Why patients with symptomatic uncomplicated diverticular disease (SUDD) may develop acute diverticulitis (AD) is still unknown. We analyzed the gut microbiota (GM) in two SUDD patients, one who did experience SUDD recurrence but not AD occurrence (case 1) and one who did experience AD occurrence during follow-up (case 2). The GM of these patients showed differences in terms of phyla (Firmicutes and Bacteroidota in case 1; Actinobacteriota and Proteobacteria in case 2) and subgenera (Prevotella and Phascolarctobacterium in case 1 and Alloprevotella, Prevotella, Holdemanella, Turicibacter, Eubacterium eligens group, and Dialister in case 2). This novel insight may advance our ecological understanding of this complex disease.

The global probiotics market has been continuously growing, driven by consumer demand for immune-enhancing functional foods, dietary supplements, and natural therapeutics for gastrointestinal and gut function-mediated diseases. Probiotic microorganisms represent a diverse group of strains with complex but generalized mechanistic patterns. This review describes the various immunomodulatory mechanisms by which probiotics exert their effects, including the competitive exclusion of pathogenic microbes, production of antimicrobial substances, modulation of the immune system, and improvement of gut barrier function. In addition, the various formulations and methods of delivery of probiotics and the safety concerns associated with these products are also discussed.

Vitiligo is a prevalent acquired depigmenting disease that is distinguished by the depletion of functional melanocytes and epidermal melanin. Despite significant advancements in comprehending vitiligo, the precise etiology and pathogenesis of the condition remain elusive. So far, the treatment of vitiligo is still one of the most difficult dermatological challenges. Thus, developing a better understanding of vitiligo pathogenesis to develop more effective treatments is very important. Vitiligo has long been acknowledged as an autoimmune disorder, and microbes serve as crucial regulators of the immune system, exerting influences on diverse autoimmune diseases. Numerous studies have revealed the involvement of microorganisms, including bacteria and viruses, in the progression of vitiligo. This review provides a concise overview of the correlation between microbes and vitiligo, while also elucidating the potential mechanisms by which microbes may influence the development of vitiligo. The ultimate objective is to offer a comprehensive understanding of the prospects for vitiligo treatment.

In end-stage kidney disease requiring hemodialysis, patients at nutritional risk have a poor prognosis. The gut microbiota is important for maintaining the nutritional status of patients. However, it remains unclear whether an altered gut microbiota correlates with increased nutritional risk in patients undergoing hemodialysis. Therefore, we retrospectively analyzed patients who underwent hemodialysis at our hospital between April and December 2022. Nutritional risk was evaluated using the Geriatric Nutritional Risk Index (GNRI), and patients were divided into low- and high-GNRI groups. Patients’ clinical conditions and alterations in the gut microbiota were compared between the two groups. The study included a total of 38 patients with moderate to severe frailty. The low-GNRI group had 18 patients, and the high-GNRI group had 20 patients. The low-GNRI group had more severely frail patients. Serum transthyretin, cholinesterase, total cholesterol, and β2-microglobulin were significantly lower in the low-GNRI group than in the high-GNRI group. Significant differences in the relative abundances of the Actinobacteria and Proteobacteria phyla were observed between the two groups. The genus Bifidobacterium was significantly less abundant in the high-GNRI group than in the low-GNRI group. At the species level, Bifidobacterium adolescentis and Bifidobacterium bifidum were significantly lower in the low-GNRI group. Our results indicated that GNRI can be a useful nutritional risk index that accurately reflects the comprehensive differences in clinical condition in patients undergoing hemodialysis. The deficiency of B. adolescentis and B. bifidum was strongly associated with an increased nutritional risk in patients undergoing hemodialysis.

