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A high-fat diet (HFD) significantly alters the expression of tight junction proteins, such as Zonula Occludens Protein-1 (ZO-1), occludin, and claudin-1. These proteins are crucial for maintaining intestinal barrier integrity, and their disruption leads to increased permeability.
HFD triggers inflammation by enhancing Human Cytokine Production production, including Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-1 beta (IL-1 beta), Interleukin-6 (IL-6), and Interferon gamma (IFN-g). These cytokines weaken the intestinal barrier and reduce the levels of barrier-forming cytokines such as Interleukin-10 (IL-10), Interleukin-17 (IL-17), and Interleukin-22 (IL-22).
HFD leads to changes in the gut microbiota, increasing harmful species while decreasing beneficial bacteria. This microbial shift exacerbates intestinal permeability.
Moreover, HFD induces oxidative stress and apoptosis in intestinal epithelial cells (IECs), further contributing to increased permeability.
Chronic consumption of an HFD has numerous detrimental effects on intestinal barrier integrity:
Tight Junction Disruption: HFD reduces the tightness of tight junctions by downregulating their protein expression or causing aberrant perijunctional-actinomyosin ring (PAR) contraction, allowing luminal components to infiltrate the lamina propria (LP).
Oxidative Stress and Apoptosis: Translocated bile and fatty acids induce oxidative stress and apoptosis in enterocytes, further compromising the lumen's tight seal.
Mucus Secretion Inhibition: Fatty acid-induced unfolded protein response (UPR) stress in goblet cells inhibits mucus secretion. Combined with an elevated hydrophobic bile acid load, this negatively impacts mucus quality and quantity, facilitating gut microbiota invasion.
Pathogenic Bacterial Growth: HFD increases the abundance of pathogenic strains, such as Desulfovibrio spp., which deconjugate TCA, producing genotoxic H2S gas.
These factors collectively promote an inflammatory response, perpetuating the cycle of intestinal barrier degeneration and predisposing the host to gastrointestinal pathologies.
see also:
Leaky Gut Syndrome