Exploring the impact of myoglobin from red meat on intestinal function: Insights from mouse and cell models

Abstract

Abstract Excessive intake of red meat may cause damage to colorectal tissue but not cause significant damage to the small intestine. However, the underlying mechanism is not clear. In this study, the effect of myoglobin extracted from red meat was explored on the intestinal barrier function of the mice, and its potential mechanism was elucidated through cell culture experiments. Exclusively high‐dose myoglobin (3.39%, equivalent to 450 g red meat per day for human) resulted in marked intestinal permeability with increased levels of serum endotoxin, diamine oxidase, and d‐lactate but reduced the mRNA levels of tight junction proteins and mucin 2 in the duodenal and colonic tissues. The diet also increased free iron and heme levels in the duodenal and colonic tissues, leading to higher level of oxidative stress and inflammatory response. Metabolomic analysis of colonic contents showed that exclusively high‐dose myoglobin altered the relative content of indole and its derivatives, phenolic compounds, and 5‐hydroxy‐l‐tryptophan by regulating tryptophan metabolism and kynurenine cycle and destroying intestinal homeostasis. The very high myoglobin hydrolysate induced oxidative stress and apoptosis more seriously in HT29 cells than in INT407 cells, which could be the main reason for more severe colon injury. Nevertheless, normal low‐dose intake (0.38% myoglobin, equivalent to 50 g per day for human) did not show the above‐mentioned harmful effects. The findings provided a risk assessment for the dosage of red meat intake and new insights into the relationship between red meat intake and intestinal health.

Keywords

• heme
• intestinal barrier
• metabolites
• myoglobin
• oxidative stress