Single-strain species are commonly used as probiotics with low birth weight neonates. However, the effectiveness and safety of multi-strain supplementation are not well known. Thirty-six neonates weighing less than 2,000 g (558-1,943 g) at birth and admitted to a neonatal intensive care unit were randomly assigned to receive a single strain or triple strains of with lactulose enterally for 4 weeks from birth. The relative abundances of and in the fecal microbiota at weeks 1, 2, and 4 were investigated. Based on the study results, no significant difference was detected between the two groups in the abundance of ; however, the triple-strain group had significantly high abundances of at weeks 2 and 4. The fecal microbiota in the triple-strain group had significantly lower alpha diversity (-enriching) after week 4 and was different from that in the single-strain group, which showed a higher abundance of No severe adverse events occurred in either group during the study period. Although no significant difference was detected between single- and multi-strain bifidobacteria supplementation in the colonization of in the fecal microbiota of the neonates, multi-strain bifidobacteria supplementation contributed toward early enrichment of the microbiota with bifidobacteria and suppression of other pathogenic bacteria, such as spp.

This research aimed to examine the effect of daily intake of food containing strain T21 (T21) on skin conditions and inflammation-related markers in healthy adults who experience itching because of dry skin and have an atopic predisposition. A randomized, double-blind, placebo-controlled parallel-group study was conducted on 44 subjects aged 20 to 64 years. Subjects were randomly assigned to receive a T21-containing food or placebo daily for 8 weeks. The hydration of stratum corneum, trans-epidermal water loss, skin brightness (*), skin redness (*), and quality of life (QOL) scores were evaluated. Moreover, SCCA2, Th1/Th2, peripheral blood eosinophil count, TGF-β1, TARC, total IgE, and LDH were measured as inflammation-related markers. The results showed that, compared with the placebo, food containing T21 reduced trans-epidermal water loss in the neck and increased neck skin brightness (*) after 8 weeks of consumption. Furthermore, a stratified analysis in subjects with a history of atopy showed improvements in neck skin redness (*) and skin-related QOL. No significant improvement in inflammation-related markers was observed. Intake of food containing T21 for 8 weeks in healthy adult with atopic predisposition was suggested to improve skin barrier function in the neck and brightness in the neck skin. Furthermore, the results also suggested that it had the effect of improving rough skin and reducing discomfort due to dryness in healthy adults with a history of atopy.

Emerging research indicates the potential involvement of gut bacteria in the etiology of Graves' Disease (GD). However, the evidence regarding this matter is still conflicting. The primary objective of this investigation was to examine the correlation between gut microbiota and GD. A comprehensive search was conducted of the Cochrane Library, Scopus, Europe PMC, and Medline databases up until August 1, 2023, utilizing a combination of relevant keywords. This review incorporates literature that examined the composition of gut microbiota in patients with GD. We employed random-effect models to analyze the standardized mean difference (SMD) and present the outcomes together with their corresponding 95% confidence intervals (CIs). A total of ten studies were incorporated. The results of our meta-analysis indicated that patients with GD have a reduced alpha diversity of gut microbiota as evidence by a significant reduction of Chao1 (std. mean difference -0.58; 95% CI -0.90, -0.26, p=0.0004; =61%), ACE (std. mean difference -0.64; 95% CI -1.09, -0.18, p=0.006; =77%), and Shannon index (std. mean difference -0.71; 95% CI -1.25, -0.17, p=0.01; =90%) when compared with healthy controls. At the phylum level, the abundance of Firmicutes was reduced in GD patients, while that of Bacteroidetes was increased. This study suggests a notable decrease in the richness and variety of gut microbiota among people diagnosed with GD in comparison with healthy controls.

Diverse bacterial and fungal microbiota communities inhabit the human body, and their presence is essential for maintaining host homeostasis. The oral cavity, lung, gut, and vagina are just a few of the bodily cavities where these microorganisms communicate with one another, either directly or indirectly. The effects of this interaction can be either useful or detrimental to the host. When the healthy microbial diversity is disturbed, for instance, as a result of prolonged treatment with broad spectrum antibiotics, this allows the growth of specific microbes at the expense of others and alters their pathogenicity, causing a switch of commensal germs into pathogenic germs, which could promote tissue invasion and damage, as occurs in immunocompromised patients. Consequently, antimicrobials that specifically target pathogens may help in minimizing secondary issues that result from the disruption of useful bacterial/fungal interactions (BFIs). The interface between and with bacteria at various body sites is emphasized in the majority of the medically important BFIs that have been reported thus far. This interface either supports or inhibits growth, or it enhances or blocks the generation of virulence factors. The aim of this review is to draw attention to the link between the bacterial and fungal microbiota and how they contribute to both normal homeostasis and disease development. Additionally, recent research that has studied microbiota as novel antimicrobials is summarized.

