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The decline in ovarian estrogen production is known to have detrimental health consequences and negatively affect the quality of life in menopausal women. Increasing estradiol levels is key to preventing disease in menopausal women. In this study, Lactobacillus gasseri CCFM1255 isolated from healthy infants was found to have a positive effect on estradiol production in ovariectomized rats. CYP19, the key enzyme catalysing the conversion of androgens into estrogens, was upregulated in adipose tissue upon CCFM1255 treatment. Untargeted metabolome analysis and targeted metabolite detection were used to identify the key metabolites altered by CCFM1255 treatment. CCFM1255 treatment significantly improved the serum concentration of glutamine (Gln). A significantly positive correlation was observed between serum Gln and estradiol concentrations. CCFM1255 treatment reshaped the structure of the gut microbiome, which was correlated with certain changes in serum metabolite concentrations. These results indicate that the provision of CCFM1255 as a dietary supplement may be an effective strategy to alleviate menopausal symptoms by increasing circulating estradiol.

Lactobacillus spp. can be beneficial for the prevention or treatment of ulcerative colitis (UC). In this study, 153 participants who followed vegan, omnivorous, or high-meat diet were recruited. Compositional analysis of the Lactobacillus community in feces revealed that Lactobacillus fermentum strains were significantly affected by diet. Administration of mixed L. fermentum strains from vegans significantly improved inflammation compared to that from omnivores and high-meat consumers, as evidenced by a significant reduction in colonic tissue damage, improvement in inflammatory cytokines, enhanced expression of ZO-1, occludin, and claudin-3, and a significant increase in short chain fatty acids concentration. The effect of a single strain of L. fermentum was similar to that of a mixed strains of L. fermentum group. Genomic analysis suggested that L. fermentum strains from the guts of vegans possessed a higher prevalence of genes involved in carbohydrate catabolism than those from the guts of omnivores and high-meat eaters. In particular, the ME2 gene is involved in the biosynthesis of acetate, a compound considered to possess anti-inflammatory properties. In conclusion, this study indicates strain-specific differences in the ability of L. fermentum strains to alleviate UC in mice, influenced by habitual diets.

This study aimed to evaluate the effects of Bifidobacterium breve CCFM683 on psoriasis and to investigate the underlying mechanisms. B. breve CCFM683 significantly ameliorated psoriasis in mice as well as elevated the deoxycholic acid (DCA) and lithocholic acid (LCA) in the colon compared with those of the imiquimod (IMQ)-treated mice. Meanwhile, B. breve CCFM683 increased the relative abundance of DCA-producing Lachnoclostridium and diminished the harmful Desulfovibrio and Prevotellaceae UCG001. Additionally, the farnesoid X receptor (FXR) in the skin was activated and the expression of the Toll-like receptor 4 (TLR4)/ nuclear factor kappa-B (NF-κB) pathway was inhibited, and the downstream interleukin (IL)-17 and tumor necrosis factor (TNF)-α were downregulated whereas IL-10 was up- regulated. Moreover, the subsequent hyperproliferation of keratinocytes and the dysfunction of the epidermal barrier were improved. In conclusion, CCFM683 administration ameliorated IMQ-induced psoriasis via modulating gut microbiota, promoting the DCA production, regulating the FXR -TLR4/NF-κB pathway, diminishing proinflammatory cytokines, and regulating keratinocytes and epidermal barrier. These findings may be conducive to elucidating the mechanism for probiotics to ameliorate psoriasis and to promote its clinical trials in skin disease.

