Bifidobacterium animalis subsp. lactis BL-99 ameliorates age-related intestinal hypomotility in older adults: a randomized controlled trial
Abstract
The decay of smooth muscle contractility is a major trigger of aging-related intestinal hypomotility, which imposes a substantial healthcare burden. Despite this, effective targeted therapy for this condition remains unavailable. Here, we identified the probiotic Bifidobacterium animalis subsp. lactis BL-99 as a microbiota modulator that restores gut motility through the bile acid (BA)-mediated rescue of smooth muscle contractile function. In a randomized, double-blind clinical trial (ChiCTR2300077583, with the primary endpoint of whole-gut transit time [WGTT], and secondary endpoints including bowel movement frequency, symptom severity, and quality-of-life measures) and naturally aged mouse models, BL-99 intervention significantly reduced the WGTT 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 was associated with enhanced expression of the serum response factor (SRF)–myocardin (Myocd) transcriptional axis in colonic smooth muscle cells (SMCs), restoring contractile apparatus components (e.g., α-SMA, SM-MHC). Crucially, TCDCA administration recapitulated BL-99 regulation of intestinal SMC contractile protein expression by 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.
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BibTeX
@article{zhao2026bifidobacterium,
title = {{Bifidobacterium animalis subsp. lactis BL-99 ameliorates age-related intestinal hypomotility in older adults: a randomized controlled trial}},
author = {Wen Zhao and Shaoqi Shi and Limian Zhou and Liang Zhao and Juan Chen and Yinghua Liu and Qi Zhang and Hao Zhang and Zhi Zhao and Chengying Zhang and Yixuan Li and Wei-Lian Hung and Rong Liu and Dekui Jin and Ming Zhang and Guang Li and Xinjuan Liu and Xiaoxia Li and Shaoyang Ge and Zhaozhong Zeng and Yong Zhang and Hanglian Lan and Qiuyue Jiang and Yanling Hao and Jie Guo and Huiyuan Guo and Yuyang Zhao and Wei Xiong and Xiaokang Niu and Liwei Zhang and Jian He and Jingjing He and Ran Wang and Fazheng Ren},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-77524-x},
url = {https://www.nature.com/articles/s41467-026-77524-x},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Bifidobacterium animalis subsp. lactis BL-99 ameliorates age-related intestinal hypomotility in older adults: a randomized controlled trial
AU - Wen Zhao
AU - Shaoqi Shi
AU - Limian Zhou
AU - Liang Zhao
AU - Juan Chen
AU - Yinghua Liu
AU - Qi Zhang
AU - Hao Zhang
AU - Zhi Zhao
AU - Chengying Zhang
AU - Yixuan Li
AU - Wei-Lian Hung
AU - Rong Liu
AU - Dekui Jin
AU - Ming Zhang
AU - Guang Li
AU - Xinjuan Liu
AU - Xiaoxia Li
AU - Shaoyang Ge
AU - Zhaozhong Zeng
AU - Yong Zhang
AU - Hanglian Lan
AU - Qiuyue Jiang
AU - Yanling Hao
AU - Jie Guo
AU - Huiyuan Guo
AU - Yuyang Zhao
AU - Wei Xiong
AU - Xiaokang Niu
AU - Liwei Zhang
AU - Jian He
AU - Jingjing He
AU - Ran Wang
AU - Fazheng Ren
PY - 2026
DA - 2026/10/06
JO - Nature Communications
DO - 10.1038/s41467-026-77524-x
UR - https://www.nature.com/articles/s41467-026-77524-x
AB - The decay of smooth muscle contractility is a major trigger of aging-related intestinal hypomotility, which imposes a substantial healthcare burden. Despite this, effective targeted therapy for this condition remains unavailable. Here, we identified the probiotic Bifidobacterium animalis subsp. lactis BL-99 as a microbiota modulator that restores gut motility through the bile acid (BA)-mediated rescue of smooth muscle contractile function. In a randomized, double-blind clinical trial (ChiCTR2300077583, with the primary endpoint of whole-gut transit time [WGTT], and secondary endpoints including bowel movement frequency, symptom severity, and quality-of-life measures) and naturally aged mouse models, BL-99 intervention significantly reduced the WGTT 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 was associated with enhanced expression of the serum response factor (SRF)–myocardin (Myocd) transcriptional axis in colonic smooth muscle cells (SMCs), restoring contractile apparatus components (e.g., α-SMA, SM-MHC). Crucially, TCDCA administration recapitulated BL-99 regulation of intestinal SMC contractile protein expression by 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.
SN - 2041-1723
ER -