In summary, our current study demonstrates that the probiotic C. butyricum ameliorates PNS inflammation by regulating Th17/Tregs balance through the HO-1/STAT3/RORγt signaling pathway and reshaping gut/urine microbiota in the gut-kidney axis, which may be a safe and inexpensive treatment for PNS. The gene discussed is HMOX1; the disease is paraneoplastic neurologic syndrome.