Objective. To investigate the effects of 5-hydroxytryptamine (5-HT) and intestinal flora on depression-like behavior induced by lead exposure in rats. Methods. 30 healthy SPF adult male SD rats were randomly divided into control group and lead exposure group. The depression-like behavior of rats was detected. The blood, striatum, and intestinal tissue were collected. The lead content was detected by ICP-MS. The mRNA expressions of ChgA, TPH1, 5-HT, and 5-HT3R were tested by qRT-PCR. The content of 5HT was checked by HPLC-ECD. The content of 5-HT3R was detected by ELISA. The protein expressions of 5-HT, 5-HT3R, ChgA, and TPH were gauged by immunohistochemistry. Fecal samples were collected, and the composition of intestinal flora in experimental rats was analyzed by 16 s RNA metagene sequencing. Results. Lead exposure can greatly cause depression. The content of 5-HT in blood and striatum in the lead exposure group decreased, and the expression levels of 5-HT, 5-HT3 R, ChgA, and TPH in the intestine decreased distinctly. Compared with the control group, the distribution of a-polymorphism related indexes Simpson, Chao1, Shannon, and ACE in rats with depressive-like behavior after lead exposure was significantly increased; in the lead exposure group, there were 61 different operational taxonomic units (OUTs) in intestinal flora at the family level. Based on linear discriminant analysis, it was found that the key bacteria were Lactobacillaceae and Bifidobacteriaceae, and their abundance decreased evidently in the lead exposure group. Conclusion. Lead exposure improves depressive-like behavior by affecting intestinal flora and regulating neurotransmitter 5-HT through the intestinal-brain axis.

The aim of this study was to observe the depression-like behavior changes of rats exposed to lead with or without probiotic intervention, and to investigate changes in the gut microbiota and fecal short-chain fatty acids (SCFAs) levels after lead exposure, and the possible functions of probiotics in this process. Material and Methods: Adult male Sprague Dawley rats were exposed to a 300 mg/l lead acetate solution for 24 weeks, with or without probiotic (freeze-dried powder containing Lactobacillus and Bifidobacterium: 6 billion live bacteria/2 g) intervention in weeks 17-24. The sucrose preference test (SPT), the forced swim test (FST), and the tail suspension test (TST) were preformed to study the depression-like behaviors of these rats. The alteration of rat gut microbiota induced by lead exposure was analyzed by 16S rRNA sequencing, and the levels of fecal SCFAs were detected using gas chromatography. Results: Neurobehavioral tests showed that lead exposure induced depression-like behavior in rats, including reduced sucrose preference in the SPT, and increased immobility times in the FST and the TST. Sequencing and gas chromatography showed that lead exposure changed the structure and the phylogenetic diversity of the gut microbiota, as well as significantly altered the levels of SCFAs. Moreover, the depression-like behaviors, and the changes in both gut microbiota and SCFAs, could be mitigated by probiotic intervention. Conclusions: Lead exposure not only changes the structure and diversity of the gut microbiome but also affects metabolic function. Probiotic intervention may be a novel initiative for the prevention and treatment of neurological damage following lead exposure.