March 22nd, 2022 

The deep dive into fructose metabolism continues. Now we are going to look at its effect on the microbiome induced endotoxemia, intestinal permeability and inflammation which can lead to metabolic syndrome.

From science heavy article: "Fructose drinking significantly elevated plasma

bacterial endotoxin levels, likely resulting from decreased levels of intestinal tight junction (TJ) proteins (zonula occludens 1, occludin, claudin-1, and claudin-4), adherent junction (AJ) proteins (β-catenin and E-cadherin), and desmosome plakoglobin, along with α-tubulin, in wild-type rodents, but not in fructose-exposed Cyp2e1-null mice. Consistently, decreased intestinal TJ/AJ proteins and increased hepatic inflammation with fibrosis were observed in autopsied obese people compared to lean individuals. Furthermore, histological and biochemical analyses showed markedly elevated hepatic fibrosis marker proteins in fructose-exposed rats compared to controls. Immunoprecipitation followed by immunoblot analyses revealed that intestinal TJ proteins were nitrated and ubiquitinated, leading to their decreased levels in fructose-exposed rats." (Cho et. al. 2021)

This study is critical for our understanding or more downstream risks related to unregulated fructose consumption. In the upcoming podcast with Dr. Alessio Fasano, we are going to explain in detail the reality of intestinal permeability or leaky gut as his group was one of the principle investigators to understand the science.

The fructose molecule in high volume has the ability to alter the intestinal microbiome, alter the activity of the tight junctions holding the intestinal lining impermeable and increasing systemic inflammation through multiple mechanisms including the release of lipopolysaccharide molecules from bacteria that die off in the intestine.

These effects are well known to worsen immunological inflammation leading to diabetes and heart disease as well as death from infectious diseases like influenza and SARS2-Covid.

 

Take home: avoid all beverages with high fructose corn syrup, plain fructose or the disaccharide table sugar in them.

 

Dr. M

Hepatology Cho
Yu Frontiers in Pharma