Low-grade endotoxemia, diet, and gut microbiota – an emphasis on the early events leading to dysfunction of the intestinal epithelial barrier

Abstract

Low-grade chronic systemic inflammation has been shown to possess the potential to cause obesity, metabolic syndrome, and insulin resistance. Numerous studies have provided insight into the mechanisms by which dietary fat can cause the absorption or permeation of lipopolysaccharides (LPS) present in the gut bacteria into systemic circulation. Additionally, studies have deciphered the vital role of the innate immune system in linking gut microflora and inflammation. High-throughput sequencing has enabled metagenomic analyses, revealing changes in the gut microbiota composition incurred by high-fat diet. Further insights into the pathophysiological understanding of the interplay between innate immunity, metabolism, and microbiota would help improve therapeutics. This article focuses on the early events leading to the dysfunction of the intestinal epithelial barrier with additional emphasis on the technical problems encountered in in vivo and in vitro experiments. Emerging research results stress the importance of the interaction of LPS with dietary fatty acids and bile acids, as factors that impact the integrity of the gut barrier. Recent findings related to Akkermansia muciniphila and the endocannabinoid system are insightful and indicative of their potential usefulness for therapeutics. Detoxification and tolerance of endotoxin are areas where future developments can be expected. Although not a non-systematic review, this article focuses on the studies that help untangle complicated interplay between microbiology, biochemistry, and immunology.