The immunomodulatory effects of Bifidobacterium lactis XLTG11 on cyclophosphamide-induced immune dysfunction in mice.

Mannatide modulates immune response and gut microbiota in cyclophosphamide-induced immunosuppressed BALB/c mice.

Mannatide, a polysaccharide-based immunomodulator, has been widely used in China to enhance immune function, yet its mechanisms remain underexplored. This study investigated the immunoprotective effects of Mannatide in cyclophosphamide (CTX)-induced immunosuppressed mice, focusing on modulation of the gut microbiota and associated signalling pathways. Results demonstrated that Mannatide restored immune organ indices (spleen and thymus), elevated serum cytokines (IL-2, IFN-γ, TNF-α), improved the CD4+/CD8+ ratio, and upregulated intestinal tight junction proteins (Claudin1, Occludin1, ZO-1). Additionally, Mannatide also attenuated CTX-induced phosphorylation of p38 and JNK and shifted apoptosis-related markers toward a protective profile, as indicated by reduced Bax and increased Bcl-2 expression in splenocytes. Furthermore, increased intestinal TLR4 and p65 mRNA suggests recovery of innate immune signalling rather than a simple anti-inflammatory effect. Gut microbiota analysis revealed a restored Bacteroidetes/Firmicutes ratio and enriched SCFA-producing genera (Parabacteroides, Clostridia-UCG-014), correlating with increased faecal SCFAs (acetate, butyrate). Together, these findings highlight that Mannatide is associated with immune recovery in CTX-treated mice, accompanied by changes in gut microbiota, SCFA production, and immune-related signalling pathways, and provide insights for adjuvant therapies targeting the gut-immune axis.

Immunomodulatory Effects of Lactococcus lactis on the Gut—Pancreas Axis 2257747

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic beta cells by T lymphocytes, resulting in insulin deficiency. Our group has shown unique alterations in the gut mucosa and microbiome dysbiosis in pre-diabetic mice that occur prior to insulin deficiency in Non-Obese Diabetic (NOD) mice. These findings suggest that the gut microbiome may influence the gut mucosa and modulate disease progression. Lymph node sharing between the intestine and the pancreas may play a critical role in determining disease onset. This study investigated the immunomodulatory effects of Lactococcus lactis NCDO 2118 supplementation on 4 weeks female NOD mice treated for 28 days. Major gut microbiota phyla were analyzed by qPCR of fecal DNA, and short-chain fatty acids were determined by liquid chromatography. Secretory IgA (SIgA) was quantified by ELISA, and IgA-bound bacteria (Bac-IgA) and cell populations were analyzed by flow cytometry. L. lactis administration significantly reduced (p = 0.0095) the frequency and severity of pancreatic insulitis, without affecting food or water intake, blood glucose, body weight, intestine size, or SIgA levels. Bac-IgA levels were decreased in treated mice. Innate Lymphoid Cells, Intraepithelial and T lymphocytes profiles were unchanged in the gut, while B cells and plasmocytes were decreased in the Peyer’s patches of treated mice. L. lactis-treated mice displayed a lower proportion of tolerogenic dendritic cells in the spleen and gut-pancreas shared lymph nodes. An increase in total bacteria and Firmicutes, and a reduction in Proteobacteria, were observed in the colon of the treated group, along with higher levels of acetate and lactate. In conclusion, L. lactis NCDO 2118 reduced insulitis in NOD mice and promoted an immunomodulatory profile during T1DM development, likely mediated by alterations in the gut microbiota and the gut—pancreas axis. CNPq, CAPES and FAPEMIG (#RED-00096-22, #RED-00067-23) Mucosal and Regional Immunology (MUC)

Effects of L-selenomethylselenocysteine-fortified milk powder on immune homeostasis, intestinal integrity, and gut microbiota in immunosuppressed mice.

Immunosuppression is strongly associated with impaired intestinal health and perturbations in gut microbial composition. This study aimed to evaluate the regulatory effects of L-selenomethylselenocysteine (L-SeMC) fortified milk powder on immune function and gut microbiota in cyclophosphamide (CTX)-induced immunosuppressed mice, and to compare its efficacy with selenium-enriched yeast (SY) and sodium selenite (Na2SeO3). The results demonstrated that L-SeMC intervention significantly mitigated CTX-induced weight loss and markedly enhanced thymus and spleen indices. L-SeMC effectively boosted splenic lymphocyte proliferation and significantly reduced the serum levels of pro-inflammatory cytokines compared with the model group. Histologically, L-SeMC alleviated pathological damage in the spleen, liver, and intestine, notably restoring jejunal villus height and the villus-to-crypt (V/C) ratio. Moreover, L-SeMC significantly increased gut microbial diversity and was associated with changes in the relative abundance of several taxa, including Odoribacter, Bacteroides, Lachnospiraceae, and Roseburia. L-SeMC exhibited superior efficacy in regulating immune function and alleviating intestinal injury compared with SY and Na2SeO3. These findings suggested that L-SeMC-fortified milk powder may help alleviate CTX-induced immunosuppression and is associated with changes in gut microbial composition under the present experimental conditions, providing preliminary evidence for its potential application in functional dairy products.