Streptococcus thermophilus is one of the most prevalent species in stool samples of westernized populations due to continuous exposure to fermented dairy products. However, few studies have explored the effect on host physiology by multiple S. thermophilus strains and considered the inter-strain differences in regulating host. In the present study, we investigated how four S. thermophilus strains influenced the gut microbiota, mucin changes, and host metabolism after 28 days of intervention in conventional mice. The results indicated that the consumption of S. thermophilus affected the host with strain specificity. Among four S. thermophilus strains, DYNDL13-4 and DQHXNQ38M61, especially DQHXNQ38M61, had more effect on host physiology by modulating gut microbiota and host metabolism than LMD9 and 4M6. Ingestion of strains DYNDL13-4 and DQHXNQ38M61 resulted in more remarkable changes in amino acid metabolism and lipid metabolism than that of strains LMD9 and 4M6, which may be related to the elevation of intestinal Bifi dobacterium by DYNDL13-4 and DQHXNQ38M61. The enriched Coriobacteriaceae UCG-002, Rikenellaceae RC9 gut group, and Lactobacillus only in the DQHXNQ38M61 group, had a close relationship with the prominent effect of DQHXNQ38M61 on regulating amino acid and lipid metabolism. In addition, DQHXNQ38M61 had a strong influence on degrading colonic mucin fucose by decreased α-fucosidase activity in feces, and improving mucin sulfation by upregulated Gal3ST2 expression. Comparative genomic analysis revealed that the four S. thermophilus strains belonged to different branches in the phylogenetic tree, and DYNDL13-4 and DQHXNQ38M61 had more genes involved in carbohydrate metabolism, amino acid metabolism, membrane transport, and signal transduction, which may confer the capacity of nutrient utilization and gastrointestinal adaptation of the strains and be associated with their strong regulation in host. Our study provides valuable information for understanding the regulation of host metabolism after consuming different S. thermophilus strains and could facilitate potential personalized applications of S. thermophilus based on strain varieties.

Lactobacillus rhamnosus (Rh) and Lactobacillus reuteri (Re) are well-known probiotic species in inflammatory bowel disease (IBD) research. The variations between these species’ efficacy against colitis, and their model of action in this regard, are intriguing and enable treatment to be individually tailored to patients. In this study, four strains each of Rh and Re were isolated from fecal samples and their draft genomes were sequenced. The anti-colitis activities of both strains involved various aspects of intestinal immune, physical, chemical, and biological barrier function. Strikingly, the tested strains exhibited considerable interspecies and intraspecies specificity in colitis amelioration. Rh strains significantly outperformed Re strains in terms of short-chain fatty acid synthesis. Nevertheless, Re strains were more effective than Rh strains in inhibiting production of inflammatory factors; promoting production of intestinal mucus, antimicrobial peptides, and tight junction proteins; and supporting the stem cell compartment. This accounts for the anti-colitis outcomes of Re strains being superior to those of Rh strains. In addition, the effective Rh and Re strains were found to express high concentrations of specific carbohydrate metabolism- and prophage-related genes, respectively. Taken together, the results of this study could assist researchers in developing effective therapies for IBD.

Immune checkpoint blockade (ICB) therapeutics are highly effective in cancer immunotherapy, but gastrointestinal toxicity limited the application. Intestinal microbiota plays a crucial role in ICB-associated colitis. 2’-Fucosyllactose (2’FL) is most abundance prebiotic in human milk that can reshape gut microbiota and exert immune regulatory effect. The study aimed to determine the effects of 2’FL on ICB-associated colitis and to uncover the mediating mechanism. ICB-associated colitis was induced by the ipilimumab and dextran sulfate sodium. Oral administration of 2’FL (0.6 g/(kg’day)) ameliorated ICB-induced colitis by enhancing regulatory T cells (Treg) and the M2/M1 ratio of macrophages in colon. 2’FL treatment also increased the expression of tight junction proteins (zonula occludens-1 (ZO-1) and mucin 2 (MUC2)) and antioxidant stress indicators (superoxide dismutase (SOD) and catalase (CAT)). In addition, administration of 2’FL increased the abundance of Bifidobacterium and Lactobacillus, and elevated the levels of microbial metabolites, such as indole-3-lactic acid (ILA), which activated the aryl hydrocarbon receptor ligands (AHR) pathway. The protective effect of 2’FL was abolished upon depletion of gut microbiota, and ILA treatment partially simulated the protective effect of 2’FL. Notably, 2’FL did not exhibit inhibition of antitumor immunity. These f indings suggest that 2’FL could serve as a potential protective strategy for ICB-associated colitis by modulating the intestinal microbiota and bacterial metabolites.

The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains. Thus, 6 B. coagulans strains were tested in the present study using an irritable bowel syndrome (IBS) animal model to determine whether the IBS-alleviating effects of B. coagulans strains are strain-specific. The results of this study showed that the ingestion of B. coagulans GBI-30, 6086, and B. coagulans CCFM1041 significantly alleviated IBS symptoms in mice. In contrast, other B. coagulans strains showed no or limited alleviating effects on IBS symptoms. According to our experimental results, the two main common features of these strains were as follows: 1) The resistance of vegetative cells to bile salts, and 2) ability to synthesize specific lipids and secondary metabolites. Screening strains based on these two indicators may greatly reduce costs and provide a basis for mining new functional B. coagulans strains. Our results also suggest that administration of B. coagulans could significantly regulate microbiota dysbiosis in animal models. Moreover, the close relationships between the gut microbiota, gut microbiota metabolites, and IBS were further confirmed in this study.

