The gut microbiota has nutritional and protective functions. In patients with end-stage renal disease, changes in the gut microbiota disrupt their protective functions. Probiotics help maintain normal bowel function. However, their role in patients with end-stage renal disease is controversial. We investigated whether Clostridium butyricum affects the nutrition and immune function of patients with end-stage renal disease undergoing maintenance dialysis between 2014 and 2015; thirty-seven patients were included. The patients were divided into two groups: one in which C. butyricum was administered and one in which it was not. One tablet of the probiotics, which contained 20 mg of C. butyricum, was administered orally three times daily for 2 years in the C. butyricum group. The 16S rRNA genes were sequenced from stool samples of 14 (37.8%) patients in the C. butyricum group and 23 (62.2%) patients in the control group. The differences in the gut microbiota of the two groups were analyzed. The α-diversity index indicated that the C. butyricum group had significantly more operational taxonomic units and higher albumin and transferrin levels than the control group. The effector to target cell ratio was significantly higher in the C. butyricum group. In addition, interleukin-6 levels were significantly lower in the C. butyricum group, and inflammation was less severe in this group. The patients undergoing maintenance dialysis with C. butyricum had abundant gut microbiota. They also had a good nutritional status, low systemic inflammation, and a good immunological status.
The therapeutic effect of Clostridium butyricum for adults with Clostridioides difficile infection (CDI) was investigated. A retrospective study was conducted in medical wards of Tainan Hospital, Ministry of Health and Welfare, between January 2013 and April 2020. The disease severity of CDI was scored based on the Clinical Practice Guidelines of the IDSA/SHEA. Treatment success was defined as the resolution of diarrhea within six days of a therapeutic intervention without the need to modify the therapeutic regimen. In total, 241 patients developed CDI during hospitalization in the study period. The treatment success rates for the 99 patients with mild-moderate CDI among them were as follows: metronidazole, 69.4%; C. butyricum, 68.2%; metronidazole plus C. butyricum, 66.7%; and oral vancomycin, 66.7% (p=1.00). Patients with treatment success were less likely to have diabetes mellitus than those with treatment failure (38.2% vs. 61.3%, p=0.05). Patients treated with C. butyricum alone or in combination with metronidazole had shorter durations of diarrhea than those treated with metronidazole alone (3.1 ± 2.0 days or 3.5 ± 2.4 days vs. 4.2 ± 3.5 days; p=0.43 or 0.71), although the differences were not statistically significant. In conclusion, the treatment success rate of C. butyricum alone or in combination with metronidazole for patients with CDI was non inferior to that of metronidazole alone. The presence of diabetes mellitus in affected individuals is a risk factor for treatment failure.
Imbalance of the gut microbiota plays an important role in the pathogenesis of various diseases. Although many clinical studies have analyzed the gut microbiota, the definition of normal gut microbiota remains unclear. In this study, we aim to establish the average gut microbiota in the healthy Japanese population. Using 16S ribosomal RNA gene sequencing, we analyzed gut microbial data from fecal samples obtained from 6,101 healthy Japanese individuals. Based on their ages, the individuals were divided into three groups: young, middle-age, and old. Individuals were further categorized according to body mass index (BMI) into lean, normal, and obese groups. The α and β diversities in the old group were significantly higher than those in the young and middle-age groups. The Firmicutes/Bacteroidetes ratio of subjects in the obese category was significantly lower compared with those of subjects in the lean and normal categories in the young and middle-age groups. Genus Bacteroides was the dominant gut microbiota across all the BMI categories in all the age groups. Among the top ten genera, the abundances of Bacteroides, Bifidobacterium, Anaerostipes, Blautia, Dorea, Fusicatenibacter, Lachnoclostridium, and Parabacteroides were significantly lower in the old group than in the young and middle-age groups. The correlation network at the genus level revealed different microbe-microbe interactions associated with age and BMI. We determined the average Japanese gut microbiota, and this information could be used as a reference. The gut microbiota greatly differs based on the life stage and metabolic status of the host, and this gives rise to a variety of host–gut microbe interactions that can lead to an increased susceptibility to disease.
