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Organophosphorus pesticide chlorpyrifos intake promotes obesity and insulin resistance through impacting gut and gut microbiota.

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PubMed ID: 30744700

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Liang Y, Zhan J, Liu D, Luo M, Han J, Liu X, Liu C, Cheng Z, Zhou Z, Wang P

Microbiome. Feb 2019. doi: 10.1186/s40168-019-0635-4

COMMENT: This work investigates the effects of a widely used pesticide on gut microbiota and obesity. Previous studies have detected this pesticide in food, and have found that in animals can develop obesity and other disorders. In this study, the gut microbiota of two strains of mice that simulate different dietary patterns was analyzed by 16S rRNA sequencing (V4-V5 region) to determine chlorpyrifos-induced change in gut microbiota composition.

Objective

The main goal of this study was to identify new mechanisms by which pesticides affect humans, so that the information obtained can be used for more comprehensive assessment of the chronic health risks of pesticide exposure. To this end, we fed C57Bl/6 and CD-1 (ICR) mice a high-fat diet (HFD) or normal-fat diet (NFD) and investigated if chlorpyrifos could induce insulin resistance (IR) and obesity through the above-mentioned pathways

Main results

The results showed that chlorpyrifos altered the microbiota composition and compromised the integrity of the gut barrier, which induced IR and obesity by upregulating inflammatory pathways. 

A high-fat diet (HFD) decreased Bacteroidetes and increased Firmicutes, which are typical HFD-induced change in gut microbiota and related to obesity

Gut microbiota in mice fed HFD was not significantly affected by chlorpyrifos treatment. A possible explanation is that the gut microbiota can be affected by HFD dominantly (…), compared with which the impact of chlorpyrifos was limited.  

The analysis was focused on the effects of chlorpyrifos on microbiota composition in mice fed normal-fat diet (NFD). In both C57Bl/6 and CD-1 (ICR) mice fed NFD, chlorpyrifos treatment resulted in an increase in Proteobacteria phyla and a decrease in Bacteroidetes phyla.

To investigate the effects of chlorpyrifos-altered microbiota, half of the mice in NCPF group (normal-fat diet + chlorpyrifos)  were treated with antibiotics after 8-week chlorpyrifos treatment. The results showed that chlorpyrifos-led obesity and IR were completely restored by antibiotic treatment for 4 weeks, suggesting that gut bacteria were involved in chlorpyrifos-induced obesity and IR. In addition, the results of microbiota transplantation experiment using NCPF and NFD groups’ microbiota showed that chlorpyrifos-altered microbiota could also induce obesity and IR, especially in NFD-fed C57Bl/6 mice. 

Conclusions

In this study, we found that chlorpyrifos impaired intestinal integrity to promote more lipopolysaccharides (LPS) entry into the body resulting in low-grade inflammation, which ultimately led to insuline resistance (IR) and obesity.

The results of antibiotic treatment and microbiota transplantation experiments showed that chlorpyrifos-altered microbiota were involved in chlorpyrifos-induced obesity and IR.

Contributor

Diana López-Farfán