While emerging evidence suggests pesticides can be toxic to the mix of microorganisms in the digestive system, a new study is the first to map changes to specific gut bacteria based on interactions between human microbes and insect-killing chemicals observed in the lab and an animal model.
The analysis showed that over a dozen pesticides influence human gut bacteria growth patterns, affect how gut microorganisms process nutrients and camp out inside some bacteria. Researchers say the resulting "atlas" of molecular mechanisms, which they have made publicly available, is a resource that can be leveraged for targeted studies on relevant diseases and potential therapeutic strategies.
Experiments in mice showed that one gut bacteria species provides some protection against pesticide toxicity, hinting at the possibility for a probiotic approach to preventing some of their damaging health effects - in this case, inflammation.
"We've provided further understanding of how pesticides or environmental pollutants impact human health by modulating an important collection of microorganisms," said senior author Jiangjiang Zhu, associate professor of human sciences at The Ohio State University.
"We also identified certain microbes that can degrade, remove or clear some of these pesticides from biological systems, which may be potential therapeutics in the future to help people clear toxicity from the gut that have been introduced by food and water intake, providing better solutions for human health."
The research was published recently in Nature Communications.
The findings are based on investigating the interactions in the lab between 18 pesticide compounds selected for their widespread agricultural use around the world and 17 species from four major bacterial domains in the human gut that are associated with either health maintenance or disease states. Among the pesticides included were DDT (banned in the United States but used indoors in some countries to control malaria-carrying mosquitoes), atrazine, permethrin and chlorpyrifos. Even with limitations on their use, residues from some legacy pesticides still circulate in soil and water, Zhu said.
"We grew bacteria in culture and exposed them to relevant concentrations of pesticides to see how microbes responded to those pesticide exposures," said first author Li Chen, a senior research associate in Zhu's lab, who managed over 10,000 samples that were analyzed in the study.
Based on the findings, the team developed a bacteria-pesticide interaction network detailing which pesticides either promoted or inhibited bacterial growth and the bacteria that absorbed pesticide chemicals - an indication of one way exposure to pesticides can be prolonged in the body.
"Most previous environmental health studies reported that pesticide contamination affects the overall composition of gut bacteria," Chen said. "We showed those pesticides really can affect specific gut bacteria and detailed how these changes will affect the general composition."
The analysis identified specific metabolic changes in 306 pesticide-gut microbe pairs, leading to examination of how those altered growth patterns and accumulation of chemicals affected metabolites - the molecular products of biochemical reactions that break down nutrients to produce energy and perform other essential functions. Metabolites have numerous roles, from altering the metabolic process itself to sending signals related to multiple cell functions and immune system activation.
In addition, the study team performed a separate analysis zeroing in on another important class of molecules that can be produced by gut microbes - the fatty, oily and waxy compounds called lipids that are essential to many body functions.
Researchers also studied the effects of pesticide exposure in healthy mice first given antibiotics to clear their digestive systems of microbes. The team introduced Bacteroides ovatus, a common strain of human gut bacteria, to one group of mice and compared them to controls after four weeks of exposure to pesticides.
Results verified what was seen in the lab, showing that pesticides generated inflammation in multiple organs in the mice and that the presence of the introduced bacteria after chemical exposure set off a range of changes in metabolic activity and lipid production. Specifically, an increase in some classes of lipids inhibited the signaling pathway of a protein linked to oxidative stress.
"We identified microbes that may modulate the toxic effect of pesticides to the host by somehow buffering the inflammation process," said Zhu, also an investigator in The Ohio State University Comprehensive Cancer Center Molecular Carcinogenesis and Chemoprevention Research Program.
"We know inflammation is generally bad for the body. If something toxic is going to induce it, and there are other molecules that can counteract that agent, you may have a solution to intervene or prevent larger-scale damage."
In the next phrase of this work, Zhu's lab plans to further explain where metabolic changes to gut microbes fit into various health and disease conditions after pesticide exposure. He expects other scientists will do the same.
"We are mapping out this central interaction between pesticides and gut microbes. And then other labs can leverage what we have discovered - for example, after exposure to a pesticide, gut microbe reactions may lead to downstream consequences that contribute to disease research and eventually help with predicting targets or identifying an intervention strategy," he said.
This research was supported by the National Institute of General Medical Sciences. Zhu is also supported by the Provost's Scarlet and Gray Associate Professor Program at Ohio State.
Additional co-authors include Chao Guo, Huan Zhang, Shiqi Zhang, Andrew Gold, Ming Hu and Dayong Wu, all of Ohio State; Hong Yan and Caroline Johnson of Yale University; Shanshan Di and Xinquan Wang of Zhejiang Academy in Hangzhou, China; and Yu Wang of Johns Hopkins University.
