Asthma is a prevalent respiratory disease. The present study is designed to determine whether gut microbiota-derived tryptophan metabolites alleviate allergic asthma inflammation in ovalbumin (OVA)-induced mice and explore the effect and potential mechanism therein. Asthma model mice were constructed by OVA treatment, and kynurenine (KYN), indole-3-lactic acid (ILA), in-dole-3-carbaldehyde (I3C), and indole acetic acid (IAA) were administered by intraperitoneal injection. The percent survival, weight and asthma symptom score of mice were recorded. The total immunoglobulin E and OVA-specific (s)IgE in the serum and the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) were detected by the corresponding ELISA kits. The composition of the gut microbiota and tryptophan-targeted metabolism in mouse feces were analyzed using 16S rRNA gene sequencing and targeted metabolomics, respectively. The four tryptophan metabolites improved the percent survival, weight and asthma symptoms of mice, and reduced the inflammatory cells in lung tissues, especially I3C. I3C and IAA significantly (p < 0.05) downregulated the levels of OVA-IgE and inflammatory cytokines. KYN was observed to help restore gut microbiota diversity. Additionally, I3C, KYN, and ILA increased the relative abundance of Anaeroplasma, Akkermansia, and Ruminococcus_1, respectively, which were connected with tryptophan metabolic pathways. IAA also enhanced capability of tryptophan metabolism by the gut microbiota, restoring tryptophan metabolism and increasing production of other tryptophan metabolites. These findings suggest that tryptophan metabolites may modulate asthma through the gut microbiota, offering potential benefits for clinical asthma management.
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.