{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:04:38Z","timestamp":1780653878597,"version":"3.54.1"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The vagus nerve (innervating the gut from esophagus to proximal colon) and sacral nerve (innervating distal colon and rectum) are key parasympathetic regulators of gastrointestinal (GI) function. While vagus nerve stimulation (VNS) has shown therapeutic potential in upper GI disorders, its role in modulating distal colon and rectal function remains poorly understood. This study investigated the effects and mechanisms of VNS on distal colon transit and rectal tone in rats. Adult male Sprague Dawley rats were implanted with stimulation electrodes at the cervical or auricular vagal afferent nerve. VNS was applied with varying frequencies, pulse widths, and amplitudes. Rectal tone was assessed using a barostat device, and distal colon transit was evaluated using bead expulsion. Nitrergic and cholinergic contributions were examined using L-NAME and nNOS expression, and acetylcholine ELISA and ChAT expression, respectively. Central pathways were investigated by immunofluorescence staining of c-fos and ChAT in the nucleus tractus solitarius (NTS). Sacral efferent pathway was assessed by chemogenetic inhibition of the dorsal motor nucleus of the vagus (DMV) and Barrington nucleus (BN\/PMC). VNS (5 Hz, 0.1 and 0.5 ms, 0.5 mA) significantly increased rectal volume, indicating relaxation, and accelerated distal colon transit. L-NAME abolished VNS-induced rectal relaxation, while nNOS expression in the rectum was upregulated, confirming nitrergic mediation. Distal colon transit was associated with increased acetylcholine release and ChAT expression, highlighting cholinergic involvement. VNS enhanced c-fos and ChAT-positive neurons in the NTS, suggesting central integration of vagal afferent signals. Chemogenetic inhibition of DMV and BN attenuated rectal relaxation, indicating that VNS effects are mediated via a vagal\u2013NTS\u2013sacral pathway. VNS modulates distal colon transit and rectal tone through coordinated nitrergic and cholinergic signaling and central vagal-to-sacral circuits. These findings reveal functional crosstalk between vagal and sacral parasympathetic pathways and provide mechanistic insight into potential VNS therapy for lower GI disorders.<\/jats:p>","DOI":"10.3390\/cells15111037","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:43:04Z","timestamp":1780648984000},"page":"1037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Vagal Nerve Stimulation on Rectal Tone and Distal Colon Transit in Rats Mediated via the Vagal-Sacral Pathway"],"prefix":"10.3390","volume":"15","author":[{"given":"Yan","family":"Li","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijie","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahangir","family":"Alam","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3783-7610","authenticated-orcid":false,"given":"Shiyuan","family":"Gong","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0191-5697","authenticated-orcid":false,"given":"Jiande D. 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