Electromagnetic field exposure-induced depression features could be alleviated by heat acclimation based on remodeling the gut microbiota

Background: Electromagnetic pollution cannot be ignored. Long-term low-dose electromagnetic field (EMF) exposure can cause central nervous system dysfunction without effective prevention. Materials/Methods: Male C57BL/6J mice (6-8 weeks, 17-20 g) were used in this study. Depression-like and anxiety-like behaviors detected by behavioral experiments were compared among different treatments. 16S rRNA gene sequencing and non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics were used to explore the relationship between EMF exposure and heat acclimation (HA) effects on gut microbes and serum metabolites. Results: Both EMF and HA regulated the proportions of p_Firmicutes and p_Bacteroidota. EMF exposure caused the proportions of 6 kinds of bacteria, such as g_Butyricicoccus and g_Anaerotruncus, to change significantly (p < 0.05). HA restored the balance of gut microbes that was affected by EMF exposure and the proportion of probiotics (g_Lactobacillus) increased significantly (p < 0.01). Serum metabolite analysis suggested that HA alleviated the disturbance of serum metabolites (such as cholesterol and D-mannose) induced by EMF exposure. Both the metabolic KEGG pathways and PICRUSt functional analysis demonstrated that tryptophan metabolism, pyrimidine metabolism and amino acid biosynthesis were involved. Conclusions: EMF exposure not only led to depression-like neurobehavioral disorders, but also to gut microbiota imbalance. HA alleviated the depression features caused by EMF exposure. Based on the analysis of gut microbiota associated with serum metabolites, we speculated that gut microbiota might play a vital role in the cross-tolerance provided by HA.