day, respectively) significantly altered the fecal microbiota composition in mice. Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella, whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism

CFTR associated diarrhea in VP-infection

Vibrio parahaemolyticus is a foodborne bacterium that causes acute gastroenteritis through the consumption of contaminated, raw, or undercooked seafood. Cystic fibrosis transmembrane conductance regulator (CFTR) is a well-characterized chloride channel that regulates several other ion channels and transporters to maintain water homeostasis in the gut lumen. Also, CFTR is a main target of bacterial infection-associated diarrhea. Hence, the aim of this study was to clarify the contribution of CFTR in V. parahaemolyticus-induced diarrhea in a mouse model of intestinal loop fluid accumulation, with CFTR inhibitors and a CFTR knockout model. The results indicated that CFTR plays a critical role in fluid accumulation in response to V. parahaemolyticus infection. We also investigated the inflammatory association in CFTR-mediated V. parahaemolyticus-induced fluid secretion with cyclooxygenase inhibitors and found that fluid accumulation was decreased by inhibition of cyclooxygenase 2 produced by neutrophils. These findings suggest that V. parahaemolyticus-inducing infiltration and activation of neutrophils also participated in CFTR mediated fluid secretion. This study reveals an important relationship between V. parahaemolyticus-induced diarrhea and inflammation in a mouse model