Mild cognitive impairment (MCI) represents a critical transitional phase in Alzheimer's disease progression and constitutes a vital intervention window for delaying disease onset. With accelerating population aging, the demand for MCI prevention and management has become increasingly urgent, rendering the exploration of safe and effective early interventions of substantial clinical and societal importance. Building upon prior animal studies demonstrating the cognitive-enhancing potential of Bifidobacterium breve CCFM1179, this randomized, double-blind, placebo-controlled trial evaluated its clinical efficacy through a 12-week intervention in MCI subjects. Concurrently, alterations in gut microbiota, serum, and fecal metabolites were examined to elucidate potential mechanisms. Results demonstrated that compared with placebo, CCFM1179 significantly improved Montreal Cognitive Assessment scores, particularly in visuospatial/executive and naming domains, accompanied by elevated serum brain-derived neurotrophic factor (BDNF) levels. Gut microbiota α-diversity remained stable, yet β-diversity exhibited marked separation. Post-intervention abundance increased in genera including Prevotella, Coprococcus, and Barnesiella, whereas Megamonas, a genus associated with metabolic abnormalities, decreased. Metabolomic analyses revealed substantial alterations in both gut and serum metabolites, with differences predominantly concentrated in amino acid and tryptophan metabolic pathways. Notably, elevated levels of indole-3-propionic acid (IPA) and indole-3-carboxaldehyde (IAld) correlated positively with BDNF, while quinolinic acid decreased. These findings suggest that Bifidobacterium breve may enhance cognitive function by promoting protective indole-derived metabolic pathways and modulating gut-brain axis metabolic signaling. This study provides clinical evidence supporting microbiome-based interventions for MCI and highlights the potentially central role of tryptophan metabolism in cognitive improvement.

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.

Probiotics display estrogen-upregulating properties, yet the underlying mechanisms remain unclear. Herein, we investigated the therapeutic effects of five Bifidobacterium adolescentis strains on ovariectomized (OVX) rats. Among them, strains FHNFQ27M3 (CCFM1506) and FJSWXJNDX6M19 (CCFM1507) administration in OVX rats exhibited significant protective effects through increasing estrogen level and ameliorating pathological parameters, respectively. While FHNFQ27M3 significantly reduced appetite and alleviated abdominal obesity. Both effective strains (FHNFQ27M3 and FJSWXJNDX6M19) significantly altered the gut microbial composition by modifying the Firmicutes/Bacteroidetes ratio and increasing the abundances of Streptococcus, which was associated with elevated production of the short-chain fatty acid. Furthermore, serum metabolomic profiling revealed enhanced amino acid biosynthesis, with tryptophan concentration showed a significant negative correlation with estrogen level. Mechanistically, both strains promoted estrogen biosynthesis through upregulating CYP19A1 activity in adrenal glands. This study provided new insights into the gut microbiota-estrogen axis and highlight the potential of probiotic-mediated metabolic modulation as a viable therapeutic strategy for estrogen deficiency-related disorders.

Non-alcoholic fatty liver disease (NAFLD) is intricately linked to dysregulated hepatic lipid metabolism and gut microbiota imbalances. This study explores the potential mechanisms by which AEN, a lignan-rich extract from Myristica fragrans Houtt., alleviates NAFLD by affecting gut bacteria, bile acid metabolism, and fecal chemical composition. We demonstrate that AEN prevents weight gain, lipid accumulation, and enhances liver function in mice subjected to a high-fat diet. Utilizing a multi-omics strategy that includes microbiome analysis and metabolomics, we observed significant shifts in gut microbial composition and fecal metabolites, notably an increase in lithocholic acid, taurocholic acid, and the ratio of non-12-OH to 12-OH conjugated bile acids. These metabolic changes were accompanied by a decrease in bile acid metabolism-related enzymes, such as bile salt hydrolase, in the AEN group compared to the high-fat diet group. Moreover, AEN downregulated the farnesoid X receptor-fibroblast growth factor 15 pathway in the intestine, promoting the alternative bile acid synthesis pathway. The elucidation of the correlation between changes in the microbiome and fecal metabolites suggests that AEN modulates specific gut microbes, thereby influencing bile acid metabolism. This modulation was evident in the increased abundance of beneficial bacteria related to bile acid production, such as Parabacteroides and Bilophila, and the decreased abundance of harmful bacteria like Helicobacter and Streptococcus. Network pharmacology and GC ¡Á GC-TOF-MS suggested that licarin A and B could be key bioactive lignans in AEN. These findings underscore the potential of AEN in countering NAFLD by targeting the gut-liver axis, offering a novel therapeutic avenue for NAFLD management.

