# Effects of Fipronil Exposure on Glucose Metabolism Disorder via the Gut Microbiota and Inflammation

## TL;DR

Fipronil, an insecticide, disrupts glucose metabolism in mice by altering gut bacteria and causing inflammation, which could increase diabetes risk.

## Contribution

This study reveals a novel link between fipronil exposure, gut microbiota dysbiosis, and glucose metabolism disruption.

## Key findings

- Fipronil impaired glucose tolerance in normal-diet mice and worsened insulin resistance in high-fat diet mice.
- Fipronil exposure reduced Akkermansia muciniphila abundance and increased systemic inflammation.
- Fipronil decreased serum FGF15 and elevated bile acids, suggesting disruption of the FGF15-bile acid axis.

## Abstract

Fipronil (FPN), a widely used insecticide, poses health risks through environmental contamination. Although its toxicity is increasingly recognized, the impact of fipronil on glucose metabolism remains poorly understood. In this study, mice on a normal diet (ND) or high-fat diet (HFD) received a daily oral administration of fipronil (0, 0.25, 1, or 4 mg/kg) for 35 days. Blood glucose and insulin were measured, and glucose/insulin/pyruvate tolerance tests were performed. We found that fipronil compromised glucose tolerance in mice fed an ND. Gut microbiota composition was assessed by 16S rRNA sequencing and the expression of inflammatory factors was detected in the tissues. Serum fibroblast growth factor 15 (FGF15) and bile acid were determined. In HFD-fed mice, fipronil exacerbated glucose metabolic disorders and enhanced insulin resistance. These metabolic disturbances were associated with gut microbiota dysbiosis, particularly a marked reduction in Akkermansia muciniphila (A. muciniphila) abundance, and increased systemic inflammation. Fipronil exposure also decreased serum FGF15 and elevated serum bile acids. Our results suggest that fipronil disrupts glucose metabolism in association with gut microbiota alterations, impairment of the FGF15-bile acid axis, and induction of inflammation, highlighting its potential relevance to diabetes risk. Further studies are warranted to validate our findings.