Beer contains a variety of bioactive ingredients and trace elements that can regulate bodily functions, and moderate consumption of beer can enhance immune responses. This study aimed to investigate the potential benefits of moderate consumption of alcoholic or non-alcoholic beer on the gut microbiome, immunity, and intestinal barrier function in immunosuppressed BALB/c mice induced by cyclophosphamide (CTX). Model mice with CTX-induced immunosuppression were administered alcoholic or non-alcoholic beer or galacto-oligosaccharides (GOS) for 28 consecutive days. The GOS and beer intervention groups all showed alleviation of spleen tissue damage, an increased immune organ index, decreased gut inflammation, and reduced serum concentrations of D-lactic acid, lipopolysaccharide, and tumor necrosis factor α. High-throughput 16S rRNA gene sequencing revealed higher relative abundances of Firmicutes and Actinobacteriota, and lower relative abundances of Bacteroidota, Lactobacillus, and Bifidobacterium, in CTX mice than in normal control mice. In addition, Firmicutes showed lower abundance, while Desulfobacterota showed higher abundance in CTX mice with non-alcoholic beer intake than without it. Spearman correlation analysis indicated that Bacteroidota was negatively correlated with propionic acid and butyric acid, while Desulfobacterota was positively correlated with butyric acid. Proteobacteria was negatively correlated with acetic acid, propionic acid, isobutyric acid, and valeric acid. Helicobacter was positively correlated with valeric acid. In conclusion, this is one of the first studies to examine the modulatory effects of moderate alcohol consumption in immunocompromised mice. Our findings indicate that beer consumption can alter the gut microbiome and metabolites, enhancing immunity in mice.

Phagocytosis by immunocompetent cells is a key role in the biological defense mechanism and is the starting point of the reaction that leads from innate to acquired immunity. Several studies have demonstrated that some lactic acid bacteria strains activate the innate and acquired immune systems of the host. However, further investigation of the mechanism and improvement of usefulness is needed because the effect differs depending on the type and strain of lactic acid bacteria. In this study, we focused on the phagocytosis to lactic acid bacteria and investigated changes in phagocytic activity in vitro using several species of lactic acid bacteria and α-lipoic acid, which was expected to enhance phagocytosis. As a result, we found that α-lipoic acid treatment increased phagocytosis in several lactic acid bacteria. Strains of lactic acid bacteria with increased phagocytosis were found to have decreased CD36 expression when lactic acid bacteria alone were used, and CD36 expression was restored when α-lipoic acid was used in combination, indicating a correlation between increased phagocytosis and CD36 expression. Furthermore, the combination of Lactococcus lactis subsp. hordniae NBRC 100931 and α-lipoic acid increased phagocytosis over time and enhanced IgA production. These results suggest that the combination of α-lipoic acid and lactic acid bacteria increases the phagocytosis capacity of immunocompetent cells and may enhance the immunostimulatory effects of lactic acid bacteria.

The beneficial effects of water-soluble dietary fiber on liver fat and fibrosis involve the gut microbiota; however, few epidemiological studies have investigated this association. This large-scale epidemiological study aimed to determine the effect of water-soluble dietary fiber intake on liver fat and fibrosis via gut microbiota for the general population. We divided low- and high-intake groups by median daily water-soluble dietary fiber intake and matched background factors by propensity score matching for sex and age. The high-intake group had lower controlled attenuation parameters, a lower fatty liver index, and a lower mac-2-binding protein glycosylated isomer level than the low-intake group. Furthermore, in the high-intake group, the prevalences of metabolic dysfunction-associated steatotic liver disease and cardiometabolic criteria were significantly lower than in the low-intake group. In the high-intake group, there were increases and decreases in 16 bacterial species. Of them, those belonging to Faecalibacterium and Gemmiger had higher relative abundances than the other species and had a negative correlation with the fatty liver index and its components triglyceride and glutamyl transpeptidase in a multivariate analysis adjusted for confounding factors. On the other hand, Dorea showed a significant negative correlation with liver stiffness measure, even though Dorea was decreased in the high-intake group. Faecalibacterium and Gemmiger are butyrate-producing bacteria, suggesting that water-soluble dietary fiber may inhibit fatty liver via gut butyric acid production.

Probiotics exert their beneficial effects by improving the intestinal environment. Heat-inactivated probiotics may show similar effects. However, whether multi-strain mixtures (MSM) are better than single strains, irrespective of whether the bacteria are alive or dead, is unknown. In this study, we examined the gut-improving efficacy of an MSM consisting of four dead bacterial strains using an in vitro model that simulates the human gut environment. In the in vitro model, human feces were inoculated with a single-strain or MSM, and the microbial composition and fermentation products were assessed. The 16S rRNA gene sequences showed that the MSM tended to change the microbial community structure more than single strains. Furthermore, the results of a microbial diversity analysis showed that despite differences among single strains, the effect of the MSM increased with the abundance of any single strain. A similar trend was observed for fermentation products. These results suggested that the MSM made from dead bacteria exerted additive effects that may provide new health benefits to more people.

