Synergy of secoisolariciresinol diglucoside and fructooligosaccharide in enhancement of the intestinal mucus barrier by relieving ER stress and regulating the gut microbiome.

The impairment of the intestinal barrier and the high incidence of gastrointestinal diseases can be caused by poor dietary patterns, such as long-term high-fat diets. The mucous layer, 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 an effective way to enhance the intestinal mucus barrier. On the other hand, mucins are influenced by the gut microbiome. Mucin-associated bacteria can 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 investigated 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 in the colon, inhibited mRNA expression of proinflammatory cytokines, and improved the mucosal barrier. Notably, the synergistic treatment exhibited a better effect. Goblet cell differentiation was promoted, consistent with the relief of ER stress, and SDG might be superior in this process. FOS primarily regulated the gut microbiota, enriched mucus-associated bacteria, and increased the content of metabolite short-chain fatty acids (SCFAs). The simultaneous treatment displayed a synergistic effect. The results indicated that the synergistic treatment had a stronger effect on enhancing the intestinal mucus barrier from dual approaches of relieving ER stress and regulating gut microbiota. This study provides a novel viewpoint and strategy for improving intestinal health.