Fishman comments: Methotrexate is a commonly used drug to treat various ocular autoimmune conditions including uveitis and scleritis. Unfortunately, GI side effects are a problem. This is a nice paper exploring the possibility of reducing GI toxicity by increasing the protective intestinal microbiota. Hopefully, we will continue to understand the microbiome better to reduce our dependence on toxic immune modulating drugs
Authors: Duozhuang Tang, Ting Zeng, Yiting Wang, Hui Cui, Jianying Wu, Bing Zou, Zhendong Tao, Liu Zhang, George B. Garside & Si Tao (2020) Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity, Gut Microbes, DOI: 10.1080/19490976.2020.1714401
Methotrexate (MTX) is a typical chemotherapeutic drug that is widely used in the treatment of various malignant diseases as well as autoimmune diseases, with gastrointestinal toxicity being its most prominent complication which could have a significant effect on the prognosis of patients. Yet effective ways to alleviate such complications remains to be explored. Here we show that 30% dietary restriction (DR) for 2 weeks dramatically increased the survival rate of 2-month-old female mice after lethal-dose MTX exposure. DR significantly reduced intestinal inflammation, preserved the number of basal crypt PCNA-positive cells, and protected the function of intestinal stem cells (ISCs) after MTX treatment. Furthermore, ablating intestinal microbiota by broad-spectrum antibiotics completely eliminated the protective effect achieved by DR. 16S rRNA gene deep-sequencing analysis revealed that short-term DR significantly increased the Lactobacillus genus, with Lactobacillus rhamnosus GG gavage partially mimicking the rescue effect of DR on the intestines of ad libitum fed mice exposed to lethal-dose MTX. Together, the current study reveals that DR could be a highly effective way to alleviate the lethal injury in the intestine after high-dose MTX treatment, which is functionally mediated by increasing the protective intestinal microbiota taxa in mice.