Ketogenic diet aggravates colitis, impairs intestinal barrier and alters gut microbiota and metabolism in DSS-induced mice

Li, Shengjie; Zhuge, Aoxiang; Wang, Kaicen; Lv, Longxian; Bian, Xiaoyuan; Yang, Liya; Xia, Jiafeng; Jiang, Xianwan; Wu, Wenrui; Wang, Zhen; Wang, Qiangqiang; Li, Lanjuan

doi:10.1039/d1fo02288a

Cited by 53 publications

(37 citation statements)

References 50 publications

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“…Additionally, the severity index of colitis measured by DAI scores was also decreased by ADMSCs transplantation (Figure 2C). Another typical morphological alteration in colitis mice is reductions in colon length (33). In this work, we found that the colon lengths of mice in the ADMSCs +DSS group were approximated to those in the control group, while mice in the DSS group exhibited significant reductions in colon length (Figure 2D).…”

Section: Admscs Transplantation Ameliorated Dss-induced Colitis and I...supporting

confidence: 54%

Adipose-Derived Mesenchymal Stem Cells Reprogram M1 Macrophage Metabolism via PHD2/HIF-1α Pathway in Colitis Mice

Yuan

Zhuge

et al. 2022

Front. Immunol.

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Ulcerative colitis (UC) is a chronic inflammatory bowel disease worldwide. Infiltration of pro-inflammatory macrophages (M1 macrophages) contributes to the occurrence of bowel inflammation. Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic strategy for UC, but the exact mechanism remains unknow yet. Here, we treated DSS-induced colitis mice with adipose‐derived mesenchymal stem cells (ADMSCs) and revealed that ADMSCs alleviated colon inflammation by reducing the infiltration of M1 macrophages. Moreover, ADMSCs exerted this therapeutic effect by inhibiting succinate accumulation, increasing PHD2 to prevent M1 macrophages from overexpressing HIF-1α and thereby reprogramming the glycolytic pathway of M1 macrophages. Meanwhile, the succinate secreted by M1 macrophages triggered ADMSCs to secrete PGE2 in return, which could also shift macrophages from M1 phenotype to M2. Our work demonstrated an immunomodulatory effect of ADMSCs and provided a novel perspective on UC therapy.

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Section: Admscs Transplantation Ameliorated Dss-induced Colitis and I...supporting

confidence: 54%

Adipose-Derived Mesenchymal Stem Cells Reprogram M1 Macrophage Metabolism via PHD2/HIF-1α Pathway in Colitis Mice

Yuan

Zhuge

et al. 2022

Front. Immunol.

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“…KD alters the gut microbiota in a manner different from a high-fat diet and elevates circulating ketone bodies, which inhibit the growth of Bifidobacterium and reduce the level of intestinal pro-inflammatory Th17 cells [ 179 ]. However, in another study, KD was found to aggravate DSS-induced colitis with increased pathogenic bacteria such as Proteobacteria , Enterobacteriaceae , Helicobacter and Escherichia–Shigella and decreased potentially beneficial Erysipelotrichaceae [ 180 ]. Moreover, the actual role of the KD on human beings with IBD remains unknown, and the health effects of long-term KD also require further studies.…”

Section: Dietary Strategies Alleviating Ibdmentioning

confidence: 99%

Dietary Patterns and Gut Microbiota Changes in Inflammatory Bowel Disease: Current Insights and Future Challenges

Yan

Lei

et al. 2022

Nutrients

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Inflammatory bowel disease (IBD) is a result of a complex interplay between genes, host immune response, gut microbiota, and environmental factors. As one of the crucial environmental factors, diet plays a pivotal role in the modulation of gut microbiota community and the development of IBD. In this review, we present an overview of dietary patterns involved in the pathogenesis and management of IBD, and analyzed the associated gut microbial alterations. A Westernized diet rich in protein, fats and refined carbohydrates tends to cause dysbiosis and promote IBD progression. Some dietary patterns have been found effective in obtaining IBD clinical remission, including Crohn’s Disease Exclusion Diet (CDED), Mediterranean diet (MD), Anti-Inflammatory Diet (AID), the low-“Fermentable Oligo-, Di-, Mono-saccharides and Polyols” (FODMAP) diet, Specific Carbohydrate Diet (SCD), and plant-based diet, etc. Overall, many researchers have reported the role of diet in regulating gut microbiota and the IBD disease course. However, more prospective studies are required to achieve consistent and solid conclusions in the future. This review provides some recommendations for studies exploring novel and potential dietary strategies that prevent IBD.

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“…Researchers found that the KD significantly reduced inflammatory responses, protected intestinal barrier function, reduced innate lymphoid cell (ILC3) production, and reduced expression of related inflammatory cytokines as compared to LCD [ 66 ]. While the Kong et al study [ 66 ] suggested that a KD attenuated intestinal inflammation in a DSS murine colitis model, another study [ 67 ] showed the opposite findings. The Li et al study [ 67 ] aimed at exploring the effects of a ketogenic diet on IBD in mice and its potential mechanisms; mouse models were given a KD or a control diet (CD) for a month and IBD was induced by diluting drinking water with 2% DSS during the last week of the diet.…”

Section: Specific Dietary Interventionsmentioning

confidence: 99%

Dietary Exposures and Interventions in Inflammatory Bowel Disease: Current Evidence and Emerging Concepts

et al. 2023

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Diet is intimately linked to the gastrointestinal (GI) tract and has potent effects on intestinal immune homeostasis. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the GI tract. The therapeutic implications of diet in patients with IBD have received significant attention in recent years. In this review, we provide a contemporary and comprehensive overview of dietary exposures and interventions in IBD. Epidemiological studies suggest that ultra-processed foods, food additives, and emulsifiers are associated with a higher incidence of IBD. Exclusion and elimination diets are associated with improved symptoms in patients with IBD, but no effects on objective markers of inflammation. Specific dietary interventions (e.g., Mediterranean, specific carbohydrate, high fiber, ketogenic, anti-inflammatory diets) have been shown to reduce symptoms, improve inflammatory biomarkers, and quality of life metrics to varying degrees, but these studies are limited by study design, underpowering, heterogeneity, and confounding. To date, there is no robust evidence that any dietary intervention alone may replace standard therapies in patients with IBD. However, diet may play an adjunct role to induce or maintain clinical remission with standard IBD therapies. The results of novel dietary trials in IBD such as personalized fiber, intermittent fasting, and time-restricted diets are eagerly awaited.

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Ketogenic diet aggravates colitis, impairs intestinal barrier and alters gut microbiota and metabolism in DSS-induced mice

Abstract: A ketogenic diet was shown to aggravate DSS-induced colitis in mice by increasing intestinal and systemic inflammation, and disrupting the intestinal barrier, which results from modulated gut microbiota and metabolism.

Cited by 53 publications

References 50 publications

Adipose-Derived Mesenchymal Stem Cells Reprogram M1 Macrophage Metabolism via PHD2/HIF-1α Pathway in Colitis Mice

Adipose-Derived Mesenchymal Stem Cells Reprogram M1 Macrophage Metabolism via PHD2/HIF-1α Pathway in Colitis Mice

Dietary Patterns and Gut Microbiota Changes in Inflammatory Bowel Disease: Current Insights and Future Challenges

Dietary Exposures and Interventions in Inflammatory Bowel Disease: Current Evidence and Emerging Concepts

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