Clostridioides difficile colonizes a polymicrobial environment in the intestine and is a causative agent for antibiotic-associated diarrhea (AAD) and pseudomembranous colitis (PMC). The most important virulence factors of C. difficile are bacterial toxins, and three toxins (toxin A, toxin B, and binary toxin) are produced by toxigenic strains. Other virulence factors include spores, flagella, capsules, biofilms, hydrolytic enzymes and adhesins. C. difficile infection (CDI) is specifically diagnosed by anaerobic culture and toxin detection by either nucleic acid amplification test (NAAT) or enzyme-linked immunosorbent assay (ELISA). For treatment of CDI, metronidazole, vancomycin and fidaxomicin are used based on the severity of CDI. Mutual interaction between C. difficile and gut microbiota is associated with pathogenesis of CDI, and decreased microbial diversity with altered gut microbiome was detected in CDI patients. Restoration of certain gut microbiota is considered to be potentially effective for the prevention and treatment of CDI, and an ideal goal for CDI patients is restoration of the gut microbiota to a healthy state. Fecal microbiota transplantation (FMT) is a highly successful method of microbiome restoration and has been reported to be effective for the prevention of recurrent CDI. In addition, approaches to restoring the gut microbiota by using probioitcs and live biotherapeutic products (LBPs) are currently being studied to examine the effect on CDI. Further microbial ecological research on C. difficile and gut microbiota could lead to a better understanding of the pathogenesis and treatment of CDI.

Obesity-induced inflammation plays a substantial role in the development of insulin resistance and type 2 diabetes. The altered gut flora in obesity can also contribute to metabolic dysregulation and systemic inflammation. However, it remains unclear how dysregulation of systemic inflammation in obesity affects the gut microbiome. We hypothesized that colchicine’s systemic anti-inflammatory effects in obesity would be associated with improvements in gut microbial diversity. We conducted a secondary analysis of a double-blind randomized placebo-controlled trial, in which 40 adults with obesity, high CRP (≥2.0 mg/L), insulin resistance (HOMA-IR ≥2.6 mg/L), and metabolic syndrome (MetS) were randomized to three months of colchicine 0.6 mg or placebo tablets twice daily. Serum and stool samples were collected at baseline and final visit. Gut microbiota composition was characterized from stool DNA by dual-index amplification and sequencing of 16S ribosomal RNA. Pre- and post-intervention stool samples were available for 15 colchicine- and 12 placebo-treated subjects. Circulating hsCRP, interleukin-6, resistin, white blood count, and neutrophils were significantly decreased in the colchicine arm as compared to placebo. However, changes in stool microbiome alpha diversity, as assessed by the Chao1, Shannon, and Pielou indices, were not significant between groups. Amplicon sequence variant counts were unchanged among all examined phyla or families. Oscillibacter was the only genus to demonstrate even a nominally significant change. Among adults with obesity and MetS, colchicine significantly improved systemic inflammation. However, this anti-inflammatory effect was not associated with significant changes in the gut microbiome. Further studies are warranted to investigate this relationship.

MicroRNAs (miRNAs) are small non-coding RNA species involved in diverse physiological processes, including immunity. Accumulating evidence suggests that miRNA-induced gene silencing plays a significant role in the regulation of the intestinal immune system by the gut commensal microbiota. This review aims to provide an overview of the intestinal miRNA-mediated crosstalk between the gut microbiota and the host intestinal immune system. First, we describe the role of miRNAs in regulating the intestinal immune system. Then we describe the effect of the gut microbiota on intestinal miRNA expression. Subsequently, we describe the role of miRNAs in the modulation of the intestinal immune system by the gut microbiota. Finally, we describe the effect of host miRNAs on the gut microbiota. Although the entire picture of this complex crosstalk remains unclear, efforts to unravel it will contribute significantly to developing new strategies for preventing and treating intestinal immune disorders such as inflammatory bowel disease.

The role of the composition of the gut microbiota on human health is not well understood. However, during the past decade, an increased emphasis has been placed on the influence of the impact of nutrition on the composition of gut microbiota and how the gut microbiota affects human health. The current review focuses on the role of some of the most studied phytochemicals on the composition of the gut microbiota. First, the review highlights the state of the research evidence regarding dietary phytochemical consumption and gut microbiota composition, including the influence of phytochemicals such as polyphenols, glucosinolates, flavonoids, and sterols that are present in vegetables, nuts, beans, and other foods. Second, the review identifies changes in health outcomes with altered gut microbiota composition, in both animal and human model studies. Third, the review highlights research that includes both associations between dietary phytochemical consumption and gut microbiota composition, and associations between the gut microbiota composition and health outcomes, in order to elucidate the role of the gut microbiota in the relationship between dietary phytochemical consumption and health outcomes in humans and animals. The current review indicated that phytochemicals can beneficially alter gut microbiota composition and decrease the risk for some diseases, such as cancers, and improve some cardiovascular and metabolic risk biomarkers. There is an urgent demand for high-quality studies that determine the relationships between the consumption of phytochemicals and health outcomes, examining gut microbiota as a moderator or mediator.

