Suo Quan Wan alleviates hypoxia-induced bladder hypersensitivity via the gut microbiota-brain axis

Chronic intermittent hypoxia (CIH) is strongly associated with nocturnal enuresis (NE). Suo Quan Wan (SQW) is a traditional herbal formula used to treat enuresis. This study aimed to investigate the therapeutic effect of SQW on CIH-induced bladder dysfunction and elucidate the mechanism involving the microbiota-gut-brain axis. C57BL/6 mice were divided into four groups: a normoxic Control group, and three CIH-exposed groups treated with PBS (Enuresis-Like, EL group), SQW (SQW group), or SQW plus an antibiotic cocktail (SQW+ABX group). Bladder function was assessed via voiding spot assays and urodynamics. We evaluated intestinal barrier integrity (Occludin, serum LPS), systemic stress hormones (ACTH, corticosterone, aldosterone), and hypothalamic CRH neuron activity. The EL group exhibited urinary frequency and bladder hypersensitivity (lowered voiding threshold), alongside compromised intestinal barriers, elevated systemic stress hormones, and hypothalamic hyperactivity. SQW treatment significantly reversed bladder hypersensitivity, restored gut barrier function, normalized hormone levels, and suppressed hypothalamic activation. Critically, antibiotic co-treatment abrogated all therapeutic effects of SQW. SQW alleviates CIH-induced bladder hypersensitivity by restoring intestinal barrier integrity, thereby attenuating the systemic endocrine stress response and suppressing central hypothalamic hyperactivity. These effects are fundamentally dependent on the gut microbiota. Our findings identify the microbiota-gut-brain axis as a key therapeutic target for SQW in treating functional bladder disorders associated with hypoxia.