Efficacy and mechanism of Bifidobacterium animalis subsp. lactis BL-99 in promoting age-related intestinal peristalsis in older adults (PRJCA042472)

Decay of smooth muscle contractility is one of major trigors of aging-related intestinal hypomotility, which imposes a substantial healthcare burden. Yet effective targeted therapy towards that is still unavailable. Here, we identified the probiotic Bifidobacterium animalis subsp. lactis BL-99 as a microbiota modulator that restores gut motility through bile acid (BA)-mediated rescue of smooth muscle contractile function. In a double-blind clinical trial and naturally aged mouse models, BL-99 intervention significantly reduced the whole-gut transit time and concurrently remodeled the gut microbiota. This suppressed bile salt hydrolase-expressing bacteria, which preserved conjugated BA pools, including taurochenodeoxycholic acid (TCDCA). Mechanistic investigations revealed that BL-99 activated the serum response factor(SRF)-myocardin (Myocd) transcriptional axis in colonic smooth muscle cells (SMCs), restoring contractile apparatus components (e.g., a-SMA, SM-MHC). Crucially, TCDCA administration recapitulated BL-99 regulation of intestinal SMC contractile protein expression by directly inhibiting the PI3K/AKT pathway. Our findings established a microbiota-BA-SMC signaling axis that ameliorates age-related intestinal hypomotility, positioning both BL-99 and TCDCA as precision therapeutic candidates targeting SMC-related dysmotility.