[Explanation on modern mechanism of "for abdominal-diseases, Zusanli is indicated": acupuncture at Zusanli (ST36) regulates the brain-gut "neuro-immune axis" for the treatment of diarrhea-predominant irritable bowel syndrome].

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional intestinal disorder characterized by recurrent abdominal pain, diarrhea and altered defecation habits. It is frequently comorbid with psychological disorders such as anxiety and depression, which greatly impair the quality of life. Accumulating evidence demonstrates that the core pathological links of IBS-D involve disrupted brain-gut interaction and dysregulation of the brain-gut "neuro-immune axis", including visceral hypersensitivity, low-grade mucosal inflammation, impaired intestinal barrier function, gut microbiota dysbiosis and abnormal autonomic nerve modulation. Zusanli (ST36) is an essential acupoint for digestive disorders, and the ancient maxim "for abdominal-diseases, Zusanli is indicated" summarizes its prominent clinical value in abdominal ailments. Modern studies have verified that acupuncture at ST36 can remodel vagal-sympathetic balance via the peripheral afferent-central integration-autonomic efferent circuit, modulate central nociceptive and emotional processing, and exert regulatory effects on brain-gut peptide signals such as 5-hydroxytryptamine, suppress immune activation and release of inflammatory mediators, improve the expression of tight-junction proteins and intestinal mucosal permeability, as well as modulate microbiota-metabolite-related pathways. Thereby, it attenuates the neuro-immune feedback of "stress-inflammation-pain amplification", alleviates visceral hypersensitivity and relieves symptoms including abdominal pain and diarrhea. Taking the classical maxim "for abdominal-diseases, Zusanli is indicated" as a clue, this paper reviews research advances regarding acupuncture at ST36 in treating IBS-D by regulating the brain-gut "neuro-immune axis". Limitations of current evidence are also pointed out, including insufficient circuit verification, unclear stimulus parameter-effect relationship and non-standardized clinical protocols, so as to provide references for standardized application and mechanistic exploration of acupuncture at ST36 in treating functional gastrointestinal disorders.