Abstract
PURPOSE: A ketogenic diet (KD), high in fat and low in carbohydrates, induces ketosis characterized by elevated circulating ketone bodies. While both KD and ketone bodies have demonstrated therapeutic potential in various pathophysiological conditions, their effect on inflammatory bowel diseases remains controversial. This study aimed to investigate the impact of a KD and ketone ester (KE), an ingestible form of ketone bodies, on intestinal inflammation. METHODS: Acute dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced murine colitis models were used to evaluate and compare the effects of KD feeding and KE supplementation on intestinal inflammation, the mucus barrier and gut microbiota composition. RESULTS: KD feeding did not significantly affect colitis activity, whereas KE supplementation alleviated colitis in both models investigated. KE-induced mitigation of colitis was associated with increased mucin2 expression, indicating enhanced colonic mucus barrier integrity. KE supplementation also improved goblet cell function and differentiation, as evidenced by increased goblet cell numbers and the upregulation of goblet cell differentiation markers. Furthermore, 16S rRNA sequencing analysis revealed that KE supplementation resulted in higher abundances of mucus-degrading Akkermansia, a genus believed to play a key role in maintaining intestinal homeostasis. CONCLUSION: The present study suggests that KE represent an effective anti-inflammatory dietary supplement in the context of acute colitis, potentially by modulating mucin2 expression, goblet cell differentiation, and the abundance of Akkermansia. Although promising, these findings remain preliminary, and further investigations are needed to explore the therapeutic potential of KE as a dietary supplement in patients with inflammatory bowel disease.