High Fat Diet Accelerates Pathogenesis of Murine Crohn’s Disease-Like Ileitis Independently of Obesity

Gruber, Lisa; Kisling, Sigrid; Lichti, Pia; Martin, François-Pierre; May, Sylvio; Klingenspor, Martin; Lichtenegger, Martina; Rychlik, Michael; Haller, Dirk

doi:10.1371/journal.pone.0071661

Cited by 106 publications

(82 citation statements)

References 34 publications

(32 reference statements)

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“…Inflammatory autoimmune arthritis jci.org Volume 125 Number 6 June 2015 matory state, with increased production of cytokines known to promote Th17 differentiation, including IL-1 and IL-6 (98). Moreover, mice placed on a high-fat diet demonstrate increased expression of IL-17, IL-23p19, and RORγt consistent with increased Th17 responses and have more rapid onset of colitis (99). Similarly, mice placed on a diet rich in trans fatty acids, which are found in processed hydrogenated vegetable oil, develop more severe intestinal inflammation in response to dextran sodium sulfate, and this is associated with an increase in both IL-17 and RORγt expression (100).…”

Section: Il-23 and Autoimmunitymentioning

confidence: 92%

Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity

Burkett¹,

Hörste²,

Kuchroo³

2015

J. Clin. Invest.

199

137

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R e v i e w S e R i e S : A u t o i m m u n i t y2 2 1 2 jci.org Volume 125 Number 6 June 2015Murine Th17 differentiation can also be induced in the absence of TGF-β1 signaling, via the combination either of IL-1β, IL-6, and IL-23 or of 42). These TGF-β1-independent Th17 cells can efficiently induce autoimmune tissue inflammation upon adoptive transfer, a trait that led to them being termed "pathogenic" Th17 cells. Additionally, they possess a gene expression profile distinct from that of "nonpathogenic" Th17 cells, which are differentiated with TGF-β1 and IL-6. These observations have led to two competing hypotheses. The first posits that IL-23 cements Th17 lineage commitment such that Th17 cells induced with TGF-β1 and IL-6 are insufficiently committed to the lineage and cannot induce autoimmune tissue inflammation. The second suggests that there are distinct subtypes of Th17 cells whose differentiation is dependent on distinct combinations of cytokines. The latter hypothesis is supported by the finding that pathogenic Th17 cells express higher levels of several Th1 lineage-associated transcripts, such as the transcription factor T-bet and IFN-γ, and have been shown to be derived from IL-17 single producers by fate mapping experiments (43,44). Similarly, an important feature of human Th17 cells, as well as those isolated from inflamed tissues in mouse models of Th17-mediated disease, is that they coproduce IL-17 with other cytokines, leading to distinct functional roles (45)(46)(47). For instance, human Th17 cells that produce both IL-10 and IL-17 preferentially respond to Staphylococcus aureus, while those that produce both IL-17 and IFN-γ recognize Candida albicans, suggesting that distinct pathogens induce distinct subtypes of Th17 cells (40). IL-17/IFN-γ coproducers have been ascribed pathogenic functions in the CNS during EAE; however, it has been difficult to reliably differentiate such cells in vitro. Repeated rounds of in vitro culture in the presence of either Th1-inducing cytokines or IL-23 can induce IL-17/IFN-γ coproducers, albeit at moderate percentages. The transcription factors T-bet, RUNX1, and RUNX3 appear to be important in the acquisition of this phenotype (48,49).Large-scale transcriptional analysis of Th17 differentiation at very high temporal resolution has begun to elucidate the molecular networks that control this process, and is a promising approach to the identification of novel regulatory molecules that control pathogenic Th17 differentiation (50, 51). In fact, Th17 development is controlled induction of this lineage. The combination of TGF-β1 and IL-6 efficiently induces IL-17-producing murine T cells in vitro and highlights the reciprocal relationship between induced Tregs, which are generated by TGF-β1 alone, and Th17 cells (19,20). A series of studies demonstrated that IL-21, a γ c -dependent cytokine, could promote the differentiation of Th17 cells (21-23). In combination with TGF-β, IL-21 induces IL-17 production from naive Th cells and promotes the expression of both RORγt, th...

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Section: Il-23 and Autoimmunitymentioning

confidence: 92%

Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity

Burkett¹,

Hörste²,

Kuchroo³

2015

J. Clin. Invest.

199

137

View full text Add to dashboard Cite

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“…High-fat diets have been found to increase the severity of colitis that develops in mice 28, 29 . The essential fatty acids have been studied extensively in animal models of IBD.…”

Section: Nutrient-dependent Regulation Of Intestinal Inflammation In mentioning

confidence: 99%

Diet in the Pathogenesis and Treatment of Inflammatory Bowel Diseases

et al. 2015

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Some of the most common symptoms of the inflammatory bowel diseases (IBD, which include ulcerative colitis and Crohn’s disease) are abdominal pain, diarrhea, and weight loss. It is therefore not surprising that clinicians and patients have wondered whether dietary patterns influence the onset or course of IBD. The question of what to eat is among the most commonly asked by patients and among the most difficult to answer by clinicians. There are therefore substantial variations in dietary behaviors of patients and recommendations for them, although clinicians do not routinely endorse specific diets for patients with IBD. Dietary clinical trials have been limited by their inability to include a placebo control, contamination of study groups, and inclusion of patients receiving medical therapies. Further challenges include accuracy of information on dietary intake, complex interactions between foods consumed, and differences in food metabolism among individuals. We review the roles of diet in the etiology and management of IBD, based on plausible mechanisms and clinical evidence. Researchers have learned much about the effects of diet on the mucosal immune system, epithelial function, and the intestinal microbiome; these findings could have significant practical implications. Controlled studies of patients receiving enteral nutrition and observations made from patients on exclusion diets have shown that components of whole foods can have deleterious effects for patients with IBD. Additionally, studies in animal models suggested that certain nutrients can reduce intestinal inflammation. In the future, engineered diets that restrict deleterious components but supplement beneficial nutrients could be used to modify the luminal intestinal environment of patients with IBD—these might be used alone or in combination with immunosuppressive agents, or as salvage therapy for patients who do not respond or lose responsiveness to medical therapies. Stricter diets might be required to induce remission, whereas more sustainable exclusion diets could be used to maintain long-term remission.

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“…A review conducted regarding patients suffering from Crohn disease (CD) 9 or ulcerative colitis (UC) concluded that high lipid intake increased the risk of inflammatory bowel diseases (3). Gruber et al (4) showed that high-fat diets (HFDs) intensified CD-like ileitis in TNF DARE/WT mice. Other studies revealed that a high-fat intake increased intestinal inflammation in a CD Multidrug resistance protein 1 a (Mdr1a) 2/2 mouse model (5) and aggravated UC induced by dextran sulfate sodium in mice (6).…”

Section: Introductionmentioning

confidence: 99%