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

Autor: Yacob Jenifer Christy, Leishman John Thumburaj, Ayothi Parthasarathy, Jeyaprakash Rajendhran, Albert Abhishek, Boominathan Meganathan, Varadaraj Vasudevan, Shanavas Syed Mohamed Puhari, D.D. Venkatesh Babu, Muthuirulan Pushpanathan, Gilles Mithieux, Allen J. Freddy, Kannan Suganya, Tharmarajan Ramprasath, Rajamani Koushick Rajmohan, Sivakumar Anusha, Vasudevan Dinakaran, Kumaravel Velayutham, Ganesan Divya, Eldho Paul, Alexander R. Lyon, Kamaraj Raju, Ganesan Velmurugan, Subbiah Ramasamy, Krishnan Swaminathan, Balakrishnan Rekha, Maruthan Karthik, Narayanan Kalyanaraman, Mani Dhivakar, Balakrishnan Jeyakumar
Přispěvatelé: Madurai Kamaraj University, Georgia State University, University System of Georgia (USG), Kovai Medical Centre and Hospital, Nutrition, diabète et cerveau (NUDICE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Madras Christian College, National Institute of Child Health and Human Development [Bethesda], National Institutes of Health, Alpha Hospital and Research Centre [Madurai], Royal Brompton Hospital, Imperial College London, Di Carlo, Marie-Ange
Rok vydání: 2016
Předmět:
0301 basic medicine
Blood Glucose
Insecticides
010501 environmental sciences
Gut flora
medicine.disease_cause
01 natural sciences
Esterase
chemistry.chemical_compound
Feces
Mice
Metatranscriptomics
2. Zero hunger
Glucose tolerance test
biology
medicine.diagnostic_test
Organophosphate
Diabetes
Organophosphates
3. Good health
Biochemistry
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
medicine.medical_specialty
Gut microbiota
Acetic acid
Fecal transplantation
03 medical and health sciences
Diabetes mellitus
Internal medicine
Glucose Intolerance
medicine
Diabetes Mellitus
Animals
Humans
Metabolomics
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
0105 earth and related environmental sciences
Research
Gluconeogenesis
Glucose Tolerance Test
biology.organism_classification
medicine.disease
Gastrointestinal Microbiome
Transplantation
Disease Models
Animal
Oxidative Stress
030104 developmental biology
Endocrinology
chemistry
Hyperglycemia
Oxidative stress
Biomarkers
Zdroj: Genome Biology
Genome Biology, BioMed Central, 2017, 18 (1), ⟨10.1186/s13059-016-1134-6⟩
ISSN: 1474-760X
1465-6906
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1134-6) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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