Sugar-sweetened beverages exacerbate high-fat diet-induced inflammatory bowel disease by altering the gut microbiome.

High-fat diets (HFDs) and frequent consumption of sugar-sweetened beverages (SSBs) are potential contributors to increasing inflammatory bowel disease (IBD) incidences. While HFDs have been implicated in mild intestinal inflammation, the role of sucrose in SSBs remains unclear. Therefore, we studied the role of SSBs in IBD pathogenesis in a mouse model and humans. C57BL6/J mice were given ad libitum access to a sucrose solution or plain water for 10 weeks, with or without an HFD. Interestingly, sucrose solution consumption alone did not induce gut inflammation in mice; however, when combined with an HFD, it dramatically increased the inflammation score, submucosal edema, and CD45 cell infiltration. 16S ribosomal RNA gene-sequencing revealed that sucrose solution and HFD co-consumption significantly increased the relative abundance of IBD-related pathogenic bacteria when compared with HFD consumption. RNA sequencing and flow cytometry showed that co-consumption promoted pro-inflammatory cytokine and chemokine synthesis, dendritic-cell expansion, and IFN-γTNF-αCD4 and CD8 T-cell activation. Fecal microbiota transplantation from HFD- and sucrose water-fed mice into gut-sterilized mice increased the susceptibility to dextran sulfate sodium-induced colitis in the recipient mice. Consistent herewith, high consumption of SSBs and animal fat-rich diets markedly increased systemic inflammation-associated IBD marker expression in humans. In conclusion, SSBs exacerbate HFD-induced colitis by triggering a shift of the gut microbiome into a pathobiome. Our findings provide new insights for the development of strategies aimed at preventing IBD.