Immunomodulatory effects of Sanghuangporus sanghuang polysaccharide SSP1 in cyclophosphamide-induced immunosuppressed mice: associations with gut microbiota, short-chain fatty acids, and metabolic remodeling

Immunosuppression induced by chemotherapeutic agents such as cyclophosphamide (CTX) is frequently associated with gut microbiota dysbiosis. Sanghuangporus sanghuang polysaccharide (SSP1) possesses immunomodulatory potential; however, its effects on mucosal immunity and the gut microbiota remain unclear. In this study, we investigated the immunomodulatory activity of SSP1 in CTX-induced immunosuppressed mice. Mice were treated with different doses of SSP1 orally. We assessed immune organ indices, histopathology of immune organs and colon, oxidative stress, splenocyte proliferation, T-cell subsets, and cytokine production. Additionally, 16S rRNA sequencing was used to analyze gut microbiota composition; targeted analysis was performed on short-chain fatty acids (SCFAs); and untargeted metabolomics was used to evaluate metabolic profiles. Oral administration of SSP1 significantly alleviated immunosuppression in a dose-dependent manner, with the high dose (SSP1-H) showing the most pronounced effects. This was evidenced by restored body weight, increased spleen and thymus indices, improved histopathology, and attenuated oxidative stress. SSP1 promoted splenocyte proliferation, elevated CD45 + leukocytes and CD3 + T cells, enhanced IL-2 and IL-4 production, suppressed IFN-γ secretion, and inhibited LPS-induced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Gut microbiota analysis revealed that SSP1-H increased α-diversity, enriched beneficial bacteria ( Bacteroides and Odoribacter ), and elevated SCFAs (acetate, propionate, and valerate). Correlation analysis showed SCFA levels were positively correlated with antioxidant markers, T-cell subsets, and IL-10, and negatively correlated with pro-inflammatory cytokines. Untargeted metabolomics further indicated that SSP1-H regulated serine, threonine, and taurine metabolism. Collectively, these findings suggest that high-dose SSP1 treatment was associated with coordinated changes in gut microbiota composition, SCFA production, and immune parameters, supporting a potential microbiota–metabolism–immune axis. This implies that SSP1’s protection against CTX-induced immunosuppression is associated with regulating immune cell functions and reshaping the gut microbiota to enhance SCFA production, providing new insights into the immunoregulatory mechanisms of Sanghuang polysaccharides and highlighting their potential as functional food ingredients or immune adjuvants.

Study on the regulatory effect of Bifidobacterium animalis subsp. lactis BLa80 on immune function of healthy mice and pathogenicity in animals.

Bifidobacteria are known for their health-promoting effects, particularly in the context of gut microbiota modulation and immune system support. Bifidobacterium animalis subsp. lactis BLa80 is a novel probiotic strain isolated from human breast milk. This article evaluates the immunomodulatory effects of BLa80 on healthy mice through indicators such as cellular immunity, humoral immunity, monocyte-macrophage phagocytic function, natural killer cell activity, and immunoglobulins in serum. Concurrently, animal pathogenicity tests were conducted to complement earlier safety studies of BLa80. The mice were treated with low, middle and high doses (12.5, 25, 75 mg/kg BW; 0.25 × 106, 0.5 × 106, 1.5 × 106 cfu/d) of BLa80 solution for 30 days. Body weight, organ-to-body weight ratio, cellular immune function (delayed-type hypersensitivity and lymphocyte transformation), humoral immune function (antibody-forming cell and serum haemolysin), monocyte-macrophage phagocytic function (monocyte-macrophage carbon clearance, Peritoneal macrophage phagocytosis of chicken red blood cells) and natural killer cell activity were observed and recorded. Additionally, the contents of IgG, IgM and IgA in serum of mice, as well as the concentrations of cAMP and cGMP in the spleen and serum, were detected. Healthy mice were administered a certain dose of BLa80 solution through both intraperitoneal injection (BLa80 Group: 1 × 107 cfu/d) and oral gavage (BLa80 Group: 1 × 108 cfu/d, 5 × Concentrated BLa80: 5 × 108 cfu/d). After the mice consumed the BLa80 solution, their general health condition, body weight, and mortality were observed and recorded daily. Compared with the blank control group, the haemolysis values of the middle and high dose groups were significantly different ( P < 0.05), and the monocyte-macrophage carbon clearance values of each dose group were significantly different ( P < 0.05). The carbon clearance phagocytic index in all three dosage groups was better than that in the blank control group. Additionally, the IgM levels in all three dosage groups were higher than those in the blank control group, with the high-dose group showing a significant difference compared to the blank control group ( P < 0.05). During the 21-day observation period, the test substance had no adverse effects on the general health of the mice, and there was no statistically significant difference in weight and other indicators compared to the control group ( P < 0.05), with no deaths observed among the mice. Based on the 'Testing and Evaluation Methods for Health Food Functions (2023 Version)', it is determined that Bifidobacterium animalis subsp. lactis BLa80 can enhance the immune function of healthy mice. Concurrently, according to the 'Guidelines on Safety Assessment and Evaluation of Microbial Strains Used as Health Food Raw Materials (2020 Edition, Appendix A)', BLa80 is determined to be non-pathogenic to animals.

Protective effects of Bacillus clausii in cyclophosphamide-induced immunosuppression and intestinal mucositis in rats: histopathological and inflammatory evaluation