Exercise alleviated intestinal damage and microbial disturbances in mice exposed to fluoride

Gastrointestinal reaction is an important symptom of fluorosis and is associated with intestinal morphological and functional impairment. Regular moderate exercise may reduce the incidence of infection and contribute to the maintenance of intestinal mucosal function and immune homeostasis. In this study, the mice were randomly divided to four groups: control group (C, distilled water), exercise group (E, distilled water and treadmill exercise), fluoride group (F, 100 mg/L NaF), and exercise plus fluoride group (EF, 100 mg/L NaF and treadmill exercise). The treadmill exercise was performed as 5 m/min, 5 min; 10 or 12 m/min, 20 min; 5 m/min, 5 min, with 5 consecutive days per week. After 6 months, exercise alleviated the intestinal morphological structure damage and restored the villus height (VH) and VH/crypt depth (VH/CD) in the duodenum of fluoride-exposed mice. Exercise decreased the mRNA expressions of IL-1β, IL-6, TNF-α, TLR2 and NF-κB (p65) in fluoride-exposed mice, and restored the gene levels of Occludin and ZO-1 in the duodenum, as well as Occludin, ZO-1, and Claudin-1 in the colon. Although there were no significant differences in the Occludin and ZO-1 protein expressions between F and EF, two proteins in EF presented statistical homogeneousness when compared with the C. The 16S rDNA high-throughput sequencing found that exercise restored the variations in intestinal microbiota composition and the abundances of specific bacteria in fluoride-exposed mice, including increasing the abundances of Epsilonbacteraenta and Firmicutes, reducing the Bacteroidetes abundance at the phylum level, and restoring the abundances of 13 bacterial genera. In conclusion, exercise improved intestinal morphological structure damage in fluoride-exposed mice, inhibited the secretion of duodenal inflammatory factors, increased the expression of tight junctions, and alleviated the microbial disorder in mice caused by fluoride exposure for 6 months through actively regulating the composition of intestinal microorganisms and the abundance of specific bacteria.