Microplastics perturb colonic epithelial homeostasis associated with intestinal overproliferation, exacerbating the severity of colitis.

A great amount of the population died due to living or working in an unhealthy environment, highlighting the critical role of environmental pollutants in inducing diseases. Microplastics are widespread environmental pollutants and have been found in various tissues of human beings, yet the risk of microplastics in the occurrence of disease, especially environmentally-related colitis, is unclear. This study focused on the effects of microplastics exposure on intestinal homeostasis and the initiation of colitis. We noticed that microplastics exposure had a limited impact on mice, as verified by no difference observed in bodyweight change, IL-1β and IL-6 levels in jejunum and liver. Nevertheless, in the colon, the IL-1β and IL-6 levels were slightly increased and the goblet cell number was decreased. Interestingly, we observed that crypt number and depth, the levels of intestinal stem cell markers, combined with the expression of proliferating cell nuclear antigen and proto-oncogene c-Myc were all significantly increased with microplastics treatment, indicating the overproliferation of colonic mucosa. The effect of microplastics on proliferation and differentiation of crypt was further demonstrated to be regulated by the overactivation of the Notch signaling pathway in intestinal organoids. Furthermore, microplastics exposure accelerated the development of colitis with severe bodyweight loss, diarrhea and bloody stools, macroscopic and pathological damage, and inflammation levels. Worsened liver pathological damage and inflammation in mice with colitis under microplastics exposure also were found. These results suggested that microplastics disrupted the balance between colonic epithelium self-renewal and differentiation, exacerbating the colitis, and might be an environmental-related disease risk factor.