Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review

Adv Nutr. 2020 Jan 1;11(1):77-91. doi: 10.1093/advances/nmz061.


The intestinal tract is the largest barrier between a person and the environment. In this role, the intestinal tract is responsible not only for absorbing essential dietary nutrients, but also for protecting the host from a variety of ingested toxins and microbes. The intestinal barrier system is composed of a mucus layer, intestinal epithelial cells (IECs), tight junctions (TJs), immune cells, and a gut microbiota, which are all susceptible to external factors such as dietary fats. When components of this barrier system are disrupted, intestinal permeability to luminal contents increases, which is implicated in intestinal pathologies such as inflammatory bowel disease, necrotizing enterocolitis, and celiac disease. Currently, there is mounting evidence that consumption of excess dietary fats can enhance intestinal permeability differentially. For example, dietary fat modulates the expression and distribution of TJs, stimulates a shift to barrier-disrupting hydrophobic bile acids, and even induces IEC oxidative stress and apoptosis. In addition, a high-fat diet (HFD) enhances intestinal permeability directly by stimulating proinflammatory signaling cascades and indirectly via increasing barrier-disrupting cytokines [TNFα, interleukin (IL) 1B, IL6, and interferon γ (IFNγ)] and decreasing barrier-forming cytokines (IL10, IL17, and IL22). Finally, an HFD negatively modulates the intestinal mucus composition and enriches the gut microflora with barrier-disrupting species. Although further research is necessary to understand the precise role HFDs play in intestinal permeability, current data suggest a stronger link between diet and intestinal disease than was first thought to exist. Therefore, this review seeks to highlight the various ways an HFD disrupts the gut barrier system and its many implications in human health.

Keywords: bile acids; gut barrier; gut microbiota; high-fat diet; inflammation; inflammatory bowel disease; intestinal permeability; shedding-proliferation axis; superficial unstirred mucus layer; tight junction.

Publication types

  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • Cytokines / metabolism*
  • Diet, High-Fat / adverse effects*
  • Dietary Fats / adverse effects*
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / microbiology
  • Humans
  • Inflammation / etiology*
  • Inflammation / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Mucus / metabolism
  • Permeability
  • Tight Junctions / drug effects*


  • Bile Acids and Salts
  • Cytokines
  • Dietary Fats