Simotang Alleviates the Gastrointestinal Side Effects of Chemotherapy by Altering Gut Microbiota

Abstract

Chemotherapy is one of the three most commonly used methods for treatment of malignant tumors. Though chemotherapy is effective in killing cancer cells and preventing cancer from invasion and metastasis, patients receiving chemotherapy might also face various side effects. The toxicity and side effects caused by chemotherapy drugs are mostly gastrointestinal reactions, of which gastrointestinal mucositis is the most common The clinical manifestations of gastrointestinal mucositis include nausea, anorexia, vomiting, ulcers, abdominal pain, abdominal distension, diarrhea, constipation, and infection and could seriously affect daily life and even hinder the process of normal treatment of cancer patients. Therefore, drugs that are used to treat gastrointestinal mucositis are also used during cancer treatment to alleviate chemotherapy gastrointestinal side effects. Nowadays, the most commonly used anti-gastrointestinal side-effect drugs in clinical a clinical setting are antiemetics, with some examples being 5-hydroxytryptamine (5-HT) receptor antagonists (e.g., palonosetron), neurokinin (NK) 1 receptor antagonists (e.g., aprepitant), corticosteroids (e.g., dexamethasone) and dopamine (DA) D2 receptor antagonists (e.g., metoclopramide). However, these drugs might also be accompanied by side effects, for example, palonosetron might induce headaches and constipation Aprepitant might cause headache, fatigue, neutropenia, constipation, and pruritus Dexamethasone might bring about glucose tolerance alteration, behavioral and mood changes And metoclopramide could lead to tardive dyskinesia, drowsiness and acute dystonic reaction Meanwhile, nutrition therapy can relieve the gastrointestinal side effects of patients Simotang oral liquid (SMT) is a traditional Chinese medicine (TCM) consisting of four natural plants and is used to alleviate gastrointestinal side effects after chemotherapy and functional dyspepsia (FD). However, the mechanism by which SMT helps cure these gastrointestinal diseases is still unknown. Here, we discovered that SMT could alleviate gastrointestinal side effects after chemotherapy by altering gut microbiota. C57BL/6J mice were treated with cisplatin (DDP) and SMT, and biological samples were collected. Pathological changes in the small intestine were observed, and the intestinal injury score was assessed. The expression levels of the inflammatory factors IL-1 and IL-6 and the adhesive factors Occludin and ZO-1 in mouse blood or small intestine tissue were also detected. Moreover, the gut microbiota was analyzed by high-throughput sequencing of 16S rRNA amplicons. SMT was found to effectively reduce gastrointestinal mucositis after DDP injection, which lowered inflammation and tightened the intestinal epithelial cells. Gut microbiota analysis showed that the abundance of the anti-inflammatory microbiota was downregulated and that the inflammatory microbiota was upregulated in DDP-treated mice. SMT upregulated antiinflammatory and anticancer microbiota abundance, while the inflammatory microbiota was downregulated. An antibiotic cocktail (ABX) was also used to delete mice gut microbiota to test the importance of gut microbiota, and we found that SMT could not alleviate gastrointestinal mucositis after DDP injection, showing that gut microbiota might be an important mediator of SMT treatment. Our study provides evidence that SMT might moderate gastrointestinal mucositis after chemotherapy by altering gut microbiota.

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