The human microbiota-gut-brain axis has an enormous role in the maintenance of homeostasis and health. Over the last two decades, it has received concerted research attention and focus due to a rapidly emerging volume of evidence that has established that impairment within the microbiota-gut-brain axis contributes to the development and progression of various diseases. Stroke is one of the entities identified to be associated with microbiota-gut-brain axis impairment. Currently, there are still limitations in the clinical treatment of stroke, and the presence of a non-nervous factor from gut microbiota that can alter the course of stroke presents a novel strategy towards the search for a therapeutic silver bullet against stroke. Hence, the aim herein, was to focus on the involvement of microbiota-gut-brain axis impairment in the pathogenesis stroke as well as elucidate its implications as a potent therapeutic target against stroke. The findings of studies to date have revealed and extended the role microbiota-gut-brain axis impairment in the pathogenesis of stroke, and studies have identified from both clinical and pre-clinical perspectives targets within the microbiota-gut-brain axis and successfully modulated the outcome of stroke. It was concluded that the microbiota-gut-brain axis stands as potent target to salvage the neurons in the ischemic penumbra for the treatment of stroke. Assessment of the microbiota profile and its metabolites status holds enormous clinical potentials as a non-invasive indicator for the early diagnosis and prognosis of stroke.

A placebo-controlled, randomized, double-blind study was conducted to evaluate the effect of taking 25 billion colony-forming units of heat-killed Bifidobacterium longum CLA8013 over 2 weeks on bowel movements in constipation-prone healthy individuals. The primary endpoint was the change in defecation frequency between the baseline and 2 weeks after the intake of B. longum CLA8013. The secondary endpoints were the number of days of defecation, stool volume, stool consistency, straining during defecation, pain during defecation, feeling of incomplete evacuation after defecation, abdominal bloating, fecal water content, and the Japanese version of the Patient Assessment of Constipation Quality of Life. A total of 120 individuals were assigned to two groups, 104 (control group, n=51; treatment group, n=53) of whom were included in the analysis. After 2 weeks of consuming the heat-killed B. longum CLA8013, defecation frequency increased significantly in the treatment group compared with that in the control group. Furthermore, compared with the control group, the treatment group showed a significant increase in stool volume and significant improvement in stool consistency, straining during defecation, and pain during defecation. No adverse events attributable to the heat-killed B. longum CLA8013 were observed during the study period. This study revealed that heat-killed B. longum CLA8013 improved the bowel movements of constipation-prone healthy individuals and confirmed that there were no relevant safety issues.

Maternal environments affect the health of offspring in later life. Changes in epigenetic modifications may partially explain this phenomenon. The gut microbiota is a critical environmental factor that influences epigenetic modifications of host immune cells and the development of food allergies. However, whether changes in the maternal gut microbiota affect the development of food allergies and related epigenetic modifications in subsequent generations remains unclear. Here, we investigated the effects of antibiotic treatment before pregnancy on the development of the gut microbiota, food allergies, and epigenetic modifications in F1 and F2 mice. We found that pre-conception antibiotic treatment affected the gut microbiota composition in F1 but not F2 offspring. F1 mice born to antibiotic-treated mothers had a lower proportion of butyric acid-producing bacteria and, consequently, a lower butyric acid concentration in their cecal contents. The methylation level in the DNA of intestinal lamina propria lymphocytes, food allergy susceptibility, and production of antigen-specific IgE in the F1 and F2 mice were not different between those born to control and antibiotic-treated mothers. In addition, F1 mice born to antibiotic-treated mothers showed increased fecal excretion related to the stress response in a novel environment. These results suggest that the maternal gut microbiota is effectively passed onto F1 offspring but has little effect on food allergy susceptibility or DNA methylation levels in offspring.

