TLR4 Deficiency Affects the Microbiome and Reduces Intestinal Dysfunctions and Inflammation in Chronic Alcohol-Fed Mice

Autores de CIPF

• Carlos Manuel Cuesta Díaz

  Autor

• Maria Pascual Mora

  Autor

• Raúl Pérez Moraga

  Autor

• Irene Rodriguez Navarro

  Autor

• 

  Francisco García García

  Autor

• Juan Ramon Ureña Peralta

  Autor

• Consuelo Guerri Sirera

  Autor

Grupos de Investigación

• Unidad de Bioinformática y Bioestadística

  

  Jefe/a de Grupo

  Francisco García García

Abstract

Chronic alcohol abuse causes an inflammatory response in the intestinal tract with damage to the integrity of the mucosa and epithelium, as well as dysbiosis in the gut microbiome. However, the role of gut bacteria in ethanol effects and how these microorganisms interact with the immune system are not well understood. The aim of the present study was to evaluate if TLR4 alters the ethanol-induced intestinal inflammatory response, and whether the response of this receptor affects the gut microbiota profile. We analyzed the 16S rRNA sequence of the fecal samples from wild-type (WT) and TLR4-knockout (TLR4-KO) mice with and without ethanol intake for 3 months. The results demonstrated that chronic ethanol consumption reduces microbiota diversity and causes dysbiosis in WT mice. Likewise, ethanol upregulates several inflammatory genes (IL-1 beta, iNOS, TNF-alpha) and miRNAs (miR-155-5p, miR-146a-5p) and alters structural and permeability genes (INTL1, CDH1, CFTR) in the colon of WT mice. Our results further demonstrated that TLR4-KO mice exhibit a different microbiota that can protect against the ethanol-induced activation of the immune system and colon integrity dysfunctions. In short, our results reveal that TLR4 is a key factor for determining the gut microbiota, which can participate in dysbiosis and the inflammatory response induced by alcohol consumption.

Keywords

• TLR4; ethanol; intestinal microbiota; 16S rRNA; inflammation