Huajun Li

Background: Our previous study demonstrated that fatty acid binding protein 2 (FABP2) expression was significantly upregulated in mice fed a high-fat diet (HFD). In the present study we evaluated the effects and therapeutic mechanisms of Golden Bifid, a probiotic mixture Bifidobacterium longum subsp. longum , Streptococcus salivarius subsp. thermophilus and Lactobacillus delbrueckii subsp. bulgaricus (BSL) on HFD-induced obesity and gut microbiota composition. Methods: Male C57BL/6 mice were fed either a normal diet or an HFD. HFD-fed mice were orally administered saline or BSL by gavage. After 6 weeks of treatment, organ indices, blood lipid profiles, fasting blood glucose, gene expression, and gut microbiota composition were analyzed. Results: BSL treatment reduced body weight gain, fasting blood glucose, and epididymal white adipose tissue mass, increased the brown adipose tissue index, and improved serum, fecal, and hepatic lipids profiles in HFD-induced obese mice. BSL also significantly altered the expression of genes involved in lipid metabolism and transport in the jejunum. Specifically, the mRNA expression levels of peroxisome proliferator-activated receptor (PPAR)γ, FABP2, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), and PPAR α were significantly decreased, whereas liver X receptor α (LXR-α) expression was significantly increased. Kyoto Encyclopedia of Genes and Genomes pathway analysis further showed that BSL suppressed fatty acid metabolism and the PPAR signaling pathway. In addition, BSL increased the relative abundance of Rikenellaceae , Bifidobacteriaceae , Barnesiella and Paramuribaculum , while decreasing that of Allobaculum , Blautia and Kribbibacteriaceae . Conclusion: BSL improves obesity and obesity-associated lipid metabolism disorders, modulates gut microbiota, and inhibiting the expression of PPARγ, FABP2, HMG-CoA reductase and PPARα. Clinical trial number: Not applicable.

Background: Dyslipidemia exhibits pronounced sex-related differences, yet the integrated interactions among gut microbiota, host metabolism, and immune responses underlying these sex-related differences remain poorly understood. Methods: We investigated sex-related alterations in gut microbiota composition, lipid metabolism, and inflammatory responses by integrating the re-analysis of a clinical cohort and mouse model in dyslipidemia, alongside isolation and identification of a keystone probiotic strain. Results: High-fat diet (HFD) induced comparable hepatic steatosis and inflammation in both sexes. However, male mice exhibited earlier body weight gain and impaired intestinal barrier integrity (downregulated ZO-1/Occludin). Metabolomics analysis revealed distinct sex-related bile acid metabolic signatures, with females showing increased levels of several bile acids and enrichment of ascorbate and aldarate metabolism, while males exhibited reduced primary bile acids together with enrichment of bile acid biosynthesis and secretion pathways. Depletion of L. johnsonii observed in both clinical cohort and HFD mice was correlated with keystone taxa ( Lactobacillus ) and with lipid, inflammation, and bile acid markers. Moreover, the isolated L. johnsonii DM2420 strain exhibited cholesterol-lowering activity and BSH activity, harbored multiple genes associated with stress adaptation, and its supernatant metabolomics indicated bile acid remodeling in vitro . Conclusion: Collectively, male mice exhibited greater susceptibility than females to HFD-induced dyslipidemia, which may be associated with the depletion of the candidate keystone taxon L. johnsonii in males and with related bile acid metabolic reprogramming. The isolated strain of L. johnsonii DM2420 exhibited a multifunctional profile that underscores its probiotic potential. Our findings preliminarily suggest a potential association between gut microbiota, bile acids, and immune responses in dyslipidemia and highlight the potential of keystone species-based precision strategies for sex-informed interventions.

Dyslipidemia is a core pathological manifestation of lipid metabolism disorders, and dysbiosis of gut microbiota plays a key role in its onset and progression. Building upon our previous findings on the anti-inflammatory and gut microbiota-modulating effects of Lactobacillus johnsonii DM2420, this study further investigated the regulatory effects and underlying mechanisms of this strain in high-fat diet (HFD)-induced dyslipidemia mice. In vitro, L. johnsonii DM2420 significantly inhibited the accumulation of lipids in 3T3-L1 adipocytes. In HFD-fed mice, L. johnsonii DM2420 reduced the serum levels of total cholesterol (TC), low-density lipoprotein (LDL-C) and free fatty acids (FFA), and increased the amount of high-density lipoprotein cholesterol. Furthermore, HFD -fed mice led to significant increases in the levels of TC and TG in the liver and feces, whereas intervention with L. johnsonii DM2420 significantly reduced their levels. L. johnsonii DM2420 may help restore the homeostasis of lipid metabolism because it causes a reduction in the expression of CD36 protein and SREBP1 mRNA, and a decrease in adipogenic markers. Intervention with L. johnsonii DM2420 increased the relative abundance of Adlercreutzia and Bifidobacterium, and reduced the levels of Allobaculum. Allobaculum occupied a central position within the gut microbial network, which implies that it plays a role in the progression of dyslipidemia. Collectively, this study suggests that L. johnsonii DM2420 may improve dyslipidemia through modification of the composition of intestinal microbiota and a decrease in the expression of CD36/SREBP1-related pathways. This research provides theoretical and experimental support for its potential application as a probiotic agent that targets lipid metabolism disorders.

