Paraprobiotic Lacticaseibacillus paracasei HY7017 restores gut microbiota homeostasis and short-chain fatty acid production in cyclophosphamide-induced immunosuppressed mice

초록

This study evaluated the protective effects of paraprobioticLacticaseibacillus paracaseiHY7017 (Para-HY7017) on gut microbiota homeostasis and immune responses in cyclophosphamide (CTX)-induced immunosuppressed mice. Para-HY7017 (heat-killed cells, 2spacexspace10(8)spacecells/day) was orally administered for two weeks alongside intraperitoneal CTX injection (80spacemg/kg) on days 10, 11, and 12. Para-HY7017 attenuated CTX-induced colon shortening and preserved tight junction proteins ZO-1 (pspace<space0.05) and CLAUDIN-5 (pspace<space0.01). Fecal microbiota profiling revealed that Para-HY7017 mitigated CTX-induced dysbiosis by enriching short-chain fatty acid (SCFA)-producing genera, accompanied by elevated fecal acetate, propionate, and butyrate (pspace<space0.01, pspace<space0.05, and pspace<space0.01, respectively). Furthermore, CTX-induced reductions in serum IgA and IgG were substantially reversed by Para-HY7017 (pspace<space0.05 and pspace<space0.001, respectively), while live HY7017 additionally restored IgM levels (pspace<space0.05); TNF-alpha reductions were reversed in both groups (pspace<space0.05). Splenic immune function was also protected, with normalized apoptosis-related proteins (BAX/BCL-2 ratio, pspace<space0.01; CASPASE-3, pspace<space0.05) and reinstated Th1/Th2-linked transcription factors (T-BET and GATA-3, both pspace<space0.05) along with their downstream cytokines (Tnf,Ifng,Il1b, andIl4, pspace<space0.001, pspace<space0.01, pspace<space0.05, and pspace<space0.05, respectively). Collectively, Para-HY7017 and live HY7017 exerted distinct yet overlapping preventive effects, with Para-HY7017 showing particular advantages in butyrate-producing microbiota restoration and splenic Th1-associated cytokine responses. Gut microbiota modulation and SCFA production were strongly associated with improvements in intestinal barrier integrity and immune homeostasis, though causal confirmation awaits future mechanistic studies.

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