Red snapper protein prevents chronic unpredictable mild stress-induced ileal barrier damage by reversing microbiota-derived butyric acid overload

Abstract

Chronic unpredictable mild stress (CUMS) can cause numerous physical and mental health problems, with gut barrier damage being a critical causative factor. Although dietary red snapper (scientific name: Lutjanus erythropterus) protein (DRSP) has the potential to prevent and repair gut barrier damage, its exact role and mechanism of action are unknown. This study utilized a 14, 28, and 42-day CUMS model to examine the protective and restorative effects of DRSP on ileal mucosal barrier damage (IMBD) in male C57BL/6 mice. At the late CUMS stage (42 days), numerous ileal lumen bacteria, including Muribaculaceae, Butyricoccus, Ruminococcus, Roseburia, and Eubacterium, utilized specific amino acids (AAs) (threonine, aspartic, glycine, glutamic, alanine) to produce butyric acid (BA), leading to a deficiency of these AAs. This resulted in a decrease in the abundance of bacterial genera that depend on these specific AAs for growth (Barnesiella, Lactobacillus, Prevotella, Turicibacter, and Blautia), which in turn further promoted the proliferation of BA-producing bacteria such as Muribaculaceae, leading to an excessive accumulation of BA in the ileal lumen and inducing IMBD. The DRSP-specific AA combination can supplement the CUMS-induced AA deficiency, regulate under the influence of CUMS-affected ileal microbiota structure and its AA and short-chain fatty acid (SCFA) metabolic function changes, thereby reversing the abnormal enrichment of BA and ultimately improving CUMS-induced IMBD, which was significantly superior than with fish oil. The findings were validated through both in vitro ileal microbiota cultures and in vivo studies. This not only highlights the potential nutritional function of dietary protein but also emphasizes the importance of an appropriate AA ratio in alleviating CUMS-induced IMBD and related physical and mental health problems. In summary, this study reveals that dietary protein enriched with specific AA combinations can prevent and ameliorate CUMS-induced IMBD by modulating intestinal BA levels, providing innovative mechanistic insights for dietary intervention strategies.