Inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn's disease, is a chronic, relapsing, inflammatory disorder of the gastrointestinal tract. IBD manifests in abdominal pain, vomiting, diarrhea, and rectal bleeding, and significantly impacts patients’ quality of life [1, 2]. The pathogenesis of IBD is complex, but the rapid increase in the incidence of IBD over the past decades in Asian countries suggests that environmental factors play an important role in disease development [2]. Dietary factors appear to play a role in triggering disease flares or modulating disease phenotypes; however, the underlying mechanisms remain unclear [3], [4], [5], [6].

The Western diet, characterized by high fat and sugar contents, has been linked to the increased incidence of chronic diseases, including obesity [7], type 2 diabetes [8], cardiovascular disease [9], and cancer [10]. Recent epidemiological and experimental studies have demonstrated that a high-fat diet (HFD) can trigger IBD [5, [11], [12], [13], [14]]; however, the role of sugars in IBD pathogenesis remains controversial. Although sugars are ubiquitous in the human diet and are consumed in various forms, the consumption of sugar-sweetened beverages (SSBs), such as soft drinks, fruit drinks, iced teas, energy drinks, and vitamin waters, may contribute to excessive sugar intake [15]. The consumption of SSBs has increased over the last decades worldwide [16], particularly in developing countries, owing to widespread urbanization and SSB market expansion [17, 18]. Studies have shown that patients with IBD tend to consume more SSBs than healthy individuals [19, 20]. In addition, dietary surveys have indicated that some patients with IBD believe that SSBs trigger disease flare-ups and exacerbate the severity of symptoms [21, 22]. Recent large-scale epidemiological studies have indicated that SSB consumption increases the risk of early-onset colorectal cancer [23, 24]. Despite accumulating data indicating the detrimental effect of SSBs on gut health, the precise mechanisms of action underlying the inflammation are poorly understood.

Gut microbial diversity and composition undergo alterations in response to different dietary habits [25]. Individuals living in urban areas are at an increased risk of developing immune-mediated disorders, such as IBD, which are probably associated with an altered gut microbiome attributed to dietary differences [26]. These disorders are often attributed to incompatibilities between the diets available in modern environments and those that existed during human evolution [27]. Given the fundamental roles of the intestinal microbiota in immune regulation and IBD pathogenesis, it is reasonable to speculate that dietary changes can induce alterations in the gut microbiome and immunity and thus play a central role in the increasing prevalence of IBD. However, few studies have specifically examined diet-induced changes in the gut microbiome and IBD in humans or in animal models.

Therefore, in the present study, we hypothesized that dietary challenges, especially SSBs, alter the gut immune system by inducing changes in the gut microbiota, eventually triggering IBD. To test this hypothesis, we compared the gut microbiome, immune-cell composition, and gene expression in intestinal tissues of mice administered a sucrose solution and either a normal-fat diet (ND) or an HFD. The significance of the gut microbiota in mediating the host immune response was evaluated in fecal microbiota transplantation experiments using a mouse model of dextran sulfate sodium (DSS)-induced IBD. Finally, to investigate the clinical relevance of our findings, we evaluated potential correlations between diets (high in SSBs and/or an HFD) and IBD-related inflammation in a cross-sectional human study.