Dataset Information

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

ABSTRACT:

Background

Disruption of the gut microbiota homeostasis may induce low-grade inflammation leading to obesity-associated diseases. A major protective mechanism is to use the multi-layered mucus structures to keep a safe distance between gut epithelial cells and microbiota. To investigate whether pesticides would induce insulin resistance/obesity through interfering with mucus-bacterial interactions, we conducted a study to determine how long-term exposure to chlorpyrifos affected C57Bl/6 and CD-1 (ICR) mice fed high- or normal-fat diets. To further investigate the effects of chlorpyrifos-altered microbiota, antibiotic treatment and microbiota transplantation experiments were conducted.

Results

The results showed that chlorpyrifos caused broken integrity of the gut barrier, leading to increased lipopolysaccharide entry into the body and finally low-grade inflammation, while genetic background and diet pattern have limited influence on the chlorpyrifos-induced results. Moreover, the mice given chlorpyrifos-altered microbiota had gained more fat and lower insulin sensitivity.

Conclusions

Our results suggest that widespread use of pesticides may contribute to the worldwide epidemic of inflammation-related diseases.

SUBMITTER: Liang Y

PROVIDER: S-EPMC6371608 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Liang Yiran Y Zhan Jing J Liu Donghui D Luo Mai M Han Jiajun J Liu Xueke X Liu Chang C Cheng Zheng Z Zhou Zhiqiang Z Wang Peng P

Microbiome 20190211 1

<h4>Background</h4>Disruption of the gut microbiota homeostasis may induce low-grade inflammation leading to obesity-associated diseases. A major protective mechanism is to use the multi-layered mucus structures to keep a safe distance between gut epithelial cells and microbiota. To investigate whether pesticides would induce insulin resistance/obesity through interfering with mucus-bacterial interactions, we conducted a study to determine how long-term exposure to chlorpyrifos affected C57Bl/6 ...[more]

PMID: 30744700

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Project description:BackgroundObesity is a risk factor for colorectal cancer (CRC). The role of gut microbiota in mediating the cancer-promoting effect of obesity is unknown.MethodsAzoxymethane (AOM)-treated, ApcMin/+ and germ-free mice were gavaged with feces from obese individuals and control subjects respectively. The colonic tumor load and number were recorded at the endpoint in two carcinogenic models. The gut microbiota composition and colonic transcriptome were assessed by metagenomic sequencing and RNA sequencing, respectively. The anticancer effects of bacteria depleted in fecal samples of obese individuals were validated.FindingsConventional AOM-treated and ApcMin/+ mice receiving feces from obese individuals showed significantly increased colon tumor formation compared with those receiving feces from control subjects. AOM-treated mice receiving feces from obese individuals showed impaired intestinal barrier function and significant upregulation of pro-inflammatory cytokines and activation of oncogenic Wnt signaling pathway. Consistently, transferring feces from obese individuals to germ-free mice led to increased colonic cell proliferation, intestinal barrier function impairment, and induction of oncogenic and proinflammatory gene expression. Moreover, germ-free mice transplanted with feces from obese human donors had increased abundance of potential pathobiont Alistipes finegoldii, and reduced abundance of commensals Bacteroides vulgatus and Akkermansia muciniphila compared with those receiving feces from human donors with normal body mass index (BMI). Validation experiments showed that B. vulgatus and A. muciniphila demonstrated anti-proliferative effects in CRC, while A. finegoldii promoted CRC tumor growth.InterpretationOur results supported the role of obesity-associated microbiota in colorectal carcinogenesis and identified putative bacterial candidates that may mediate its mechanisms. Microbiota modulation in obese individuals may provide new approaches to prevent or treat obesity-related cancers including CRC.FundingThis work was funded by National Key Research and Development Program of China (2020YFA0509200/2020YFA0509203), National Natural Science Foundation of China (81922082), RGC Theme-based Research Scheme Hong Kong (T21-705/20-N), RGC Research Impact Fund Hong Kong (R4632-21F), RGC-CRF Hong Kong (C4039-19GF and C7065-18GF), RGC-GRF Hong Kong (14110819, 14111621), and NTU Start-Up Grant (021337-00001).

Dataset Information

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

Background

Results

Conclusions

Publications

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

Similar Datasets

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