Organophosphorus pesticide chlorpyrifos intake promotes obesity and insulin resistance through impacting gut and gut microbiota Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Read MoreKaren Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Lipopolysaccharide (LPS)
Lipopolysaccharide (LPS)
Lipopolysaccharide (LPS), a potent endotoxin present in the outer membrane of Gram-negative bacteria that causes chronic immune responses associated with inflammation.
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Karen Pendergrass
Read More
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was studied?
This study investigated how chronic exposure to the organophosphorus pesticide chlorpyrifos contributes to obesity and insulin resistance (IR) through its impact on gut microbiota and gut barrier integrity. Using C57Bl/6 and CD-1 (ICR) mice fed either normal-fat or high-fat diets, researchers evaluated the effects of chlorpyrifos on gut permeability, microbiota composition, inflammatory responses, and metabolic outcomes such as insulin sensitivity and glucose homeostasis.
Who was studied?
The study utilized male C57Bl/6 and CD-1 (ICR) mice, chosen to represent genetic and dietary variability. Mice were divided into groups based on diet (normal-fat or high-fat) and exposure to chlorpyrifos. Antibiotic treatment and microbiota transplantation were performed to further explore the role of chlorpyrifos-induced microbiota changes in metabolic dysregulation.
What were the most important findings?
Chronic chlorpyrifos exposure disrupted the gut barrier by reducing the expression of tight junction proteins (e.g., occludin, ZO-1), leading to increased intestinal permeability. This facilitated the entry of lipopolysaccharides (LPS) into circulation, promoting low-grade inflammation. Chlorpyrifos exposure altered the gut microbiota composition, with increased Proteobacteria (a source of LPS) and decreased Bacteroidetes—microbial changes commonly associated with obesity. Antibiotic treatment reversed chlorpyrifos-induced obesity and insulin resistance, confirming that microbiota changes played a key role in these outcomes. Mice transplanted with chlorpyrifos-altered microbiota exhibited increased fat accumulation, impaired glucose tolerance, and insulin resistance, highlighting the causal role of microbiota alterations.
What are the greatest implications of this study?
This study underscores the potential role of environmental pollutants like chlorpyrifos in driving the global obesity epidemic by altering gut microbiota and promoting systemic inflammation. These findings suggest that pesticide exposure should be critically evaluated in public health policies and safety assessments. Furthermore, the study provides insights into the gut microbiota as a therapeutic target for metabolic disorders induced by environmental factors.