“You offer me Pesticides, I give you back Diabetes”, says Gut Bacteria

G. Velmurugan

The prevalence of diabetes has increased tremendously in recent years particularly in Asia. There is a general perception that the prevalence of diabetes, heart failure and other similar diseases are very low in villages. The reasons beyond this perception are high physical activity, healthy diet and unpolluted environment of villages. But breaking this opinion, researchers from KMCH Research Foundation revealed around 12% diabetes prevalence in villages in Erode and Madurai. This is equivalent to prevalence rate reported in urban India. In particular, they noticed a three-fold higher prevalence of diabetes among farming community on comparison with non-farming community of same rural population. On support to this data, Dr. Krishnan Swaminathan, President & Consultant Endocrinologist in KMCH Research Foundation says, “I am witnessing a large number of farmers specifically in the age group of 30-45 with diabetes in recent years”. The irony is people from farming community doesn’t have the usual risk factors of diabetes like physical inactivity, high fat diet, obesity, hypercholesterolemia and family history of diabetes.

So, we were confused on what else could be the risk factor for diabetes in rural India, he was inspired by a statement in the Silent Spring book. Silent Spring was published in 1962 and regarded as one of the most influential books that changed the world. In this book, author Rachel Carson says “As the tide of chemicals born of the industrial age arisen to engulf our environment, a drastic change has come about in the nature of the most serious health problem”. The major input from industrial revolution into villages is in the form of synthetic fertilizers and pesticides. So, the researchers made a survey on the use of agrochemicals and identified organophosphate group of insecticides constitutes the major proportion (60%) of chemicals used in the villages of Tamil Nadu. On contrast to organochlorine pesticides (Endosulfan, DDT), which are non-biodegradable and stays in environment for several years, these organophosphates has short half-life time and biodegradable and thereby today evolved as largely used agrochemical. Actually, these organophosphates are first produced during the Hitler era in Germany as chemical weapons and later some of them became insecticides. We measured the level of these insecticides such as monocrotophos, chlorpyrifos, malathion and methyl parathion in blood of the villagers and noticed a strong association with diabetes. The major target of these organophosphates is an enzyme called acetylcholine esterase that is involved in neurotransmission in both insects and humans. But the researchers observed no changes in the level of this enzyme and thereby raising the question whether really these organophosphates are a key causative factor or not?

To answer this, the researchers planned a mice study at theoretical daily intake dose, which is equivalent to the daily exposure of these insecticides in Indians. “All the previous toxicological reports with these insecticides are at acute or large doses and ours is the first report to replicate the exposure level at day to day life,” says KMCHRF team. The animals drinking organophosphate insecticide mixed water exhibited no changes in body weight, physical activity and acetylcholine esterase level even after six months. On the other hand, the blood glucose level gradually increased and the mice became diabetic with an average fasting blood glucose of 200 mg/ dl. So, the researchers are confident that organophosphate insecticides are inducing diabetes through a new route of action and not by targeting acetylcholine esterase.

Previous studies showed that these insecticides are degraded by the bacteria in the gut. Human body is a rich source of biodiversity especially, the gut is home for trillions of bacteria and other microbes that plays a key role in digestion and metabolism. These microbes determine food allergies, action of medicines, diseases and even attitude of a person. So, the researchers thought that gut bacteria may play a role in this organophosphate-induced diabetes. Using combined next generation genomics and metabolomics technologies, they proved that the organophosphates are metabolized by the gut bacteria using specific enzymes and the secondary metabolites like acetate thus produced are converted into glucose by gluconeogenesis. Gluconeogenesis is the pathway by which glucose is produced from non-carbohydrate sources like proteins or lipids. The findings from the animal study was validated in the humans from same villages by observing increased expression of organophosphate degrading enzymes and degradation by-products in fecal samples of diabetes people. So, it is clear that when you disturb the bacteria in the gut with toxic insecticides, they reply back to you by leading to diabetes state. In simple words, if you destroy nature, the nature will destroy you.

In overall, the study suggests that the wide use of these toxic insecticides could be one of the major reasons for diabetes epidemic in the South Asia. The results were published in the Journal Genome Biology in 2017. At present, the researchers at KMCH Research Foundation are involved in understanding the variation in gut bacteria composition between diabetes people in urban and rural population and aimed at developing gut bacteria based formulation for diabetes therapy. As the usual risk factors of diabetes like physical inactivity, high fat diet and obesity are absent in rural communities, the researchers suggest reframing of the control and preventive measures for diabetes. In addition, the study strongly recommends the reconsideration of the wide use of organophosphate pesticides in the world.