Probiotics play a crucial role in regulating the gut microbiota and enhancing immune response. Oral administration of probiotics modulates intestinal microbiota composition and immune homeostasis. In this study, we investigated the immunoregulatory effect of Lacticaseibacillus rhamnosus LRa05 on cyclophosphamide (CTX)-induced immunosuppressive mice. The results showed that oral administration of LRa05 reduced weight loss, restored immune organ indices, and maintained the structural integrity of the intestinal tissue in CTX-treated mice. Moreover, oral administration of LRa05 exhibited immune-modulating properties by promoting the secretion of cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-10, and secretory immunoglobulin A) in serum. Moreover, the analysis of 16S rRNA amplicon sequencing revealed that LRa05 increased gut microbiota diversity and regulated its composition. In detail, LRa05 intervention restored the Firmicutes/Bacteroidota ratio and significantly increased the relative abundance of Lachnospiraceae_NK4A136_group, Oscillibacter, Alloprevotella, Parasutterella, and Roseburia in immunocompromised mice. Conversely, the abundances of Helicobacter, Bacteroides, and unclassified_Desulfovibrionaceae were significantly decreased after administration of LRa05. Based on these findings, orally administered LRa05 could effectively maintain intestinal microbiota homeostasis and regulate immunity, suggesting the potential of L. rhamnosus LRa05 as a candidate probiotic strain in the application of dietary supplement. PRACTICAL APPLICATION: Supplement with L. rhamnosus LRa05 can improve immunity, regulate gut microbiota and promote body health.
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