Exploration of the Mechanism of the Method of Warming and Tonifying the Spleen and Kidney in Treating Diarrhea-predominant Irritable Bowel Syndrome Based on the “Brain-Gut Axis” Theory

In the treatment of IBS-D, TCM commonly employs prescriptions that warm and tonify the spleen and kidney to address IBS-D cases characterized by spleen-kidney yang deficiency. These include the Changkang Formula, Tongxie Sishen Decoction, Wenshen Jianpi Guchang Formula, Jiuxie Formula, Wenshen Jianpi Formula, and Wenshen Jianpi Decoction. The compositions of these formulas are mainly based on modifications of the Sishen Pill. The TCM approach of warming and tonifying the spleen and kidney can suppress the expression levels of 5-HT and SP in the serum and colon tissues of rat models with spleen-kidney yang deficiency. Additionally, it can elevate the levels of GAS, CORT, and ACTH in the serum. This approach can regulate the p38 MAPK/JNK signaling pathway and downregulate the expression of the c-Fos gene in the colon tissues, dorsal root ganglia, and hippocampal tissues of IBS-D rat models. By doing so, it can modulate the brain-gut axis function and alleviate the symptoms of IBS-D in rat models with spleen-kidney yang deficiency. In the context of treating patients, the TCM method of warming and tonifying the spleen and kidney can also reduce the levels of BDNF, NPY, GAS, 5-HT, CGRP, VIP, SST, D-lactic acid, DAO, and SP in the serum of IBS-D patients with spleen-kidney yang deficiency. It can downregulate the expression of TrkB, BDNF, and CGRP in patients and increase the levels of motilin and NO in the serum. Through these mechanisms, it can regulate the brain-gut axis function, alleviate visceral hypersensitivity in IBS-D patients, improve the inflammatory response, and enhance the colonic barrier function, thereby alleviating clinical symptoms such as diarrhea and abdominal pain in IBS-D patients. Evidently, the monomers and compound formulas of TCM for warming and tonifying the spleen and kidney can alter the content of brain-gut peptides. The regulation of the “gut-brain axis” in the treatment of IBS-D has demonstrated effectiveness.