The neurotransmitter 5-hydroxytryptamine (5-HT), primarily produced by intestinal enterochromaffin cells (EC), relies on Tryptophan hydroxylase (TPH1) for synthesis. Research suggested Bifidobacterium breve CCFM1025's potential in regulating Tph1 gene expression, maintaining 5-HT levels in stressed mice, but its precise mechanisms were unclear. This study used metabolomic techniques to assess probiotic fermentation products, revealing acetate as the crucial element in Bb-CCFM1025's regulation of gut 5-HT synthesis. Further exploration correlated acetate with Tph1 transcription in intestinal organoids. Transcriptomic methods and qRT-PCR validation demonstrated how acetate facilitated 5-HT synthesis and secretion. It unveiled that acetate orchestrates signaling pathways (PI3K-AKT, PLC-pERK, and PLC-IP3-Ca²⁺) within EC cells, enabling 5-HT production. These findings elucidate the biochemical mechanisms behind specific probiotics' effects, aiding in the targeted selection of similar beneficial strains. This study offers theoretical support for choosing probiotics with analogous functionalities based on their physiological impacts.

This randomized, double-blind, placebo-controlled trial evaluated the uric acid (UA)-lowering effect of Limosilactobacillus reuteri CCFM1132 in young males with hyperuricemia. Participants received 1×10¹⁰ CFU of L. reuteri CCFM1132 (n=34) or placebo (n=31) daily for 8 weeks. After the intervention, serum UA concentration significantly decreased, along with a reduction in xanthine oxidase (XOD) activity compared to the placebo group (P < 0.01). Indicators of liver (aspartate transaminase and alanine transaminase) and renal (urea and creatinine) functions improved. Short-chain fatty acid (SCFA) concentrations significantly increased, with an upregulated abundance of SCFA producers (Fusicatenibacter, Ruminococcaceae UCG_014, and Ruminococcus 1) in the gut. Additionally, correlation analysis revealed that concentrations of SCFAs, particularly acetate and butyrate, were strongly negatively correlated with UA concentration and XOD activity. These findings suggest that L. reuteri CCFM1132 relieves hyperuricemia by enhancing the abundance of SCFA producers in the gut to promote SCFA production and by suppressing XOD activity. This study provides a valuable reference for developing new treatments for hyperuricemia

The number of people travelling to high-altitude areas or participating in mountain sports is increasing. For individuals visiting such terrains for the first time, the lack of adaptation to the hypobaric hypoxic environment can lead to the deterioration of gastrointestinal function and barriers. In more severe cases, this lack of acclimatisation may lead to acute high-altitude illness. At present, the prevention and treatment of these issues primarily revolve around strategies such as descending to lower altitudes, oxygen supplementation, and medication. However, the available intervention measures to prevent health problems resulting from high-altitude environments remain limited. In this review, we discuss common altitude-related illnesses, including gastrointestinal problems. Moreover, we explore the potential of commonly used medications and dietary supplements in alleviating altitude-related issues. This review can provide a basis for future research on modulating the gut microbiota for mitigating high-altitude illness.

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.

Gestational diabetes mellitus (GDM) is a disease of glucose intolerance that first occurs during pregnancy. Accumulating evidence underlined a link between gut microbiota dysbiosis and GDM, and microbial metabolites represent a unique way to explore microbiota–host interactions. However, the associations between changes in the gut microbiota and microbial metabolites and immune homeostasis in the GDM pathogenesis remain largely unclear. In this prospective study, the characteristics of gut microbiota in both first trimester (T1) and second trimester (T2 ) were investigated in 46 GDM patients and 44 matched controls. We comprehensively profiled the microbial metabolites using non-targeted metabolomics and quantitatively targeted metabolomics, measurements of inflammatory cytokines and biomarkers of intestinal barrier function, and combined with correlation analysis in T2. Gut microbiota dybiosis was observed in GDM patients in both T1 and T2, and was characterised by the enrichment of multiple potentially harmful bacteria, such as UBA1819 and Erysipelatoclostridium. Besides, alterations in the microbiota were accompanied by a disturbance in tryptophan metabolism, mainly manifested as a shift towards the production of more kynurenine and less indole derivatives. Most importantly, correlation network analysis indicated that overgrowth of potential pathogens and tryptophan metabolism disorder were associated with inflammatory imbalance and disrupted epithelial barrier in GDM patients. Theses findings provide a greater understanding of the pathogenesis and new targets for microecological interventions by mediating tryptophan metabolism in GDM.

