Zhangming Pei

Antibiotics can significantly disrupt gut microbiota homeostasis, reducing microbial diversity and causing dysbiosis associated with health issues. Gut biofilms play a critical role in resilience and stress tolerance of the intestinal ecosystem. Mucosal microbial communities also help restore the gut microbiota after interventions like probiotics, antibiotics, or fecal transplants. Previously, we developed a core bacterial consortium with strong in vitro biofilm-forming and stress-resilient properties, but its colonization ability and in vivo function remained unclear. In this study, we first validated the in vivo biofilm formation of the microbial consortium using a germ-free (GF) mouse model, then introduced single-, dual-, and multi-strain combinations with varying biofilm-forming abilities into specific-pathogen-free mice to assess their potential for recovering antibiotic-disrupted gut microbiota. Our findings indicate that the robust, in vitro–selected consortium continued to form substantial biofilms in GF mouse intestines. 16 S rRNA sequencing showed that, compared to single- or dual-strain treatments, administering the core consortium significantly increased microbial richness and diversity. The gut microbiota of consortium-treated mice more closely resembled healthy controls, suggesting the core consortium has superior potential to restore healthy gut microbiota. Overall, our research demonstrates the core consortium markedly improves gut microbiota resilience to antibiotic-induced disruptions in mice, accelerates restoration of health-associated taxa, and reestablishes gut homeostasis. This approach could transform probiotic interventions from passive supplementation to active ecological engineering, providing a theoretical and experimental basis for next generation of engineered probiotics and microbiome restoration therapies.

Background: Hypoxic environments significantly impair exercise performance, whilst existing interventions are often limited by adverse effects or insufficient efficacy. Objectives and Methods: This study employed network meta-analysis to screen plant bioactive compounds that effectively enhance exercise performance under hypoxic conditions, with subsequent validation of the efficacy and underlying mechanisms of their combined formulations through animal experiments. Results: Results from hypoxic mouse experiments demonstrated that supplementation with the plant bioactive compound combination significantly improved exercise performance, as evidenced by increased weight-loaded swimming time and limb grip strength. Differential metabolite analysis revealed that the intervention altered key metabolic pathways, including the biosynthesis of unsaturated fatty acids and the metabolism of arginine and proline. Supplementation with the plant bioactive compound combination modulated short-chain fatty acid (SCFA) production by gut microbiota, decreased levels of lactic acid (LA), lactate dehydrogenase (LDH), and creatine kinase (CK), maintained blood glucose levels before and after exercise, and increased muscle and hepatic glycogen reserves. These effects collectively improved exercise endurance and performance in mice under hypoxic conditions. Conclusions: The findings provide novel insights into developing functional interventions to enhance exercise performance in hypoxic environments.

Fermented milk represents an excellent carrier for probiotics, and the incorporation of different carbon sources during fermentation can profoundly affect microbial metabolism. Based on our previous finding that Lactobacillus helveticus DYNDL_20-5 produces fucose-containing exopolysaccharides (EPS), we hypothesized that fucose supplementation could further enhance its metabolic activity and improve fermented milk quality. Thus, this study systematically investigated the impact of culturing L. helveticus DYNDL_20-5 with fucose (CMF5) on the quality characteristics and metabolic profiles of fermented milk. Compared to the control group without fucose and L. helveticus (CM), the CMF5 group demonstrated that L. helveticus effectively utilized fucose to promote acid production, enhance the fermentation process, increase microbial abundance, and enrich beneficial genera. Furthermore, the CMF5 group exhibited significantly improved textural properties, including enhanced viscosity and gel strength. Metabolomic analysis revealed that the addition of fucose and L. helveticus significantly influenced the metabolism of organic acids, fatty acids, and amino acids during milk fermentation, leading to increased concentrations of various metabolites associated with sensory quality, nutritional value, and health-promoting benefits. The findings of this study provide valuable insights into the synergistic effects of L. helveticus DYNDL_20-5 and fucose on fermented milk quality, offering a theoretical foundation for the development of novel functional dairy products with enhanced nutritional and sensory attributes.

