Dietary phosphate exacerbates intestinal inflammation in experimental colitis

Area of Science:

• Gastroenterology
• Nutrition Science
• Immunology

Background:

• Western diets and food additives contribute to excessive inorganic phosphate intake globally.
• The specific impact of dietary phosphate on inflammatory bowel disease (IBD) development remains largely unknown.
• Understanding phosphate's role is crucial for managing IBD.

Purpose of the Study:

• To investigate the effects of dietary phosphate on experimental colitis.
• To determine if high phosphate intake exacerbates intestinal inflammation.
• To explore the underlying mechanisms of phosphate-induced inflammation.

Main Methods:

• Rats were fed varying phosphate diets (0.5%, 1.0%, 1.5%) with or without dextran sulfate sodium to induce colitis.
• In vitro studies examined phosphate's effects on RAW264.7 macrophages, assessing cytokine induction and reactive oxygen species (ROS) production.
• Key markers of inflammation, including clinical scores, colon length, histology, myeloperoxidase activity, and cytokine mRNA expression, were analyzed.

Main Results:

• Dietary phosphate significantly exacerbated intestinal inflammation in a dose-dependent manner.
• High phosphate diets increased myeloperoxidase activity and proinflammatory cytokine mRNA via nuclear factor-κB (NF-κB) activation.
• In vitro, high phosphate loading directly enhanced ROS production and proinflammatory cytokine gene expression in macrophages.

Conclusions:

• High dietary phosphate intake worsens experimental colitis.
• Phosphate exacerbates intestinal inflammation through mechanisms involving oxidative stress and NF-κB activation.
• These findings suggest that dietary phosphate modulation could be a therapeutic strategy for IBD.