Effect of Protein Fermentation Products on Gut Health Assessed in an In Vitro Model of Human Colon (TIM-2)

Mol Nutr Food Res. 2023 Feb 20;e2200574. doi: 10.1002/mnfr.202200574. Online ahead of print.


Scope: Western type of diets are characterized by high animal protein intake and are associated with various chronic inflammatory diseases. With a higher protein consumption, excess undigested protein will reach the colon and be subsequently metabolized by gut microbiota. Depending on the type of protein, fermentation in the colon generates different metabolites with varying biological effects. This study aims to compare the impact of protein fermentation products from different sources on gut health.

Methods and results: Three high protein diets (vital wheat gluten [VWG], lentil, or casein) are submitted to the in vitro model of colon. Fermentation of excess lentil protein for 72 h results in highest production of short-chain fatty acids and lowest production of branched-chain fatty acids. Exposure of Caco-2 monolayers or Caco-2 monolayers co-cultured with THP-1 macrophages to luminal extracts of fermented lentil protein results in less cytotoxicity of Caco-2 monolayers and less damage to barrier integrity, when compared to VWG and casein. Lowest induction of interleukin-6 is observed in THP-1 macrophages after treatment with lentil luminal extracts, which is identified to be regulated by aryl hydrocarbon receptor signaling.

Conclusion: The findings indicate that protein sources affect the health effects of high protein diet in the gut.

Keywords: TIM-2; aryl hydrocarbon receptor; gut microbiota; high protein diet.