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

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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 (Na 2 SeO 3 ).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 Na 2 SeO 3 .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.

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