Changes in Gut Microbiota May Be Early Signs of Liver Toxicity Induced by Epoxiconazole in Rats

Abstract

Objective: The gut microbiome is essential for human health due to its effects on disease development, drug metabolism and the immune system. It may also play a role in the interaction with environmental toxicants. However, the effect of epoxiconazole, a fungicide active ingredient from the class of azoles developed to protect crops, on the abundance and composition of the gut microbiome has never been studied. We put forward the hypothesis that changes in gut microbiota may be early signs of toxicity induced by epoxiconazole. Methods: In this study, female rats were fed with epoxiconazole-adulterated diets (0, 4 and 100 mg/kg/day) for 90 days. The gut microbiome was determined by 16S rRNA gene sequencing. Body and organ weight, and blood biochemistry were also measured after 90 days of oral epoxiconazole exposure. Results: Interestingly, the abundance of gut Firmicutes decreased, and Bacteroidetes and Proteobacteria increased. At family level, Lachnospiraceae and Enterobacteriaceae were selectively enriched following epoxiconazole exposure. Our results indicate that epoxiconazole exposure may induce changes in the gut microbiome and potential liver toxicity. Conclusion: Changes in the gut microbiome may be used as early indicators for monitoring the health risk of the host.

Bidirectional interactions between indomethacin and the murine intestinal microbiota

“…A decrease of S24-7 , a family of Bacteroidetes, such as induced here by indomethacin, has been observed in a mouse model of colorectal cancer ( Liang et al, 2014 ) and in mice with high fat diet-induced obesity ( Evans et al, 2014 ). Lachnospiraceae , also increased following indomethacin administration, have been associated with lupus ( Zhang et al, 2014 ), drug-induced liver toxicity ( Xu et al, 2015 ) and the development of obesity and diabetes in genetically susceptible mice ( Kameyama and Itoh, 2014 ). While the importance of many of these observations remains to be established, they do suggest possible mechanisms of adverse health consequences.…”

Microbiome-Aware Ecotoxicology of Organisms: Relevance, Pitfalls, and Challenges

“…Alternatively, xenobiotics can also alter activities of the gut microbiome (23). Besides the obvious example of antibiotics, many molecules such as epoxiconazole or glyphosate, both pesticides, are known to induce shifts in microbiome compositions (32). Because the microbiome substantially responds and interacts with contaminants, it must now be considered a key player in toxicology.…”

The Role of the Human Microbiome in Chemical Toxicity

“…139 Not only can their data be used to predict which zebrafish will be susceptible to triclosan based on their gut microbiome, but it could also discriminate whether or not an individual had been exposed. Another group reported changes in the abundance of certain phyla of bacteria following epoxiconazole exposure 140 and suggest that these changes could be used as early indicators of toxic exposure and potentially for predicting health risk to the host. 140 The explosion of recent work looking for toxic exposureinduced changes in the microbiome is a reaction to concerns of the microbiome in human health, but more importantly, it indicates that TMM is likely to be a broader effect than has previously been observed.…”

“…Another group reported changes in the abundance of certain phyla of bacteria following epoxiconazole exposure 140 and suggest that these changes could be used as early indicators of toxic exposure and potentially for predicting health risk to the host. 140 The explosion of recent work looking for toxic exposureinduced changes in the microbiome is a reaction to concerns of the microbiome in human health, but more importantly, it indicates that TMM is likely to be a broader effect than has previously been observed. The effects of toxicants on bacteria and other microbes have been well studied outside an animal host.…”

“…Another group reported changes in the abundance of certain phyla of bacteria following epoxiconazole exposure 140 and suggest that these changes could be used as early indicators of toxic exposure and potentially for predicting health risk to the host. 140…”