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The Ability of Glyphosate to Impair Metabolic Homeostasis Via the Gut Microbiome and Metabolites

草甘膦通过肠道微生物组和代谢物损害代谢稳态的能力

基本信息

批准号：
10420400
负责人：
Frank Anthony Duca
金额：
$ 34.36万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-21 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10420400
关键词：
Adult Affect Agriculture Antibiotics Bacteria Bile Acids Chemicals Chlorinated Hydrocarbons Chronic Complex Coupled Data Development Diabetes Mellitus Disease Dose Economic Burden Elderly Environment Environmental Exposure Environmental Impact Enzymes Exhibits Exposure to Female Genetic Germ-Free Glucose Goals Health Herbicides High Fat Diet Homeostasis Human Impairment Incidence Industry Insecticides Intestines Knockout Mice Lead Life Link Malignant Neoplasms Mammalian Cell Mammals Metabolic Metabolic Diseases Metabolic dysfunction Metabolic syndrome Metabolism Mus Non-Insulin-Dependent Diabetes Mellitus Obesity Pathway interactions Pesticides Physiological Plants Play Prevalence Rattus Receptor Activation Receptor Signaling Regulation Research Role Roundup Safety Signal Pathway Signal Transduction Small Intestines Testing Time United States Weaning Weight Gain Work antagonist bacterial metabolism bile acid metabolism blood glucose regulation environmental chemical environmental chemical exposure glyphosate gut microbiome gut microbiota impaired glucose tolerance insight male metabolic abnormality assessment microbial microbiota obesity development obesity risk obesity treatment receptor shikimate social targeted treatment

项目摘要

PROJECT SUMMARY The prevalence of obesity and diabetes continue to rise unabated in the United States, creating a grave social and economic burden. Although development of these diseases is multi-faceted and complex, there is accumulating evidence for the impact of environmental chemical exposures on metabolic homeostasis. Currently, glyphosate is the most commonly used herbicide in the United States, however, to date, no studies have ever assessed whether glyphosate exposure impacts the development of obesity and diabetes. Thus, the long-term goal of this project is to better understand how recent and current pesticide usage can impact long-term metabolic homeostasis. Glyphosate targets the shikimate pathway found in plants, and not mammals, leading to the assumption of its general safety. However, glyphosate can also target bacteria, and glyphosate exposure results in an altered gut microbiome profile. Despite the fact that previous pesticides are associated with metabolic disease, and that glyphosate is known to alter the gut microbiota which can impact energy and glucose homeostasis, no study has ever examined whether exposure to glyphosate can result in development of obesity and/or diabetes. One of the main roles of the gut microbiota is bile acid metabolism, and studies suggest that alterations in bile acid signaling represent a plausible link between the gut microbiota and regulation of metabolic homeostasis via changes in Farnesoid X receptor (FXR) signaling. These facts, coupled with our preliminary data, led to the hypothesis that exposure to glyphosate shifts the gut microbiome, leading to altered intestinal bile acid signaling that contributes to impairments in energy and glucose homeostasis. This hypothesis will be tested in 3 aims: 1) assess if exposure to glyphosate during different developmental timepoints promotes metabolic dysfunction in male and female mice on a chow or high-fat diet, 2) determine the role of the gut microbiome in the effects of glyphosate exposure on metabolic homeostasis, and 3) identify the impact of altered bile acid signaling via glyphosate exposure in impaired metabolic homeostasis. The proposed study will be the first ever to provide mechanistic insight of the effects of glyphosate exposure on metabolic homeostasis. This proposal will provide valuable data leading to further research examining how environmental pesticide usage can affect human health, and possibly identify microbial targets to offset the detrimental effects of environmental chemical use.

项目总结