Although the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system has been extensively developed since its discovery for eukaryotic and prokaryotic genome editing and other genetic manipulations, there are still areas warranting improvement, especially regarding bacteria. In this study, BRD0539, a small-molecule inhibitor of Streptococcus pyogenes Cas9 (SpCas9), was used to suppress the activity of the nuclease during genetic modification of Lacticaseibacillus paracasei, as well as to regulate CRISPR interference (CRISPRi). First, we developed and validated a CRISPR-SpCas9 system targeting the sirA gene of L. paracasei. Then BRD0539 was used for CRISPR-dependent DNA cleavage in vivo. Our results suggested that the inhibitor worked partially in both Escherichia coli and L. paracasei. Next, we designed a CRISPRi system in a L. paracasei strain by inserting an inactive SpCas9 gene into the chromosome and introducing a plasmid encoding for a single guide RNA (sgRNA) targeting the sirA gene. Expression of sirA was successfully inhibited in the recombinant strains, and CRISPRi was abolished in an inhibitor-dependent manner. Our findings may help expand the CRISPR toolbox for research on lactic acid bacteria and other microbes.

α-Cyclodextrin (αCD), a cyclic hexasaccharide composed of six glucose units, is not digested in the small intestine but is completely fermented by gut microbes. Recently, we have reported that αCD supplementation for nonathlete men improved their 10 km biking times. However, the beneficial effects of αCD on exercise are not yet fully understood. Therefore, we conducted a randomized, double-blind, placebo-controlled, parallel-group study to confirm the reproducibility and obtain additional data, employing a larger sample size and a greater αCD dose than that used in our previous study. Age, body mass index, estimated V̇O₂ max, and Bacteroides uniformis cell number in feces were used as stratifying factors. Eighty-one healthy nonathlete men aged 20 to 49 years who had exercise habits received a placebo (n=42) or αCD (1 g/day; n=39) for 9 weeks. Similar to our previous study, αCD supplementation significantly improved endurance exercise performance (10 km biking time trial) compared with the placebo (placebo=1,126.4 ± 133.6 s, αCD=1,073.2 ± 116.7 s, p=0.016). In addition, we observed a significantly reduced visual analog scale score for post-exercise fatigue (placebo=59.0 [46.3–54.3] mm, αCD=48.8 [37.0–50.3] mm, p=0.043). The heart rate increase was lower in the αCD group than in the placebo group during exercise (placebo=152.3 ± 11.1 bpm, αCD=144.2 ± 16.3 bpm, p=0.016). These results indicate that αCD supplementation improves endurance exercise performance and reduces post-exercise fatigue in nonathlete men.

Airag, a fermented mare’s milk in Mongolia, exhibits diverse flavors and microbiota due to distinct production processes and environments in nomadic households. Recently, there has been a shift from the traditional cow skin container, ‘khokhuur’, to a plastic container for airag production, potentially impacting the microbiota and quality. To address this notion, we aimed to elucidate the differences in the microbiota between airag samples from a plastic container and those from a khokhuur. We collected airag samples produced using either a plastic container or khokhuur from three houses in Mogod Sum (county) in Bulgan Aimag (province) and analyzed the chemical and microbiome properties of the obtained samples. Compared with the khokhuur, the plastic containers exhibited high heat retention at night and boosted lactate production, which sustained a lower pH level in airag. A series of alpha diversity indices of airag microbiota were significantly higher in airag produced in khokhuurs than in those produced in the plastic containers. In particular, Lactobacillus helveticus was the most dominant species, accounting for more than 90% of the total population in airags produced in the plastic containers and khokhuur, whereas some other lactic acid bacteria species and environmental bacteria more colonized airags produced in khokhuurs. The khokhuur itself is likely a source of these bacterial species and likely provides a niche, and the wider volatility of temperature may allow the growth of this wide range of bacteria while maintaining a lower level of lactic acid fermentation.