(PTFS21-06-24) Ketogenic Diets With Disparate Fat Sources Protect From Experimental Colitis With Pronounced Benefit From Linoleic Acid Over Saturated Fatty Acids

Objectives: Ketogenic diets (KDs) have been studied in preclinical models of intestinal diseases, but there is little knowledge on how the fat source of these diets influences intestinal health. The objective of this study was to investigate the effects of KDs with different fat sources on experimental colitis.

Methods: Nine-week-old male C57BL/6J mice (n = 36) were fed with a low-fat control diet (CD) or KD rich in either saturated fatty acids (57 E%) (SFA-KD) or polyunsaturated linoleic acid (45 E%) (LA-KD) for 4 weeks after which colitis was induced with 2.5 % (w/v) dextran sodium sulfate (DSS). Macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate (FITC)-dextran, colonic expression of tight junction (TJ) proteins analyzed with Western Blot and RT-qPCR, and inflammatory markers analyzed with RT-qPCR were compared between groups.


Results: While the effect was more pronounced in LA-KD, both KDs mitigated DSS-induced colitis based on less weight loss (18.9 ± 8.8 % in CD, 7.4 ± 6.5 % in SFA-KD, and 4.7 ± 6.8 % in LA-KD) and preservation of colon length (6.3 ± 0.2 cm in healthy controls, 5.0 ± 0.4 cm in CD, 5.4 ± 0.6 cm in SFA-KD, and 6.1 ± 0.6 cm in LA-KD). Colonic crypt loss, epithelial erosion, and damage to the intestinal layers was reduced in KD groups (tissue damage score of 2.1/3 in CD, 1.1/3 in SFA-KD, and 0.4/3 in LA-KD). Lamina propria immune cell infiltration was less pronounced with KDs (infiltration score of 2.2/3 in CD, 1.1/3 in SFA-KD, and 0.1/3 in LA-KD). In CD, the mRNA expression of inflammatory markers was upregulated: Il1b increased by 25-fold, Il6 by 35-fold, Lcn2 by 40-fold, and Tnf by 6-fold. With KDs, Il1b, Il6, and Lcn2 increased only by 5-fold in SFA-KD and 2-fold in LA-KD. Tnf transcription increased 2-fold in SFA-KD, and remained on a healthy level in LA-KD. While there were no significant between-group differences in permeability to FITC-dextran in DSS-treated groups, LA-KD preserved TJ protein expression on a level similar to healthy controls.

Conclusions: Ketogenic diets may have preventive potential against intestinal inflammation, with the level of effect being dependent on the dietary fat source.

Funding Sources: This study was funded by Finnish Cultural Foundation, The Finnish Concordia Fund, Mary and Georg C. Ehrnrooth’s foundation, and Finska Läkaresällskapet.