Gut microbiome is indispensable for maintaining normal brain function. Specifically, gut microbiota plays a causal role in sleep deprivation (SD)-induced cognitive impairment. In this study, neurobehavioral effects of the Bifidobacterium breve strain (CCFM1025) were assessed in sleep-deprived mice. CCFM1025 improved the body weight and food and water intake of the mice. It also alleviated SD-induced cognitive behavioural abnormalities (in the novel object recognition test), but did not show beneficial effects on mood- and spatial memory-related behaviours. CCFM1025 significantly altered the gut microbial composition and genome function. Key microbial metabolites that may regulate sleep function were also identified, such as isovaleric acid and γ-aminobutyric acid in the gut and purine metabolites in the serum. Those metabolites may participate in gut-brain communication by acting on the striatal melatonin system, for example to increase melatonin levels, and by regulating the expression of circadian clock genes such as those encoding the adenosine A2A receptor and period circadian regulator 1. Collectively, administration of probiotics alleviated cognitive impairment and circadian rhythm disturbance induced by SD via modulation of gut microbiome and its metabolites. These findings may help guide the treatment of insomnia or other sleep disorders via dietary strategies.

Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease (NAFLD). The effects of two strains of Limosilactobacillus mucosae on NAFLD were investigated in this study. Four-week-old male C57BL/6J mice were divided into 4 groups (n = 8 per group, Control, Model, FZJTZ26M3, FGSYC17L3). L. mucosae FZJTZ26M3 reduced the mice’s body weight, liver weight, and adipose tissue weight after 12 weeks of therapy. According to serum analysis, total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol significantly decreased after L. mucosae FZJTZ26M3 intervention. Liver pathology showed that L. mucosae FZJTZ26M3 was effective to ameliorate lipid deposition in NAFLD mice. Additionally, the expression of the gene related to lipid metabolism in the liver and adipose tissue was analyzed, and the results indicated that L. mucosae FZJTZ26M3 could alleviate NAFLD by regulating lipid metabolism. Furthermore, the results of 16S rRNA gene sequencing revealed a drop in the relative abundance of Ruminococcaceae, which is linked to inflammation, but the relative abundance of a potential probiotic Akkermansia significantly increased after L. mucosae FZJTZ26M3 intervention. Generally, L. mucosae FZJTZ26M3 could be a candidate to prevent NAFLD.

Lipid metabolism disorders commonly occur during menopause. Estrogen deficiency has been shown to lead to excessive energy intake and abnormal lipid metabolism in ovariectomized rats, resulting in obesity. Probiotics exhibit anti-obesity properties, and their underlying mechanism has been widely reported. In this study, we demonstrated the metabolic benefits of Lactobacillus plantarum CCFM1180 in suppressing appetite, controlling body weight, correcting obesity-induced abnormalities, enhancing liver lipid metabolism, and protecting liver function in estrogen-deficient rats. The mechanisms associated with the anti-obesity and antidyslipidemia effects of CCFM1180 on estrogen-deficient rats were clarified. The results showed that CCFM1180 dramatically reduced food intake by activating the expression of estrogen receptor alpha (ERα) and increasing the level of leptin in abdominal adipose tissue. These changes, combined with the increased butyrate concentration and recovered bile acid structure, helped enhance lipid metabolism. Additionally, CCFM1180 treatment was found to be safer than exogenous estrogen supplementation. Thus, L. plantarum CCFM1180 could be considered a new therapeutic strategy for preventing and alleviating menopausal lipid abnormalities.