Immunodeficiency presents a significant clinical challenge in contexts such as tumour radiotherapy, chemotherapy, and organ transplantation. Current therapeutic interventions are constrained by single-target approaches and substantial adverse effects. As natural bioactive compounds, the immunomodulatory activities of Lactobacillus exopolysaccharides (EPS) are intimately linked to their monosaccharide composition. Mannose and fucose, two rare functional monosaccharides, fulfil critical roles in physiological processes including immune recognition and inflammatory regulation. However, the functional optimisation of EPS through mannose and fucose enrichment remains incompletely characterised. This study established a cyclophosphamide (CTX)-induced immunodeficient mouse model to investigate the immunomodulatory effects of mannose-enriched and fucose-enriched EPS derived from Lactobacillus helveticus. Intervention efficacy was evaluated through a comprehensive assessment of immune organ indices, cytokine profiles, histopathological alterations, and gut microbiota composition. Both mannose-enriched and fucose-enriched EPS significantly elevated splenic indices and ameliorated white pulp atrophy. Furthermore, these EPS variants restored cytokine homeostasis in serum and small intestinal tissues, attenuated hepatic steatosis, and restructured the gut microbiota by enhancing microbial diversity, increasing Firmicutes abundance, and elevating the relative proportions of Bacteroides, Faecalibacterium, and Bifidobacterium. Collectively, mannose-enriched and fucose-enriched EPS from Lactobacillus helveticus alleviated CTX-induced immunodeficiency through multiple mechanisms, including restoration of immune organ integrity, modulation of cytokine networks, and re-establishment of gut microbiota homeostasis. This study provides a theoretical foundation for developing immunomodulatory functional foods and offers novel insights into the microbiota-immunity axis in immune regulation.

The elderly population is prone to osteoporosis, owing to the deterioration of the skin, liver, and kidney functions. Vitamin D (VD) supplementation has a limited effect, and VD deficiency is mostly treated with medication. Several studies have shown that the gut microbiota alters intestinal VD metabolism and that probiotic supplements can influence circulating VD levels. Therefore, in the present study, we screened a strain of Bifidobacterium longum FSHHK13M1 that can increase the level of VD metabolites in the fermented supernatant species in vitro by modeling fecal bacterial fermentation. The results showed that FSHHK13M1 intervention significantly increased the serum levels of 1,25-dihydroxy VD and osteocalcin. It activated the expression of the VDR, OPG, Wnt10b/β-catenin, and Runx2/Osterix pathways and inhibited the expression of RANKL/RANK pathway. Furthermore, there was an enhancement in the quantity of bone trabeculae and the proportion of bone volume. Concurrently, the gut microbiota in mice with osteoporosis exhibited signs of imbalance. FSHHK13M1 intervention increased the relative abundance of specific bacteria, such as Faecalibaculum rodentium , Limosilactobacillus fermentum , Bifidobacterium pseudolongum , and Akkermansia muciniphila . These results suggest that B. longum FSHHK13M1 alleviates retinoic acid-induced osteoporosis symptoms by modulating related genes, regulating the intestinal flora and increasing the level of active VD. IMPORTANCE: Osteoporosis is a systemic metabolic disease in which the patient’s bone mass decreases for a variety of reasons, and the microstructure of the bone tissue is altered, leading to an increase in bone brittleness and susceptibility to fracture. Osteoporosis is almost always present in the elderly population, and fractures from falls are an important predisposing factor for mortality risk in the elderly population. Supplementation is quite limited for them as they are not able to utilize vitamin D well due to declining liver, kidney, and skin functions. In the present study, a strain of Bifidobacterium longum probiotic was found to increase the levels of the active form of vitamin D and ameliorate osteoporosis. This may play an important role in preventing osteoporosis and reducing fracture risk in the elderly.

Prolonged high-intensity exercise consumes significant energy, leading to fatigue and decreased performance. This study explores the effects of Bifidobacterium adolescentis CCFM1066 on exercise performance, gut microbiota, and its metabolites in mice. The results of the mouse experiments showed the mice which were intervened by Bifidobacterium adolescentis CCFM1066 have a significant increase in exercise performance, including forceful swimming time, fatigue baton turning time, and forelimb grip strength. Through metagenomic sequencing and differential metabolites, analysis indicated that the intervention of CCFM1066 increased Lachnospiraceae bacterium, Parabacteroides goldsteinii, Bacteroides xylanisolvens, and Bifidobacterium adolescentis and altered the key metabolic pathways including protein digestion and absorption and biosynthesis of amino acids. Supplementation with CCFM1066 modulates the production of short-chain fatty acids (SCFAs) and fatty acid amides (FAAs) by gut microbiota, decreasing levels of lactic acid (LA), blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and creatine kinase (CK) while increasing muscle and hepatic glycogen content, thus reducing central nervous system fatigue and thereby improving exercise endurance and performance. These findings provide new insights into nutritional interventions for sports performance.