Probiotics such as bifidobacteria have been given to low-birth-weight neonates (LBWNs) at risk for a disrupted gut microbiota leading to the development of serious diseases such necrotizing enterocolitis. Recently prebiotics such as lactulose are used together with bifidobacteria as synbiotics. However, faster and more powerful bifidobacteria growth is desired for better LBWN outcomes. The prebiotic 1-kestose has a higher selective growth-promoting effect on bifidobacteria and lactic acid bacteria among several oligosaccharides. Twenty-six premature neonates (less than 2,000 g) admitted to a neonatal intensive care unit (NICU) were randomly assigned to receive M16-V with either 1-kestose or lactulose once a day for four weeks from birth. A 16S rRNA gene analysis revealed similar increases in alpha-diversity from 7 to 28 days in both groups. The most dominant genus on both days was in both groups, with no significant difference between the two groups. Quantitative PCR analysis revealed that the number of tended to be lower in the 1-kestose group than in the lactulose group at 28 days. The number of was higher in the 1-kestose group at 7 days. The copy number of total bacteria in the 1-kestose group was significantly higher than that in the lactulose group at 3 time points, 7, 14, and 28 days. No severe adverse events occurred in either group during the study period. l-Ketose may offer an alternative option to lactulose as a prebiotic to promote the development of gut microbiota in LBWNs.

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 V̇O max, and 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.

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 and 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, showed a significant negative correlation with liver stiffness measure, even though was decreased in the high-intake group. and are butyrate-producing bacteria, suggesting that water-soluble dietary fiber may inhibit fatty liver via gut butyric acid production.

Nukadoko, a fermented rice bran bed for pickling vegetables called nukazuke, has a complex microbiota. Within it, deep interactions between the microbiota of the pickled vegetables and nukadoko characterize and control the qualities of both products. To address this notion, we monitored the changes in the microbiota of nukadoko and nukazuke while pickling different vegetables. Raw or roasted rice bran was mixed with salted water and fermented at 24°C for 40 days, following which different species of vegetable, var. , var. or var. were pickled. The microbial composition of the washing solution of fresh vegetables, as well as that of the nukadoko and nukazuke for each vegetable, was analyzed by amplicon sequencing of 16S rRNA genes. Although the microbiota of nukadoko varied depending on the species of pickled vegetables, no transcolonization of any species of bacteria from fresh vegetables to nukadoko was observed. However, some lactic acid bacterium (LAB) species eventually dominated the microbiota of both nukazuke and matured nukadoko, although they were not detected in either the fresh vegetables or rice bran. Particularly, was dominant among all pairs of pickled vegetables and matured nukadoko, whereas the transcolonization of some other LAB species was observed in a pickled vegetable-specific manner. was observed to some extent in each nukadoko, yet it was not detected in any nukazuke. Overall, a LAB-dominant microbiota was established in both nukadoko and nukazuke in an underlying process that was different but partly common among vegetables.

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.

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, 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.

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 model that simulates the human gut environment. In the 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.

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 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 subsp. 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.

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 was significantly less abundant in the high-GNRI group than in the low-GNRI group. At the species level, and 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 and was strongly associated with an increased nutritional risk in patients undergoing hemodialysis.

Pulmonary fibrosis is an end-stage respiratory disease characterized by fibroblast proliferation and accumulation of extracellular matrix and collagen, which is accompanied by inflammatory damage. The disease is mainly based on pulmonary dysfunction and respiratory failure, the incidence of it is increasing year by year, and the current treatment methods for it are limited. In recent years, it has been found that gut microbes play a crucial role in the pathogenesis and development of pulmonary fibrosis. The microecological disturbance caused by changes in the composition of the intestinal flora can affect the course of pulmonary fibrosis. The regulatory network or information exchange system for gut-lung crosstalk is called the "gut-lung axis". This review focuses on the frontier research on entero-pulmonary regulation in pulmonary fibrosis and on intervention strategies for changing the gut microbiota to improve pulmonary fibrosis, including fecal microbiota transplantation, traditional Chinese medicine interventions, and supplementation with probiotics. In addition, the present problems in this field are also raised in order to provide strong theoretical and strategic support for the future exploration of regulatory mechanisms and therapeutic drug development. This paper reviews the interaction of the intestinal flora with pulmonary fibrosis, introduces the research progress for improving pulmonary fibrosis through interventions targeted at the intestinal flora, and provides new ideas for the treatment of pulmonary fibrosis.

