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Genome Biol. 2017 Jan 24;18(1):8. doi: 10.1186/s13059-016-1134-6.

Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis.

Author information

1
Department of Molecular Biology, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625021, India. oomvel@gmail.com.
2
Center for Molecular and Translational Medicine, Research Science Center, Georgia State University, Atlanta, GA, 30303, USA.
3
KMCH Research Foundation, Kovai Medical Centre and Hospital, Coimbatore, Tamil Nadu, 641014, India.
4
Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, 69372, France.
5
Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625021, India.
6
Department of Immunology, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625021, India.
7
Department of Molecular Biology, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625021, India.
8
Deparment of Zoology, Madras Christian College, Chennai, Tamil Nadu, 600059, India.
9
Department of Biochemistry, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625021, India.
10
Department of Microbial Technology, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625021, India.
11
Laboratory of Gene Regulation and Development, Program in Cellular Regulation and Development, National Institute of Child Health and Human Development, NIH, Bethesda, MD, 20892, USA.
12
Institute of Diabetes & Endocrinology, Alpha Hospital and Research Centre, Madurai, Tamil Nadu, 625009, India.
13
NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and Imperial College, London, UK.
14
Department of Molecular Biology, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625021, India. subbiahr@nrcbsmku.org.

Abstract

BACKGROUND:

Organophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature. Gut microbes were shown to degrade organophosphates and cause intestinal dysfunction. The diabetogenic nature of organophosphates was recently reported but the underlying molecular mechanism is unclear. We aimed to understand the role of gut microbiota in organophosphate-induced hyperglycemia and to unravel the molecular mechanism behind this process.

RESULTS:

Here we demonstrate a high prevalence of diabetes among people directly exposed to organophosphates in rural India (n = 3080). Correlation and linear regression analysis reveal a strong association between plasma organophosphate residues and HbA1c but no association with acetylcholine esterase was noticed. Chronic treatment of mice with organophosphate for 180 days confirms the induction of glucose intolerance with no significant change in acetylcholine esterase. Further fecal transplantation and culture transplantation experiments confirm the involvement of gut microbiota in organophosphate-induced glucose intolerance. Intestinal metatranscriptomic and host metabolomic analyses reveal that gut microbial organophosphate degradation produces short chain fatty acids like acetic acid, which induces gluconeogenesis and thereby accounts for glucose intolerance. Plasma organophosphate residues are positively correlated with fecal esterase activity and acetate level of human diabetes.

CONCLUSION:

Collectively, our results implicate gluconeogenesis as the key mechanism behind organophosphate-induced hyperglycemia, mediated by the organophosphate-degrading potential of gut microbiota. This study reveals the gut microbiome-mediated diabetogenic nature of organophosphates and hence that the usage of these insecticides should be reconsidered.

KEYWORDS:

Acetic acid; Diabetes; Fecal transplantation; Gluconeogenesis; Glucose intolerance; Gut microbiota; Metabolomics; Metatranscriptomics; Organophosphates

PMID:
28115022
PMCID:
PMC5260025
DOI:
10.1186/s13059-016-1134-6
[Indexed for MEDLINE]
Free PMC Article

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