{"doi":"10.20517/mtod.2026.37","title":"Navigating gut-liver metabolic homeostasis: the role of the autonomic nervous system","abstract":"<jats:p>The frequent clinical co-occurrence of intestinal and hepatic disorders points to underlying bidirectional communication along the gut-liver axis. Existing research has primarily focused on metabolic and humoral interactions, including bile acid circulation and portal venous signaling, whereas the autonomic nervous system (ANS) has received comparatively limited attention as an integrative regulatory pathway. This review reframes the axis through a neural perspective, arguing that the ANS functions as a master coordinator of metabolic homeostasis, linking immune regulation, metabolic function, and gut microbiota activity into a unified neuro-immune-endocrine network. The sympathetic and parasympathetic branches, along with the enteric nervous system, modulate barrier integrity, immune cell trafficking, hepatic glucose and lipid metabolism, and microbial composition via neurotransmitter-mediated and receptor-dependent signaling pathways. Dysregulation of this autonomic circuitry disrupts metabolic balance and is implicated in the shared pathophysiology of conditions such as inflammatory bowel disease (IBD) and metabolic dysfunction-associated steatotic liver disease (MASLD). Conversely, neuromodulation strategies, particularly noninvasive vagus nerve stimulation, have demonstrated therapeutic potential in reducing inflammation and restoring metabolic balance. By positioning the ANS as one of the central regulators of gut-liver metabolic cross-talk, this review advances current mechanistic understanding of gut-liver comorbidities and highlights bioelectronic medicine as a promising therapeutic strategy for metabolic disorders. This perspective bridges neuroscience, gastroenterology, and hepatology, offering novel insights for the management of complex, multi-organ metabolic diseases.</jats:p>","journal":"Metabolism and Target Organ Damage","year":2026,"id":640920,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1666021,"name":"Jia-Li He","orcid":null,"position":1,"is_corresponding":false},{"id":1267573,"name":"Yue Cheng","orcid":"0000-0002-1598-0959","position":2,"is_corresponding":false},{"id":1666022,"name":"Si-Rui Yu","orcid":null,"position":3,"is_corresponding":false},{"id":1666023,"name":"Meng-Ni Zhang","orcid":null,"position":4,"is_corresponding":false},{"id":1445568,"name":"Mei Yang","orcid":"0009-0002-5795-5054","position":5,"is_corresponding":false},{"id":1125535,"name":"Kun Chen","orcid":"0000-0003-1162-6896","position":6,"is_corresponding":false},{"id":1666024,"name":"Ming-Yue Wu","orcid":"0009-0009-1285-2378","position":7,"is_corresponding":false},{"id":732560,"name":"Jin Chai","orcid":"0000-0002-4760-5811","position":8,"is_corresponding":false},{"id":1666020,"name":"Run Sun","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Navigating gut-liver metabolic homeostasis: the role of the autonomic nervous system","abstract":"<jats:p>The frequent clinical co-occurrence of intestinal and hepatic disorders points to underlying bidirectional communication along the gut-liver axis. Existing research has primarily focused on metabolic and humoral interactions, including bile acid circulation and portal venous signaling, whereas the autonomic nervous system (ANS) has received comparatively limited attention as an integrative regulatory pathway. This review reframes the axis through a neural perspective, arguing that the ANS functions as a master coordinator of metabolic homeostasis, linking immune regulation, metabolic function, and gut microbiota activity into a unified neuro-immune-endocrine network. The sympathetic and parasympathetic branches, along with the enteric nervous system, modulate barrier integrity, immune cell trafficking, hepatic glucose and lipid metabolism, and microbial composition via neurotransmitter-mediated and receptor-dependent signaling pathways. Dysregulation of this autonomic circuitry disrupts metabolic balance and is implicated in the shared pathophysiology of conditions such as inflammatory bowel disease (IBD) and metabolic dysfunction-associated steatotic liver disease (MASLD). Conversely, neuromodulation strategies, particularly noninvasive vagus nerve stimulation, have demonstrated therapeutic potential in reducing inflammation and restoring metabolic balance. By positioning the ANS as one of the central regulators of gut-liver metabolic cross-talk, this review advances current mechanistic understanding of gut-liver comorbidities and highlights bioelectronic medicine as a promising therapeutic strategy for metabolic disorders. This perspective bridges neuroscience, gastroenterology, and hepatology, offering novel insights for the management of complex, multi-organ metabolic diseases.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19767382","pmcid":null,"openalex_id":"https://openalex.org/W7163814372","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.73158347,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://f.oaes.cc/xmlpdf/published/article/bf6048df586767a69ac1aa86d24ec52d/mtod6037.pdf","host_type":"journal"},{"url":"https://f.oaes.cc/xmlpdf/published/article/bf6048df586767a69ac1aa86d24ec52d/mtod6037.pdf","host_type":"publisher"},{"url":"https://www.oaepublish.com/articles/mtod.2026.37","host_type":"publisher"},{"url":"https://doi.org/10.20517/mtod.2026.37","host_type":"journal"}],"fields_of_study":["Vagus Nerve Stimulation Research","Gastrointestinal motility and disorders","Heart Rate Variability and Autonomic Control"],"mesh_terms":[],"keywords":["Enteric nervous system","Autonomic nervous system","Parasympathetic nervous system","Neuromodulation","Vagus nerve","Immune system","Central nervous system","Inflammation","Disease"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T14:26:23.721578Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}