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, , and , 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. 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.

Intestinal homeostasis and integrity are important factors for maintaining host health. This study established intestinal epithelial cell lines and organoids from the same swine jejunal crypts to develop seamless swine intestinal evaluation systems. The study evaluated the proliferative capacity and tight junction formation of the epithelial cell line and characterized the cell differentiation potential of the intestinal organoids. The evaluation systems were subsequently exposed to the Toll-like receptor 3 (TLR3) agonist poly(I:C) to simulate viral infections and assess the antiviral responses. The results demonstrated no differences in the response to type I interferons. There were, however, significant differences in the expression of interferon-stimulated genes. This study collectively introduced a flexible evaluation system using cell lines and organoids and revealed notable differences in the expression of interferon-stimulated genes, highlighting the complexity of the immune responses in these systems and the importance of intestinal heterogeneity in assessing viral responses.

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 ( and in case 1 and , , , , group, and in case 2). This novel insight may advance our ecological understanding of this complex disease.

Depression is a prevalent mental health disorder, and its incidence has increased further because of the coronavirus disease 2019 (COVID-19) pandemic. The gut microbiome has been suggested as a potential target for mental health treatment because of the bidirectional communication system between the brain and gastrointestinal tract, known as the gut-brain axis. We aimed to investigate the relationship between the human gut microbiome and depression screening by analyzing the abundance and types of microbiomes among individuals living in Japan, where mental health awareness and support may differ from those in other countries owing to cultural factors. We used a data-driven approach to evaluate the gut microbiome of participants who underwent commercial gut microbiota testing services and completed a questionnaire survey that included a test for scoring depressive tendencies. Our data analysis results indicated that no significant differences in gut microbiome composition were found among the groups based on their depression screening scores. However, the results also indicated the potential existence of a few differentially abundant bacterial taxa. Specifically, the detected bacterial changes in abundance suggest that the Bifidobacteriaceae, Streptococcaceae, and Veillonellaceae families are candidates for differentially abundant bacteria. Our findings should contribute to the growing body of research on the relationship between gut microbiome and mental health, highlighting the potential of microbiome-based interventions for depression treatment. The limitations of this study include the lack of clear medical information on the participants' diagnoses. Future research could benefit from a larger sample size and more detailed clinical information.

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 Japan, the growing interest in anti-aging skin care is associated with the unprecedented aging society. Skin aging can be attributed to various factors, including the activation of hyaluronidase enzyme in subcutaneous tissues exposed to ultraviolet radiation. This enzyme breaks down hyaluronic acid, leading to skin sagging. Therefore, hyaluronidase inhibitors can effectively prevent skin aging. Previously, food components have been actively explored to search for hyaluronidase inhibitors considering the high safety of these materials. Although lactic acid bacteria (LAB)-fermented foods inhibit this enzyme, their active compounds responsible for hyaluronidase inhibition remain unknown. Thus, in this study, we aimed to explore the mechanism underlying the LAB-mediated inhibition of hyaluronidase activity. Supernatants of a LAB-fermented milk-based beverage were subjected to a hyaluronidase inhibition assay, followed by purification and separation using hydrophobic adsorbents and high-performance liquid chromatography, respectively. Subsequently, liquid chromatograph time-of-flight mass analysis was performed, revealing α-ketoglutarate (AKG) as the inhibitor of this enzyme. The half-maximal inhibitory concentration (IC) of AKG was approximately 0.13-fold that of the known strong hyaluronidase inhibitor disodium cromoglycate (DSCG). To the best of our knowledge, this is the first report on hyaluronidase inhibition mediated by AKG, a metabolic product of LAB. Additionally, JCM1132 was identified as a highly effective AKG-producing LAB (63.9 µg/mL) through LC-MS/MS-based quantitative analyses using various LAB-fermented milk samples. We anticipate that the findings of this study will potentially support the development of functional foods and cosmetics enriched with AKG.

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 Cas9 (SpCas9), was used to suppress the activity of the nuclease during genetic modification of , as well as to regulate CRISPR interference (CRISPRi). First, we developed and validated a CRISPR-SpCas9 system targeting the gene of . Then BRD0539 was used for CRISPR-dependent DNA cleavage . Our results suggested that the inhibitor worked partially in both and . Next, we designed a CRISPRi system in a strain by inserting an inactive SpCas9 gene into the chromosome and introducing a plasmid encoding for a single guide RNA (sgRNA) targeting the gene. Expression of 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.