Understanding the effect of a ketogenic diet in colitis
Final Report Abstract
A ketogenic diet (KD) is a high-fat and low-carbohydrate diet, leading to a state of ketosis characterized by elevated levels of circulating ketone bodies. Growing evidence suggests that both KD and ketone bodies exhibit beneficial effects in various pathophysiological conditions. In a preliminary experiment we could show a protective effect of a prophylactic dietary treatment with a ketogenic diet as compared to a classic high-carbohydrate standard diet in the dextran sodium sulfate (DSS) mouse model of colitis. The aim of the project was to examine the role and mechanisms of a KD and/or ketone bodies as disease-modifying approach for inflammatory bowel disease. Furthermore, the metabolic safety of different compositions of a KD should be assessed in a long-term feeding study. Different mouse models of colitis were applied to assess and compare the impact of KD feeding and supplementation with ketone ester (KE), an ingestible form of ketone bodies, on intestinal inflammation. To our surprise, KD feeding did not result in an improvement of disease activity in DSS- as well as TNBS-induced colitis. As a consequence, the metabolic safety of different compositions of a KD was not further investigated. However, as the health effects of KD in the context of other inflammatory diseases may be associated with an altered gut microbiome, we studied the effect of KD feeding on the colonic microbiome. Our results showed distinct changes in the total number of gut bacteria following the KD administration in addition to a change in the composition of the microbiome. These observed alterations could indicate possible anti-inflammatory and anti-diabetic effects of KD. However, since overall changes of the microbiota seem low, KD effects might be linked to differential abundance of only a few key genera in mice. In contrast to KD administration, KE supplementation alleviated experimental colitis in both mouse models investigated. The colitis-protective effect seemed to be more pronounced with preventive intake of KE than with therapeutic supplementation. Furthermore, the KE-induced alleviation of colitis was accompanied by elevated mucin2 expression, indicating a mucus barrier protective effect. Consistently, KE supplementation was also associated with an improvement in goblet cell function and differentiation. Our results suggest that KE represent an effective anti-inflammatory dietary supplement in the context of acute colitis and may offer a promising approach as an adjunctive nutritional therapy for patients with inflammatory bowel disease.
Publications
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Knock-In Mice Expressing a 15-Lipoxygenating Alox5 Mutant Respond Differently to Experimental Inflammation Than Reported Alox5−/− Mice. Metabolites, 11(10), 698.
Marbach-Breitrück, Eugenia; Rohwer, Nadine; Infante-Duarte, Carmen; Romero-Suarez, Silvina; Labuz, Dominika; Machelska, Halina; Kutzner, Laura; Schebb, Nils Helge; Rothe, Michael; Reddanna, Pallu; Weylandt, Karsten H.; Wieler, Lothar H.; Heydeck, Dagmar & Kuhn, Hartmut
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Microbiota profiling in aging-associated inflammation and liver degeneration. International Journal of Medical Microbiology, 311(4), 151500.
Baumann, Anja; Hernández-Arriaga, Angélica; Brandt, Annette; Sánchez, Victor; Nier, Anika; Jung, Finn; Kehm, Richard; Höhn, Annika; Grune, Tilman; Frahm, Christiane; Witte, Otto Wilhelm; Camarinha-Silva, Amélia & Bergheim, Ina
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Omega‐3 fatty acids protect from colitis via an Alox15‐derived eicosanoid. The FASEB Journal, 35(4).
Rohwer, Nadine; Chiu, Cheng‐Ying; Huang, Dan; Smyl, Christopher; Rothe, Michael; Rund, Katharina M.; Helge, Schebb Nils; Kühn, Hartmut & Weylandt, Karsten‐Henrich
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Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators—What is the Evidence so far?. Frontiers in Pharmacology, 13.
Schebb, Nils Helge; Kühn, Hartmut; Kahnt, Astrid S.; Rund, Katharina M.; O.’Donnell, Valerie B.; Flamand, Nicolas; Peters-Golden, Marc; Jakobsson, Per-Johan; Weylandt, Karsten H.; Rohwer, Nadine; Murphy, Robert C.; Geisslinger, Gerd; FitzGerald, Garret A.; Hanson, Julien; Dahlgren, Claes; Alnouri, Mohamad Wessam; Offermanns, Stefan & Steinhilber, Dieter
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Ketogenic Diet Has Moderate Effects on the Fecal Microbiota of Wild-Type Mice. Nutrients, 15(21), 4629.
Rohwer, Nadine; El Hage, Racha; Smyl, Christopher; Ocvirk, Soeren; Goris, Tobias; Grune, Tilman; Swidsinski, Alexander & Weylandt, Karsten-H.
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Prevention of colitis-induced liver oxidative stress and inflammation in a transgenic mouse model with increased omega-3 polyunsaturated fatty acids. Redox Biology, 64, 102803.
Rohwer, Nadine; Jelleschitz, Julia; Höhn, Annika; Weber, Daniela; Kühl, Anja A.; Wang, Chaoxuan; Ohno, Rei-Ichi; Kampschulte, Nadja; Pietzner, Anne; Schebb, Nils Helge; Weylandt, Karsten-H. & Grune, Tilman
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Transgenic mice overexpressing human ALOX15 under the control of the aP2 promoter are partly protected in the complete Freund’s adjuvant-induced paw inflammation model. Inflammation Research, 72(8), 1649-1664.
Heydeck, Dagmar; Kakularam, Kumar R.; Labuz, Dominika; Machelska, Halina; Rohwer, Nadine; Weylandt, Karsten & Kuhn, Hartmut
