Fructose catabolism and its metabolic effects: Exploring host-microbiota interactions and the impact of ethnicity

Important health disparities are observed in the prevalence of obesity and associated non-communicable diseases (NCDs), including type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) among ethnic groups. Yet, the underlying factors accounting for these disparities remain poorly understood. Fructose has been widely proposed as a potential mediator of these NCDs, given that hepatic fructose catabolism can result in deleterious metabolic effects, including insulin resistance and hepatic steatosis. Moreover, the fermentation of fructose by the gut microbiota can produce metabolites such as ethanol and acetate, both which serve as potential substrates for de novo lipogenesis (DNL) and could therefore contribute to the development of these metabolic conditions. Significant inter-ethnic differences in gut microbiota composition have been observed. Moreover, fructose consumption varies across ethnic groups, and fructose intake has been demonstrated to significantly alter gut microbiota composition, which can influence its fermenting properties and metabolic effects. Therefore, ethnic differences in gut microbiota composition, which may be influenced by variations in fructose consumption, could contribute to the observed health disparities. This review provides an overview of the complex interactions between host and microbial fructose catabolism, the role of ethnicity in shaping these metabolic processes and their impact on host health. Understanding these interactions could provide insights into the mechanisms driving ethnic health disparities to improve personalized nutrition strategies. KEY POINTS: Dietary fructose consumption has increased substantially over recent decades, which has been associated with the rising prevalence of obesity and non-communicable diseases (NCDs) such as type 2 diabetes and metabolic dysfunction-associated steatotic liver disease. Pronounced disparities among different ethnic groups in NCD prevalence and dietary fructose consumption underscore the need to elucidate the underlying mechanisms of fructose catabolism and its health effects. Together with the well-known toxic effects of hepatic fructose catabolism, emerging evidence highlights a role for the small intestinal microbiota in fermenting sugars like fructose into various bacterial products with potential deleterious metabolic effects. There are significant ethnic differences in gut microbiota composition that, combined with varying fructose consumption, could mediate the observed health disparities. To comprehensively understand the role of the gut microbiota in mediating fructose-induced adverse metabolic effects, future research should focus on the small intestinal microbiota. Future research on fructose - microbiota - host interactions should account for ethnic differences in dietary habits and microbial composition to elucidate the potential role of the gut microbiota in driving the mentioned health disparities.