Blautia has attracted attention because of its potential efficacy in ameliorating host energy metabolism and inflammation. This study aims to investigate the influences of Blautia producta D4 on colitis induced by dextran sulfate sodium (DSS) and to reveal the underlying mechanisms. Results showed that B. producta D4 intervention significantly relieved body weight loss, and suppressed the elevation of pro-inflammatory cytokines (including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)) and excessive oxidative stress (myeloperoxidease (MPO) activity, superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) level) in colitis mice. Moreover, the concentrations of tight junction proteins (occludin, claudin-1, and ZO-1) related to the intestinal barrier were obviously elevated, and colitis-related TLR4/NF-κB pathway activation was remarkably inhibited after B. producta D4 intervention. The intestinal microbial disorder was evidently ameliorated by increasing the relative abundance of Clostridium sensu stricto 1, Bifidobacterium, GCA-900066225, Enterorhabdus, and reducing the relative abundance of Lachnospiraceae NK4A136 group. In conclusion, oral administration of B. producta D4 could ameliorate DSS-induced colitis by suppressing inflammatory responses, maintaining the intestinal barrier, inhibiting TLR4/NF-κB pathway, and regulating intestinal microbiota balance. These results are conducive to accelerate the development of B. producta D4 as a functional probiotic for colitis.

The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease (AD), a neurodegenerative disease characterised by behavioural and cognitive impairment. However, most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements. Here, we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment (EE) training. In this study, we found that compared with EE or B. breve treatment alone, B. breve intervention combined with EE amplified its neuroprotective effects on AD mice, as reflected by improved cognition, inhibited neuroinflammation and enhanced synaptic function. Moreover, using microbiome and metabolome profiling, we found that the combination of B. breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes. Finally, by integrating behavioural and neurological data with metabolomic profiles, we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions. Collectively, combined B. breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome. Our findings provide a promising multidomain intervention strategy, with a combination of dietary microbiome-based and lifestyle-targeted interventions, to promote brain function and delay the progression of AD.

Akkermansia muciniphila play an important in ameliorating obesity but is not allowed for direct consumption in most countries. To date, microbiota-directed foods selectively promote the targeted human gut microbes, providing a strategy for A. muciniphila enhancement. Multiple studies have indicated the potential regulation of the polyphenol on A. muciniphila. Therefore, a polyphenol screening based on A. muciniphila upregulation was performed in mice. Chlorogenic acid (CGA) exhibited a greater response to A. muciniphila upregulation. Furthermore, we found that CGA did not directly promote A. muciniphila growth or mucin secretion. Microbiome and metabolomics revealed that the increased abundance of A. muciniphila resulted from the inhibition of CGA on Desulfovibrio and Alistipes and the influence of docosahexaenoic acid, β-hydroxybutyrate, and N-acetyl-lactosamine. Finally, to confirm the regulation of CGA on A. muciniphila under disease conditions, high-fat diet-fed mice were established. The results showed CGA promoted A. muciniphila growth, and we expectedly found that CGA suppressed the augment in body weight of mice, significantly attenuated adipose tissue abnormality, provided liver protection and improved gut barrier integrity. These results suggest that CGA inhibits the development of obesity. Overall, our results indicate that microbiota-directed food is a promising approach for the treatment of obesity.

Stachyose is a prebiotic that traditionally extracted from plants, such as vegetable. It has been demonstrated to alleviate intestinal inflammation by regulating gut microbiota, but the mechanism has been unclear. This research aims to detect the potential mechanism of stachyose in alleviating the severity of ulcerative colitis (UC). The results indicated that the administration of stachyose could recover the body weight, protect against the colonic tissue damage, reduce the pro-inflammatory cytokines levels, and reverse the histological abnormalities in UC mice. Oral stachyose could restore DSS-induced disturbance in intestinal bacteria. Besides, the metabolome result of serum samples showed that stachyose treatment significantly altered serum metabolites against inflammatory responses in colitis mice. Also, a significant correlation can be found between 23 metabolite biomarkers and 18 differential genera. Our results provided a strong foundation for the future study of the protective role of stachyose in maintaining intestinal homeostasis.

Akkermansia muciniphila, one of the most promising next-generation probiotics, was reported to exhibit beneficial modulatory effects on the gut barrier. However, the strain-specific and underlying regulatory mechanisms of this species on gut barrier function were not well studied. Therefore, this study evaluated the protective effect of A. muciniphila strains on the intestinal barrier and investigated the mode of action and material basis of this modulatory effect. We first confirmed the strain-specific effects of A. muciniphila on intestinal barrier regulation and found that this phenomenon may be explained by the different abilities of strains to affect tight junction protein expression in enterocytes. Comparative genomic analysis proved that the ability of A. muciniphila to regulate the intestinal barrier was exerted in part by the functional genes (such as COG0438, COG0463, and COG2244) related to the synthesis of cellular surface proteins. The role of these surface proteins in intestinal barrier regulation was further verified by strain-comparative experiments in animal and cell models and surface protein removal trials. This study confirmed the different effects of A. muciniphila strains on gut barrier modulation and provided molecular and genetic targets for the screening of A. muciniphila strains with superior protection against gut barrier dysfunction.