The abundance of Lactiplantibacillus plantarum species was found to be decreased in polycystic ovary syndrome (PCOS) patients, indicating this species may play a superior role in PCOS treatment. Here, the potential of six Lp. plantarum strains in reducing PCOS symptoms was assessed in a rat model. Lp. plantarum FXJKS21M3 (F21M3) intervention alleviated abnormal ovarian morphology and restored progesterone and luteinizing hormone levels in rats. Butyrate was not involved in this curative effect on PCOS symptoms. Dysbiosis of specific gut microbes, including Prevotellaceae_Ga6A1_group, Candidatus_Saccharimonas, and ASF356, was restored by Lp. plantarum F21M3 intervention. Enrichment of Bifidobacterium was also observed in Lp. plantarum F21M3-treated rats. The impact of Lp. plantarum F21M3 on the serum metabolome was more remarkable than that on the fecal metabolome. According to enrichment analysis of differential metabolites, the progestational hormone biosynthesis pathway was enriched after Lp. plantarum F21M3 administration. These results demonstrated that Lp. plantarum species may alleviate PCOS symptoms by regulating gut microbiota and facilitating progestational hormone biosynthesis.

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.

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. These findings provide a greater understanding of the pathogenesis and new targets for microecological interventions by mediating tryptophan metabolism in GDM.

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.

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, Bifidobacterium breve, and Bifidobacterium longum on neonatal rats infected with Salmonella enterica serovar 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 3 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.

A pseudo-germ-free mouse model was constructed using broad-spectrum antibiotics (ABX) to investigate their effects on intestinal motility and the enteric nervous system (ENS) in mice. Bifidobacterium bifidum CCFM1167 was used as a positive strain, and another four B. bifidum strains were screened and evaluated for their regulatory effects on intestinal dysfunction and the ENS. 16S rDNA gene sequencing was used to detect changes in the gut microbiota, and hematoxylin-eosin (H&E) staining and real-time polymerase chain reaction (PCR) were employed to characterize the damage of the ENS and the intestinal barrier. The results showed that ABX treatment significantly affected the intestinal structure and function of mice, leading to altered intestinal morphology, slowed motility and increased fecal water content, accompanied by a severe imbalance in the gut microbiota and damage to the ENS and the intestinal barrier. After intervention with B. bifidum CCFM1389, a significant reduction in total intestinal transit time was observed, and fecal water content returned close to the normal level, along with the alleviation of intestinal motility disorders. Additionally, CCFM1389 significantly increased the gene expression levels of specific markers for colonic neurons (PGP9.5) and enteric glial cells (S100β and GFAP), indicating a repairing effect on the ENS. CCFM1389 also significantly elevated the gene expression of tight junction proteins (Occludin, Claudin-3 and ZO-1), alleviating intestinal barrier damage, and its effect was more pronounced than that of the positive strain CCFM1167. Furthermore, CCFM1389 regulated the structure and composition of the gut microbiota, maintaining intestinal microbial homeostasis. Spearman correlation analysis indicated that CCFM1389 effectively modulated ABX-induced intestinal motility disorders, possibly by increasing the increase in the relative abundance of beneficial bacteria such as Akkermansia, Bifidobacterium, and Lachnoclostridium while decreasing the relative abundance of pathogenic bacteria such as Escherichia_Shigella and Enterococcus, thereby repairing the ENS and the intestinal barrier and regulating intestinal motility.