Infants exhibit diminished susceptibility to external infections, a phenomenon closely linked to the pervasive presence of the bifidobacterial community within their intestinal tract. Nonetheless, a significant knowledge gap remains concerning the distinct species of bifidobacteria initiating anti-infection immune responses during the early developmental stages. In this study, the impact of early intervention with Bifidobacterium bifidum (B. bifidum), B. breve, and B. longum on neonatal rats infected with Salmonella enterica serovar Typhimurium (S. typhimurium) SL1344 were compared. The study encompasses various immunity levels, including gut immunity, central immunity (thymus), peripheral immunity (spleen), and brain immunity. Following Salmonella infection, significant alterations in neonatal rats were observed in growth and developmental levels, immune markers, cytokine levels, balance of T lymphocyte subpopulations, intestinal barrier function, and blood-brain barrier integrity. Compared with B. breve and B. longum, B. bifidum demonstrated more pronounced efficacy in regulating these physiological processes. By conducting multi-level analyses of gut microbiota, bifidobacterial community, colonic content metabolomics, and serum metabolomics, the significance of B. bifidum's role is underscored, and the immune-enhancing function of messenger metabolites is unveiled. Among these metabolites, γ-L-Glutamyl-L-glutamic acid and Orotic acid were found to be shared by all three species, while Hippuric acid and 1a,1b-dihomo Prostaglandin F2α were unique to B. bifidum, and DL-Arginine was specific to B. longum. Overall, this study has provided novel insights into the intervention and immunomodulation by Bifidobacterium in early-life infections, emphasizing the significant role of B. bifidum.

Obesity is a major focus of researchers due to its increasing prevalence and relationship with other diseases, such as cancer and cardiovascular diseases. Probiotics are active microorganisms and have been proven to alleviate obesity by modulating the microbiota. In this study, we found that oral administration of Bifidobacterium adolescentis CCFM8630 to obese mice inhibited high-fat-diet (HFD)-induced changes in body weight and adipose tissue and alleviated hepatic oxidative stress. Furthermore, B. adolescentis CCFM8630 treatment primarily affected the relative abundances of the phyla Proteobacteria and Actinobacteria, and thereby decreased the production of lipopolysaccharide (LPS) and the occurrence of LPS-related diseases. A high fiber intake increased the abundance of Lactobacillus and the concentrations of short-chain fatty acids in obese mice, but these changes were reversed by B. adolescentis CCFM8630 treatment. In addition, targeted metabolomic analysis and microbiota relationship analysis revealed that B. adolescentis CCFM8630 treatment modified the microbiota of obese mice by promoting the conversion of tryptophan (Trp) to xanthurenic acid, kynurenic acid, tryptamine, indole-3-acetic acid, and indole-3-carboxaldehyde; facilitated the expression of interleukin-17A and the aryl hydrocarbon receptor to generate interleukin-22 in the colon; and upregulated the expression of tight junction proteins, thereby strengthening intestinal barriers. In summary, our findings suggest that the intake of B. adolescentis CCFM8630 may alleviate obesity by modulating the gut microbiota and related Trp metabolism.

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 A_2A 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.

Bifidobacterium longum subsp. infantis (B. longum subsp. infantis) and Bifidobacterium adolescentis (B. adolescentis) play important roles in the guts of infants and adolescents, respectively. In this study, using a neonatal rat model, we compared the protective effects of these two bifidobacterial species against Salmonella infection. The results demonstrated that B. longum subsp. infantis was more effective than B. adolescentis in alleviating the severity of infection in newborn rats exposed to Salmonella enterica serovar Typhimurium strain SL1344. B. longum subsp. infantis attenuated intestinal inflammation and mucosal damage induced by Salmonella infection, as well as protecting intestinal nerves and intestinal barrier function through TLR4/MyD88 signalling. B. longum subsp. infantis also displayed the potential to modulate gut metabolites by promoting the biosynthesis of unsaturated fatty acids (arachidonic acid, eicosapentaenoic acid and α-linolenic acid) and purine metabolism (guanine, adenine, inosine and adenosine), thereby regulating metabolic disturbances. Additionally, the benefits of B. longum subsp. infantis were also observed in the liver, spleen and brain, improving nerve reflexes and suppressing hepatosplenomegaly. Overall, these findings provide novel insights into the prevention and treatment of gut-related diseases in newborns, highlighting the potentially significant role of B. longum subsp. infantis in clinical applications.

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.