Yuxuan Shi and Huajun Li. J. Microbiol. Biotechnol. 2026;36:1-11. https://doi.org/10.4014/jmb.2601.01009

To explore the regulatory impacts of the probiotic strain Weizmannia coagulans BC-G44 on antibiotic-associated diarrhea (AAD) and the gut microbiota, a mouse model was established. Twenty-four male C57BL/6 mice were selected and randomly divided into four antibiotic treatment groups: normal, model, high-dose, and low-dose. The normal group mice received 0.2 mL normal saline twice a day, while the model, high-dose, and low-dose groups received 0.2 mL of an antibiotic mixture (550 mg∙kg⁻¹ amoxicillin, 450 mg∙kg⁻¹ clindamycin, 400 mg∙kg⁻¹ streptomycin) twice daily to reduce AAD. For the following 5 days, the high-dose and low-dose groups received W. coagulans BC-G44 at 10⁹ and 10⁷ colony-forming units/mL/day, respectively. On the final day, all mice were euthanized for collection of feces, serum, colon and cecum tissues, and cecal contents. W. coagulans BC-G44 alleviated the weight loss and lowered the serum concentrations of lipopolysaccharide and tumor necrosis factor-α, activating the inflammatory response. W. coagulans BC-G44 also significantly reduced the inflammatory cell infiltration and intestinal mucosal injury in the colon and increased the mRNA expression of the Occludin and ZO-1 genes. Furthermore, 16S rRNA sequencing revealed that W. coagulans BC-G44 increased the gut microbiota diversity of AAD mice, with alpha diversity and beta diversity analyses indicating significant differences in species composition between model and W. coagulans BC-G44-treated groups. Among the AAD mice, BC-G44 reduced the relative abundances of Escherichia and Robinsoniella in the low-dose group and Klebsiella in the high-dose group. Metabolomics of W. coagulans BC-G44 culture supernatants, including untargeted metabolites and Kyoto Encyclopedia of Genes and Genomes pathway annotations, revealed changes in metabolic pathways and metabolites relevant to mice. Our findings indicated that W. coagulans BC-G44 alleviates the AAD process in mice by relieving diarrhea symptoms, easing intestinal inflammation, altering intestinal permeability, and improving gut microbiota structure.

Proteus mirabilis, a major catheter-associated urinary tract infection pathogen, forms antibiotic-resistant crystalline biofilms. Our study demonstrates succinic acid’s multimodal inhibition of P.mirabilis via multi-omics analyses. At 15 mM, succinic acid reduced bacterial growth (≥70%) and biofilm formation (≥50%). Metabolomics revealed that succinic acid treatment induces dysregulation in the tryptophan and arginine metabolism, nucleotide biosynthesis, and tricarboxylic acid cycle in P.mirabilis. Transcriptomics revealed downregulated ribosomal genes, oxidative phosphorylation, and efflux pumps, alongside upregulated arginine transport. Proteomics showed suppression of T6SS virulence factors and iron acquisition proteins. We propose that succinic acid reduces K6 acetylation of the histone-like nucleoid structuring protein, enhancing its oligomerization to repress T6SS genes and inhibit biofilm formation. By targeting metabolism, virulence, and stress adaptation, succinic acid circumvents single-target resistance, offering a strategy to combat multidrug-resistant P.mirabilis through biofilm disruption and pathogenicity suppression.

Purpose Galactooligosaccharides (GOS) are widely added to infant formula milk powder. One of these, 2′-fucosyllactose (2′-FL), has many potential applications. This study investigated the immunomodulatory effects of GOS and 2′-FL, alone or in combination, on RAW 264.7 cells, and their impacts on cyclophosphamide (CTX)-induced immunodeficiency in mice. Methods We used lipopolysaccharide (LPS)-treated RAW 264.7 cells and CTX-induced immunodeficient model mice to analyze the effects of GOS, 2′-FL, and the combination GOSFL on apparent indicators, cellular immunity, inflammation, intestinal barrier function, and the gut microbiota and its metabolites. Results In vitro, GOS and 2′-FL promoted cell proliferation and nitric oxide production, and exhibited dose-dependent increases in the secretion of interleukin-10 (IL)-10, IL-6, and tumor necrosis factor-α. In vivo, high-dose administration GOS, 2′-FL, or GOSFL reduced the body weight and spleen index of immune-deficient mice, increased the number of splenic immune cells, alleviated inflammation, and promoted the expression of Occludin, ZO-1, and MUC2 to restore the intestinal mucosal barrier. GOS and 2′-FL each increased the relative abundances of Bacteroidota and Muribaculaceae, while decreasing those of Firmicutes, Lachnospiraceae, and Lactobacillaceae. Spearman correlation analysis revealed correlations between the gut microbiota and serum immune factors, as well as short-chain fatty acids. Conclusion GOS and 2′-FL significantly promoted cytokine secretion in vitro. High doses of GOS or 2′-FL in vivo reversed the adverse effects induced by CTX, modulated the gut microbiota, and boosted the immune response, with combination use producing similar effects. Graphical abstract