High-sugar and carrageenan-containing diets synergistically impair the intestinal mucosal barrier through the gut microbiota: in vitro and in vivo studies

Increased consumption of high-sugar processed foods is accompanied by a higher daily intake of food additives like carrageenan, which is strongly correlated with the development of intestinal diseases. While previous studies indicate long-term consumption of high-sugar and carrageenan-containing foods impairs colonic barrier, the underlying mechanisms remain unclear. In this study, combined in vitro and in vivo models were employed and the mediating role of gut microbiota was elucidated. In animal studies, high-sugar and carrageenan-containing diets decreased antimicrobial substances expression (lysozyme and REG3G), increased intestinal permeability, induced inflammatory cell infiltration and disrupted gut microbiota homeostasis in the colon. Compared to kappa-carrageenan (κ-CGN), iota-carrageenan (ι-CGN) caused more severe gut microbiota disruption and greater elevation of inflammatory cytokines under a high-sucrose diet. To verify the role of gut microbiota in this process, gut microbiota from high-sugar diet-fed mice was used for the in vitro simulated colonic fermentation of carrageenan. The fermentation products disrupted tight junctions, activated STAT3 and NF-κB signaling pathways, and elevated inflammatory cytokines in colonic epithelial cells, confirming the gut microbiota's crucial mediating role in this synergistic damage. Furthermore, 16S rRNA sequencing and LC-MS analysis revealed that both κ- and ι-CGN increased pro-inflammatory and dysbiosis-associated gut microbiota and metabolites within the fermentation products derived from the gut microbiota of high-sugar diet-fed mice, which represented a potential mechanism for the microbiota-mediated synergistic damaging effects. These findings provide a theoretical basis for future public health guidelines and for the food industry to develop healthier formulations, potentially mitigating the risk of diet-related gut diseases. • The diet high in sugar and carrageenan synergistically impaired the intestinal barrier. • High-sugar and carrageenan-containing diets disrupted gut microbiota homeostasis. • ι-CGN caused greater microbiota and barrier damage than κ-CGN under a high-sugar diet. • Gut microbiota mediated the diet-induced synergistic damage to the intestinal barrier.