Although lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase protein mainly produced by hepatocytes, it has also been proposed to be a pro-inflammatory adipokine. Obesity and the consumption of a high-fat diet (HFD) are reportedly associated with elevated levels of LPS in plasma and free fatty acids (FFAs) in white adipose tissue (WAT). We examined whether circulating LPS or local FFAs are responsible for the HFD-induced increase of LBP in WAT. Male C57BL/6J mice were fed either a normal-fat diet (NFD) or an HFD. The mRNA levels in the liver and mesenteric WAT (mWAT), total FFA content in mWAT, and LBP and LPS concentrations in plasma were determined. The Lbp mRNA level in mWAT was higher in mice fed the HFD than in those fed the NFD for 3, 7, or 28 days or 14 weeks, whereas the hepatic Lbp mRNA level did not differ between the groups. The Lbp mRNA level in mWAT was also increased by the HFD in germ-free mice, which do not have gut microbiota, the source of LPS. The plasma LPS level did not show a significant correlation with the mWAT Lbp mRNA level. The total FFA content in mWAT was higher in mice fed the HFD than in those fed the NFD and positively correlated with the Lbp mRNA level. Supplementation with palmitic acid increased the Lbp mRNA level in 3T3-L1 adipocytes. We propose that local FFAs, but not circulating LPS, are the trigger for increased Lbp expression in mWAT of mice fed the HFD.
Oxidative stress is associated with aging and pathologies such as cardiovascular diseases, Alzheimer’s disease, and cancer. Glutathione S-transferase (GST), a family of detoxification enzymes, plays a crucial role in countering oxidative stress. Therefore, there is a need for the development of physiologically functional foods and agricultural products, which enhance GST activity. Sesamin and episesamin are major lignans in refined sesame oil that exhibit beneficial properties including antioxidative stress effects. A previous study showed that sesamin upregulated GST activity. This study aimed to elucidate the mechanism underlying the GST activity enhancement elicited by sesame lignans. C57BL/6J mice were orally administered 20 mg/kg body weight sesame lignans (sesamin:episesamin=1:1) for 7 days. Oral administration of sesame lignans increased the GST activity in the mouse liver. Furthermore, the lignans upregulated GSTA1, GSTA4, and GSTM4 protein expression. Microarray analysis revealed that sesame lignans changed the expression of various microRNAs (miRNAs) (84 upregulated, 19 downregulated). We also found 16 miRNAs, including miR-669c-3p, that may negatively regulate GST expression among the 19 miRNAs with reduced expression caused by the sesame lignans. miR-669c is reportedly negatively correlated with GST. Additionally, we transfected NMuLi cells with an miR-669c-3p mimic and evaluated the effect of miR-669c-3p on GST mRNA and protein expressions. The results showed that the miR-669c-3p mimic suppressed the mRNA and protein levels of GSTA4 and GSTM4. In conclusion, sesame lignans increased GST protein expression and activity and downregulated miRNAs, including miR-669c-3p, which is a possible suppressor of GST.
Pellagra is caused by an abnormal intake and/or use of niacin, but its phenotypes are diverse. The phenotypes of pellagra can also be atypical, such as nausea. We previously reported a mouse model of pellagra-related nausea. However, the mechanism of this model is unclear. In this study, we found that the gut microbiota, which is thought to be a source of niacin, played an important role in the development of pellagra-related nausea in germ-free mice. We also investigated the gut microbiome. We compared urinary niacin metabolite levels and the dermal response between mice fed a normal diet and those fed a low-niacin diet to investigate the putative trigger of pellagra. Epoxyeicosatrienoic and hydroxyeicosatetraenoic acid levels were higher in mice fed a low-niacin diet compared with those fed a normal diet. Furthermore, histological studies indicated a dermatological response to the low-niacin diet. Interestingly, higher levels of oxidised fatty acids in response to the germ-free state were also observed. These findings indicate successful establishment of our newly established mouse model of pellagra via the gut microbiota. We believe that this model could enable the discovery of the putative cause of pellagra and phenotypes of pellagra that have not been recognised yet.