Abstract
BackgroundOrganophosphates 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.ResultsHere 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.ConclusionCollectively, 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.
Highlights
Organophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature
Plasma OP residues associated with human diabetes Based on the survey executed among the pesticide users including pesticide applicators, farmers, and pesticide sellers in the villages of Vadapalanji Panchayat (Additional file 1: Figure S1), we found OP constitutes nearly 50% of insecticide usage
Our survey indicates the high prevalence of diabetics (18.3%) among the people directly exposed to OP insecticides while it was threefold lesser (6.2%) among the indirectly exposed group (Fig. 1a, Additional file 1: Figure S1B; adjusted odds ratio (OR), 1.4; 95% confidence interval (CI), –0.74 to 2.47; Additional file 2: Table S3)
Summary
Organophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature. We aimed to understand the role of gut microbiota in organophosphate-induced hyperglycemia and to unravel the molecular mechanism behind this process. The history of the development of OPs is amalgamated with wars [1]. They are used as pesticides in agricultural fields, as chemical weapons in war fields, as plasticizers, oil additives, and lubricants in industries. Often less than 0.1% of pesticides sprayed are estimated to reach the target organism [4], while the remainder is deposited on plant surfaces or tissues, soil, water, and air and reaches off-target organisms including humans. The existence of OP residues in different media including air, soil, water bodies, vegetables, blood, urine, and tissues of humans and other animals were detected worldwide [5, 6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