This meta-analysis of randomized controlled trials aimed to evaluate the effects of probiotic supplementation on glucose homeostasis in patients with polycystic ovary syndrome (PCOS). The meta-analysis was performed in accordance with the Cochrane Handbook guidelines and relevant the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria. Of 825 identified reports, 11 randomized clinical trials were included in the meta-analysis. An analysis of pooled extracted data revealed that supplementation with probiotics significantly decreased fasting blood glucose (FBG, n = 7; standardized mean difference (SMD) = −0.40; 95 % confidence interval (CI): −2.02, −0.02; P = 0.04) and insulin levels (n = 6; SMD = −0.57; 95 % CI: −0.89, −0.25; P = 0.0004) and the homeostatic model assessment of insulin resistance (n = 7; SMD = −0.64; 95 % CI: −0.96, −0.31; P = 0.0001) while increasing the quantitative insulin sensitivity check index (QUICKI, n = 5; SMD = 0.58; 95 % CI: 0.08, 1.09; P = 0.02) in patients with PCOS. The FBG-reducing effect decreased as the baseline body mass index (BMI) and mean age of the participants increased. Indeed, a greater number of bacterial species and a higher bacterial dose were shown to reduce QUICKI effectively. The systematic review indicated that probiotic supplementation may help to control glucose homeostasis in adults with polycystic ovarian syndrome.

Studies have determined the immunomodulatory activities of cell-surface polysaccharides of lactic acid bacteria (LAB) and Bacteroides; however, the mechanisms, synthesis, regulation, structure, and functional links have not been systematically discussed. We first introduce the structure of the capsular polysaccharides (CPSs) of commonly studied probiotics and Bacteroides. Wzx-Wzy dependent and ATP-binding cassette (ABC) transporter-dependent pathways are the two main biosynthesis and secretion of CPS pathways. The genes known to be associated with these two pathways are mainly those associated with priming glycosyltransferase (pGT); a variable number of genes encoding for different glycosyl transferases (GTs); Wzx/Wzy-encoding enzymes related to flippases and polymerases; and ABC-transporter genes. In addition, the effects of CPSs on host immunity as well as their related underlying mechanisms are described. Surface polysaccharides on probiotics can serve as a mask to aid in their escape from attacks from the host’s immune system. In turn, they also exhibit immunomodulatory activities, such as strengthening the functions of macrophages, promoting the maturation of antigen-presenting cells, and inducing regulatory T cells. All of these effects of cell-surface polysaccharides exhibit their significant protective properties in immunocompromised diseases, such as colitis, arthritis, and dermatitis. Finally, we focused on their structure and functional links.

This study was performed to determine the effects of bacteriocin-producing and non-bacteriocin-producing Pediococcus acidilactici strains on the immune system and intestinal flora of normal mice. Two P. acidilactici strains with antibacterial activity (P. acidilactici CCFM28 and CCFM18) were obtained based on the inhibition-zone assay. The produced components were identified as bacteriocins through protease treatment, pH adjustment and hydrogen peroxide treatment. Bacteriocin-producing and non-bacteriocin-producing P. acidilactici strains (P. acidilactici CCFM28, CCFM18 and NT17-3) caused significant changes in serum immune factors and intestinal flora of normal mice. After 14 days of intervention, the relative abundance of Firmicutes was significantly decreased, but that of Proteobacteria was significantly increased at the phylum level. At the genus level, the administration of three P. acidilactici strains resulted in the downregulation of Blautia and the upregulation of Ruminococcus and Lactobacillus. Furthermore, there were also different regulations on some probiotic strains, such as Bifidobacterium, Coprococcus and Akkermansia, which were closely related to the antibacterial ability of the bacteriocin and the type of strain. The results indicated that the intervention of different P. acidilactici strains could differently change the structure of intestinal flora in normal mice, which provided theoretical guidance for the selective use of bacteriocin-producing strains for health regulation in the future.