(P19-010-25) Effect of a High-Fat Diet Combined With Arsenic Exposure on Gut Microbial Composition and Intestinal Permeability

Objectives: This study aims to evaluate the effects of low-dose arsenic exposure through drinking water, a high-fat diet, or their combination on intestinal permeability and gut microbial composition in a murine model.

Methods: Mice were divided into 4 groups: Control diet, Control diet with Arsenic exposure (100 μg/L), High Fat Diet (39.1%), and High Fat Diet with Arsenic exposure. DNA was extracted from cecal contents, and intestinal microbiota characterization was performed by amplification and sequencing of the 16S rRNA gene. RNA was extracted from colon tissues using TRIzol reagent and gene expression analysis was performed by RT PCR.

Results: The analysis of the intestinal microbiota showed a decreased abundance of genera such as Akkermansia and Bacteroides in mice fed a high-fat diet but no changes in combination with arsenic. Although, the abundance of Akkermansia also decreased with arsenic exposure in a control diet. On the contrary, mice fed a high-fat diet showed a greater abundance of Lactobacillus and Bifidobacterium. In addition, mice fed with a high-fat diet showed significantly lower gene expression of tight junctions (OCLN, ZO-1, and CLDN-7). Yet, arsenic exposure alone or in combination with a high-fat revealed no significant changes in gene expression with the tested dose. Interestingly, we observed significant correlation between differentiated taxa and markers of intestinal permeability and systemic inflammation. Particularly a negative correlation between Bifidobacterium abundance with tight junction’s gene expression and TNFα levels was observed. In contrast, Bacteroides abundance showed a positive correlation with tight junction gene expression and negative with serum levels of TNFα.

Conclusions: These results suggest that low-dose arsenic exposure may ameliorate the detrimental effect of a high-fat diet on the markers of intestinal permeability and systemic inflammation which might be related to changes in the intestinal microbiota.

Funding Sources: CONAHCYT