{
  "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.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 34,
  "authors": [
    {
      "name": "Wen Zhao",
      "orcid": "0000-0002-0094-711X"
    },
    {
      "name": "Shaoqi Shi",
      "orcid": "0009-0007-1724-086X"
    },
    {
      "name": "Limian Zhou",
      "orcid": "0009-0004-0767-4961"
    },
    {
      "name": "Liang Zhao",
      "orcid": "0000-0001-9244-3121"
    },
    {
      "name": "Juan Chen"
    },
    {
      "name": "Yinghua Liu",
      "orcid": "0000-0003-2079-9991"
    },
    {
      "name": "Qi Zhang"
    },
    {
      "name": "Hao Zhang",
      "orcid": "0000-0002-7758-5161"
    },
    {
      "name": "Zhi Zhao"
    },
    {
      "name": "Chengying Zhang",
      "orcid": "0009-0000-4173-0753"
    },
    {
      "name": "Yixuan Li"
    },
    {
      "name": "Wei-Lian Hung"
    },
    {
      "name": "Rong Liu",
      "orcid": "0000-0002-1996-0015"
    },
    {
      "name": "Dekui Jin"
    },
    {
      "name": "Ming Zhang"
    },
    {
      "name": "Guang Li"
    },
    {
      "name": "Xinjuan Liu",
      "orcid": "0000-0001-7532-282X"
    },
    {
      "name": "Xiaoxia Li"
    },
    {
      "name": "Shaoyang Ge"
    },
    {
      "name": "Zhaozhong Zeng"
    },
    {
      "name": "Yong Zhang",
      "orcid": "0009-0007-3751-2615"
    },
    {
      "name": "Hanglian Lan"
    },
    {
      "name": "Qiuyue Jiang"
    },
    {
      "name": "Yanling Hao"
    },
    {
      "name": "Jie Guo",
      "orcid": "0000-0001-6104-9957"
    },
    {
      "name": "Huiyuan Guo",
      "orcid": "0000-0003-0792-177X"
    },
    {
      "name": "Yuyang Zhao",
      "orcid": "0000-0001-5644-9913"
    },
    {
      "name": "Wei Xiong"
    },
    {
      "name": "Xiaokang Niu",
      "orcid": "0009-0000-7111-6105"
    },
    {
      "name": "Liwei Zhang",
      "orcid": "0009-0000-4396-0966"
    },
    {
      "name": "Jian He",
      "orcid": "0009-0003-7881-4565"
    },
    {
      "name": "Jingjing He",
      "orcid": "0000-0002-2427-9064"
    },
    {
      "name": "Ran Wang",
      "orcid": "0000-0001-7125-5690"
    },
    {
      "name": "Fazheng Ren",
      "orcid": "0000-0002-5485-6862"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7376nsny0qnns.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77524-x",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737084/",
  "id": "7376nsny0qnns",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-77524-x",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2715|Gastrointestinal motility and disorders"
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  "openalex": "W7220678659",
  "pdf_url": "https://www.nature.com/articles/s41467-026-77524-x_reference.pdf",
  "pmcid": "PMC13737084",
  "pmid": "42982797",
  "published": "2026-10-06",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/7376nsny0qnns.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
      "native_id": "10.1038/s41467-026-77524-x",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-77524-x"
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      "first_seen": "2026-11-09T12:22:23Z",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2715|Gastrointestinal motility and disorders",
      "subfield": "general"
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  ],
  "title": "Bifidobacterium animalis subsp. lactis BL-99 ameliorates age-related intestinal hypomotility in older adults: a randomized controlled trial",
  "title_text": "Bifidobacterium animalis subsp. lactis BL-99 ameliorates age-related intestinal hypomotility in older adults: a randomized controlled trial",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:23Z",
  "url": "https://research.draconitic.com/paper/7376nsny0qnns",
  "venue": "Nature Communications",
  "versions": []
}