Lactobacilli, as the main member of food microorganisms, is an important component of the intestinal microbial community and plays crucial roles in regulating the immune capacity of the body. This review provides a comprehensive exploration of the key components of Lactobacilli-mediated immune regulation effects, including the immunogenic components (peptidoglycan and lipoteichoic acid) and metabolites (short-chain fatty acids, bacteriocins, and exopolysaccharides), which can interact with host immune cell receptors to initiate complex immune signaling pathways. In addition, the immunomodulatory activity can be influenced by multiple factors including species differences, host-related factors (age, physiological conditions, and gut microbiota), and environmental factors (nutrient substrates, temperatures, etc.), and the application strategies including precision probiotic development, gene-editing driven engineering, and nanocarrier systems have also been proposed to enhance the immunomodulatory potential. Finally, this review provides the theoretical basis for microbial intervention in immune-related diseases and offers prospects for applications in the food and pharmaceutical industries.

Codonopsis pilosula polysaccharides have demonstrated multiple biological activities including immune regulation, antitumor, and antioxidant properties. The rapid development and integrated application of multi-omics can facilitate the unraveling of the complex network of immune system regulation. In this study, C. pilosula alkali-extracted polysaccharide (CPAP) were prepared, and their effects on gut microbiota compositions, metabolic pathways, and protein expressions in peripheral blood and solid tumors in mice were further evaluated. The 16S rDNA sequencing results showed that CPAP could effectively promote the enrichment of intestinal Lactobacillus in tumor-bearing mice. In addition, it could be inferred from peripheral blood and solid tumor proteomics results that CPAP might activate T cell-mediated antitumor immune functions by regulating purine metabolism and alleviate tumor-caused inflammation by promoting neutrophil degranulation, finally inducing apoptosis in tumor cells by increasing oxidative stress. These results will provide a theoretical foundation and data support for the further development of CPAP as dietary adjuvants targeting immune deficiency-related diseases.

Codonopsis pilosula polysaccharide (CPP) and rare element selenium (Se) have been proved to exert various biological activities, and our previous study demonstrated that selenium nanoparticles modified with CPP (CPP-SeNPs) possessed significantly enhanced tumor cytotoxicity in vitro. This study aimed to investigated the inhibitory effects of CPP-SeNPs complex on H22 solid tumors via immune enhancement. In this study, the H22 tumor-bearing mice model was constructed, and the potential mechanisms of CPP-SeNPs antitumor effects were further explored by evaluating cytokines expression levels, immune cells activities and tumor cells apoptotic indicators in each group. The results demonstrated that CPP-SeNPs effectively exerted dose-dependent protective effects on the immune organs of tumor-bearing mice in vivo, leading to increase in peripheral white blood cell counts and inhibition of solid tumor growth with inhibitory rate of 47.18% in high-dose group (1.5 mg/kg). Furthermore, CPP-SeNPs treatment significantly elevated the levels of TNF-α, IFN-γ, and IL-2 in mice sera, enhanced NK cell cytotoxicity, augmented macrophage phagocytosis capacity, as well as increased both the amounts and proliferation activity of lymphocyte subsets. CPP-SeNPs improved the immune system’s ability to clear tumor cells by up-regulating Bax expression while down-regulating Bcl-2 expression within solid tumors, indicating the potential activation of mitochondrial apoptosis pathway. Therefore, CPP-SeNPs administration can effectively inhibit tumor growth by enhancing immune response in tumor-bearing mice, which might be relevant to the regulation of gut microbiota short-chain fatty acids metabolisms. These findings could provide theoretical support and data foundation for further development of CPP-SeNPs as functional food and drug adjuvants.

