Synergy of Secoisolariciresinol diglucoside and fructooligosaccharide on enhancement of intestinal mucus barrier based on relieving ER stress and regulating gut microbiome

Abstract

Impairment of the intestinal barrier and high incidence of gastrointestinal diseases can be caused by poor dietary patterns such as long-term high-fat diets. The mucous layer, which is composed of Mucin-2-based glycoproteins, is important for the intestinal barrier. Mucins are secreted by the goblet cells (GC), which are highly sensitive to endoplasmic reticulum (ER) stress. Therefore, promoting mucin synthesis and secretion by relieving ER stress is one of the effective ways to enhance the intestinal mucus barrier. On the other hand, mucins are influenced by the gut microbiome. Mucin-associated bacteria could degrade mucins and then stimulate goblet cells to secrete mucin. Secoisolariciresinol diglucoside (SDG) has been reported to relieve ER stress and improve the gut barrier. As a prebiotic, fructooligosaccharide (FOS) has the potential to regulate intestinal flora. In the present study, we investigate the synergistic effect of SDG and FOS on the improvement of the intestinal mucus barrier in high-fat mice. It was found that both SDG and FOS alleviated histological damage of the colon, inhibited mRNA expression of proinflammatory cytokine, and improved the mucosa barrier. Notably, the synergistic treatment exhibited a better effect. The goblet cell differentiation was promoted, which is consistent with the relief of ER stress. SDG might be superior in this process. FOS primarily regulates gut microbiota, enriches mucus-associated bacteria, and increases the content of metabolite short-chain fatty acids (SCFAs). Similarly, the simultaneous treatment displayed a synergistic effect. The results indicated the synergistic treatment had a stronger effect on enhancing the intestinal mucus barrier from dual approaches of relieving ER stress and regulating gut microbiota. The study provided a novel viewpoint and strategy for the improvement of intestinal health.