The metabolism of branched‐chain amino acids by gut microbiota can improve overall health and may reverse aging. In this study, we investigated Parabacteroides merdae, a gut microbe that is known to catabolise branched‐chain amino acids (BCAAs). Three metabolites of BCAAs isovalerate, 2‐methylbutyrate, and isobutyrate were used to treat D‐gal induced aging mice. The results showed that these treatments could delay aging in mice by providing health benefits in reducing oxidative stress and inflammation, improving muscle capacity, reversing brain acetylcholine levels, and regulating blood glucose. The mechanism was preliminarily explored by combining the gut microbiota metagenome and faecal serum metabolome. Parabacteroides merdae altered the species composition and structure of the gut microbiota in mice. Increasing the abundance of beneficial bacteria, such as Bifidobacterium pseudolongum. Three metabolites affects the gut microbiota and the body's pathways of protein and improves the overall health through a variety of signaling pathways. Overall, regulating the gut microbiota involved in branched‐chain amino acid metabolism to bring health benefits may be a new way of reversing aging.

Background: Despite the known association between chronic inflammation and reduced muscle mass, there is a gap in research regarding the association between the systemic immune-inflammation index (SII) and sarcopenic obesity (SO). This study aims to assess the relationship between SII and SO in middle-aged and elderly adults and the mediating role of triglyceride-glucose index (TyG). Methods: This cross-sectional study involved 2,719 participants aged 45–90 years who underwent health check-ups. SO was evaluated by combining sarcopenia [assessed by handgrip strength and appendicular skeletal muscle index (ASMI)] with obesity (determined by body fat percentage). Association between SII and SO, sarcopenia, and obesity in middle-aged and elderly individuals was examined using multivariable logistic regression, restricted cubic spline analysis, and subgroup analysis. Bidirectional mediation analysis was conducted to determine the direct and indirect effects through SII and TyG. Results: The study included 2,719 participants, of which 228 had SO (8.4%). SO prevalence increased as the SII quartiles rose (P_{for trend} <0.001). SII (per SD increase) had a significantly positive association with SO in both middle-aged individuals (OR = 1.69, 95% CI: 1.43 ~ 1.99) and older adults (OR = 2.52, 95% CI: 1.68 ~ 3.77). The relationship between SII and SO was found to be non-linear (P_nonlinear0.05). Conclusions: Elevated levels of SII were associated with an increased risk of SO in middle-aged and elderly adults, especially in the elderly population, and elevated TyG levels played a role in this relationship.

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.

Introduction: Elderly individuals exhibit heightened susceptibility to osteoporosis, largely attributable to age-related declines in skin, liver, and kidney function. While vitamin D (VD) supplementation is common, its efficacy is often limited, necessitating reliance on pharmaceutical interventions. Research indicates that the intestinal flora significantly influences intestinal VD metabolism, with probiotic supplementation demonstrably impacting circulating VD levels.Methods: We employed an fecal fermentation model to screen bacterial strains. After introducing these strains into osteoporotic mice, we tested the mice’s serum and skeletal indicators. We then conducted a correlation analysis between the mice’s key intestinal microbiota and serum and skeletal indicators.Results and discussion: We identify Bifidobacterium adolescentis CCFM1447 for its capacity to elevate VD metabolite levels within fermented supernatants. It significantly elevated serum concentrations of 1,25-dihydroxyvitamin D. Furthermore, this intervention improved bone microarchitecture, evidenced by increased trabecular number and bone volume fraction. In addition, the intestinal flora of the osteoporotic mice was disturbed. CCFM1447 intervention increased the relative abundance of beneficial bacteria such as Adlercreutzia equolifaciens, Akkermansia muciniphila and Pediococcus acidilactici. And it is enriched with a part of strains that have the ability to transform VD such as Enterococcus faecalis and Pediococcus acidilactici. The above results suggest that B. adolescentis CCFM1447 may alleviate retinoic acid-induced osteoporosis symptoms by modulating the intestinal flora and increasing the level of active vitamin D.

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.

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.