Pellagra is caused by abnormal intake and/or use of nicotinic acid and is known in part to be induced by the use of medications such as isoniazid or pirfenidone. We previously investigated atypical phenotypes of pellagra, such as nausea, using a mouse model of pellagra and found that gut microbiota play an important role in the development of these phenotypes. Here, we investigated the effect of Bifidobacterium longum BB536 on pellagra-related nausea caused by pirfenidone in our mouse model. Our pharmacological data indicated that pirfenidone (PFD) causes modulation of the gut microbiota profile, which appeared to play an important role in the development of pellagra-related nausea. A gut microbiota-mediated protective effect of Bifidobacterium longum BB536 against nausea caused by PFD was also identified. Finally, the urinary ratio of nicotinamide/N-methylnicotinamide was shown to be a biomarker of pellagra-like adverse effects induced by PFD, and it may contribute to the prevention of these effects in patients with idiopathic pulmonary fibrosis.

Previous studies suggested that altered gut serotonin (5-HT) signaling is implicated in the pathophysiology of inflammatory bowel disease (IBD). Indeed, 5-HT administration reportedly exacerbated the severity of murine dextran sodium sulfate (DSS)-induced colitis that mimics human IBD. Our recent study suggested that Bifidobacterium pseudolongum, one of the most predominant bifidobacterial species in various mammals, reduces the colonic 5-HT content in mice. The present study thus tested whether the administration of B. pseudolongum prevents DSS-induced colitis in mice. Colitis was induced by administering 3% DSS in drinking water in female BALB/c mice, and B. pseudolongum (10⁹ CFU/day) or 5-aminosalicylic acid (5-ASA, 200 mg/kg body weight) was intragastrically administered once daily throughout the experimental period. B. pseudolongum administration reduced body weight loss, diarrhea, fecal bleeding, colon shortening, spleen enlargement, and colon tissue damage and increased colonic mRNA levels of cytokine genes (Il1b, Il6, Il10, and Tnf) almost to an extent similar to 5-ASA administration in DSS-treated mice. B. pseudolongum administration also reduced the increase of colonic 5-HT content, whereas it did not alter the colonic mRNA levels of genes that encode the 5-HT synthesizing enzyme, 5-HT reuptake transporter, 5-HT metabolizing enzyme, and tight junction-associated proteins. We propose that B. pseudolongum is as beneficial against murine DSS-induced colitis as the widely used anti-inflammatory agent 5-ASA. However, further studies are needed to clarify the causal relationship between the reduced colonic 5-HT content and reduced severity of DSS-induced colitis caused by B. pseudolongum administration.

Turmeronols (A and B), bisabolane-type sesquiterpenoids found in turmeric, reduce inflammation outside the brain in animals; however, their effects on neuroinflammation, a common pathology of various neurodegenerative diseases, are not understood. Inflammatory mediators produced by microglial cells play a key role in neuroinflammation, so this study evaluated the anti-inflammatory effects of turmeronols in BV-2 microglial cells stimulated with lipopolysaccharide (LPS). Pretreatment with turmeronol A or B significantly inhibited LPS-induced nitric oxide (NO) production; mRNA expression of inducible NO synthase; production of interleukin (IL)-1β, IL-6, and tumor necrosis factor α and upregulation of their mRNA expression; phosphorylation of nuclear factor-κB (NF-κB) p65 proteins and inhibitor of NF-κB kinase (IKK); and nuclear translocation of NF-κB. These results suggest that these turmeronols may prevent the production of inflammatory mediators by inhibiting the IKK/NF-κB signaling pathway in activated microglial cells and can potentially treat neuroinflammation associated with microglial activation.

Enterococcus faecium 129 BIO 3B is a lactic acid bacterium that has been safely used as a probiotic product for over 100 years. Recently, concerns about its safety have arisen because some species of E. faecium belong to the vancomycin-resistant enterococci. The groups of E. faecium with less pathogenic potential have been split into a separate species (Enterococcus lactis). In this study, I investigated the phylogenetic classification and safety of E. faecium 129 BIO 3B as well as E. faecium 129 BIO 3B-R, which is naturally resistant to ampicillin. Mass spectrometry and basic local alignment search tool analysis using specific gene regions failed to differentiate 3B and 3B-R into E. faecium or E. lactis. However, multilocus sequence typing successfully identified 3B and 3B-R as the same sequence types as E. lactis. Overall genome relatedness indices showed that 3B and 3B-R have high degrees of homology with E. lactis. Gene amplification was confirmed for 3B and 3B-R with E. lactis species-specific primers. The minimum inhibitory concentration of ampicillin was confirmed to be 2 µg/mL for 3B, which is within the safety standard for E. faecium set by the European Food Safety Authority. Based on the above results, E. faecium 129 BIO 3B and E. faecium 129 BIO 3B-R were classified as E. lactis. The absence of pathogenic genes except for fms21 in this study demonstrates that these bacteria are safe for use as probiotics.