Long-term consumption of moderate amounts of sucrose-sweetened drinks disrupts intestinal barrier function by impairing goblet cell differentiation.

Abstract

While the prolonged consumption of sucrose-containing beverages is known to impact many organs, their specific effects on the small intestine remain elusive. This study aimed to evaluate how regular intake of sucrose, in amounts typically consumed, affects goblet cells, which play a critical role in regulating the mucosal barrier and innate immune defenses in the small intestine. Ten-week-old male ddY mice, a model of diet-induced obesity, were given a regular diet with either plain water or 7% sucrose water. Caloric intake was monitored weekly through food and drink measurements. After 8 weeks, glucose and insulin responses were evaluated following an oral gavage of glucose or sucrose. At 14 weeks, plasma, whole small intestine, and liver samples were collected. Despite achieving an isocaloric state, mice drinking sucrose water showed approximately a 1.5-fold increase in body weight and impaired glucose tolerance. In the small intestine, genes involved in sucrose digestion and absorption (Sis, Sglt1, Glut2, and Glut5) were upregulated, while genes essential for maintaining the intestinal barrier and function (Epcam, Fabp2, Cldn1, Ocln, and Tjp1) were downregulated. Serum levels and mRNA expression of the inflammatory cytokine, interleukin-18 were elevated. Genes responsible for goblet cell differentiation and function (Hes1, Gfi1, Spdef, and Klf4) were downregulated, leading to an increase in immature goblet cells and a decrease in mucin-producing markers (Muc2, Muc4, and Muc13) in the jejunum. The findings underscore that besides obesity, long-term intake of sucrose-containing drinks provokes localized inflammation and disrupts small intestinal barrier function by impairing goblet cell differentiation and activity.