Background:Dendrobium officinale glycolipids (DOG), often left as residues after hot water extraction for polysaccharide production, are often discarded. Methods: This study investigates the optimal extraction of DOG using response surface methodology, focusing on liquid–solid ratios, ethanol concentrations, extraction temperatures, and extraction times, while preliminarily analyzing DOG’s structural properties. Additionally, the differences in antioxidant effects between DOG and ascorbic acid based on intestinal flora metabolism were further evaluated. Results: The optimal parameters for DOG extraction were determined as follows: liquid–solid ratio of 20 mL/g, ethanol concentration of 70%, extraction temperature of 70 °C, and extraction time of 2.5 h, yielding 2.64 ± 0.18%. In addition, DOG was identified as a diglyceride, mainly composed of glucose, mannose, linoleic acid, 9,12,15-octadecatrienoic acid, and presented certain direct free radicals scavenging effects. In animal experiments, unlike the direct free scavenging effects of ascorbic acid, DOG increased intestinal Bacteroides acidifaciens abundance in mice, up-regulated piceatannol expression, and down-regulated 1-naphthol expression, which contributed to antioxidant effects by enhancing the activities of SOD and GSH-Px while reducing MDA content. Conclusions: DOG was a diglyceride isolated from D. officinale residues after hot water extraction, and presented strong antioxidant effects by regulating intestinal flora metabolism. These findings could promote the efficient utilization of D. officinale and support further development of DOG in functional food applications.

Background: Tuber indicum is a rare edible and medicinal ectomycorrhizal fungus, and the polysaccharide fractions have attracted extensive research attention owing to their potent immunomodulatory potential. Objective/Methods: To systematically characterize the structural features and gut microbiota-mediated immunoregulatory mechanisms of water-extracted polysaccharide (TIWP) and alkali-extracted polysaccharide (TIAP) from T. indicum, two polysaccharide fractions were prepared and comprehensively structurally characterized in this study. Results: The maximum molecular weight of TIWP reached 2.65 × 10⁷ Da, which was dominated by glycosidic linkages of →3)-Glcp-(1→, →2,4)-Glcp-(1→ and →3,6)-Glcp-(1→. TIAP possessed a higher molecular weight up to 3.87 × 10⁷ Da, with predominant glycosidic bonds of →3,6)-Glcp-(1→, →4)-Glcp-(1→ and →2,4)-Glcp-(1→. In vivo bioactivity evaluation results demonstrated that both TIWP and TIAP significantly restored the proportions of CD3⁺ T and CD19⁺ B lymphocyte subsets in peripheral blood and spleen, and alleviated pathological damage in splenic and colonic tissues. Distinct regulatory patterns of gut microbiota were observed between the two polysaccharides: TIWP markedly enriched the genera Lactobacillus and Ruminiclostridium, whereas TIAP elevated the relative abundances of Lactobacillus and Alloprevotella. Untargeted metabolomics combined with KEGG pathway enrichment analysis revealed that TIWP and TIAP activated the pantothenic acid and coenzyme A biosynthesis pathway and the linoleic acid metabolism pathway. Conclusions: Collectively, TIWP and TIAP alleviated CTX-triggered immunosuppression through distinct “gut microbiota-metabolite-immunity” regulatory networks due to their structural disparities. This study provides a theoretical basis for the development of gut microecology-targeted functional foods with immunomodulatory functions.

Suillus luteus is a highly prized edible fungus and demonstrates significant potential in the field of bioremediation, particularly for soil restoration and pollution mitigation. However, systematic research on the structural characteristics of the bioactive polysaccharides and regulatory effects on gut microbiota metabolism remains scarce. In this study, S. luteus polysaccharide (SLP) was obtained by hot water extraction and the structural characteristics were systematically determined, as well as the regulatory function on gut microbiota metabolism in a tumor-bearing mice model. Results showed that SLP exhibited an average molecular weight of approximately 1.90 × 10⁶ Da with Fuc:Man:Glc:Gal molar ratio of 0.37:1.00:0.72:0.54. The polysaccharide predominantly employed β-(1→4)-Manp as the backbone with α-(1→3)-Fucp, α-(1→6)-Glcp, and α-(1→6)-Galp as side chains. SLP administration of 200 mg/kg in tumor-bearing mice exerted enrichment effects of intestinal probiotics, including Lactobacillus and Odoribacter, which were associated with alterations in glyoxylate and dicarboxylic acid metabolism, ultimately enhancing CD4⁺ T cell immunity and resulting in a tumor suppression rate of 53.14%. This study provides a theoretical foundation and supporting data for the development of S. luteus polysaccharide in the functional food field.