Protective Mechanisms of Butyrate on Inflammatory Bowel Disease

Silva, João P.B.; Navegantes-Lima, Kely Campos; Oliveira, Ana Lígia de Brito; Rodrigues, Dávila Valentina Silva; Gaspar, Sílvia L.F.; Monteiro, Valter V S; Moura, Davi P.; Monteiro, Marta Chagas

doi:10.2174/1381612824666181001153605

Cited by 100 publications

(64 citation statements)

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“…The results showed that butyrate was significantly decreased in HIF‐1α ΔIEC mice compared with that of WT mice (Figure 3E). It is well‐known that butyrate plays an important protective role in intestinal homoeostasis through both adaptive immunity and innate immunity (Silva et al, 2018). Finally, we aimed to determine whether butyrate could regulate the expression of ZO‐1 and Occludin protein in Caco‐2 cells.…”

Section: Resultsmentioning

confidence: 99%

“…In our study, we observed a substantial reduction in butyrate in HIF‐1α ΔIEC mice from what was observed in WT mice. Butyrate has been reported to play an important protective role in DSS‐induced colitis by activating regulatory T cells, increasing the acetylation of histones and decreasing the activation of nuclear factor‐κB (Silva et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Mutual regulation between butyrate and hypoxia‐inducible factor‐1α in epithelial cell promotes expression of tight junction proteins

Yin

Zhou

Yang

et al. 2020

Cell Biology International

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Inflammatory bowel disease is a kind of multi-aetiological chronic disease that is driven by multidimensional factors. Hypoxia-inducible factor-1α (HIF-1α) plays an important role in anti-inflammatory and cellular responses to hypoxia. Previous studies have found that B or T-cell-specific HIF-1α knock out mice exhibit severe colonic inflammation. However, we know very little about other functions of HIF-1α in intestinal epithelial cells (IECs). In our study, HIF-1α ΔIEC mice were used to study the function of HIF-1α in IECs. HIF-1α was knocked down in Caco-2 cells by transfection with a small interfering (si) RNA. Immunohistochemical staining and western blotting were used to detect the expression of zonula occluden-1 (ZO-1) and Occludin. The content of colon was harvested for high-performance liquid chromatography analysis to examine the levels of butyrate in the gut. Our research found that HIF-1α played a protective role in dextran sulphate sodium-induced colitis, which was partly due to its regulation of tight junction (TJ) protein expression. Further study revealed that HIF-1α mediated TJ proteins levels by moderating the content of butyrate. Moreover, we found that butyrate regulated TJ protein expression, which is dependent on HIF-1α. These results indicated that there is a mutual regulatory mechanism between butyrate and HIF-1α, which has an important role in the maintenance of barrier function of the gastrointestinal tract.Abbreviations: CD, Crohn's disease; HIF-1α, hypoxia-inducible factor-1α; HPLC, high-performance liquid chromatography; IBD, inflammatory bowel disease; IEC, intestinal epithelial cell; IHC, immunohistochemical; UC, ulcerative colitis; ZO-1, zonula occluden-1 Jiuheng Yin and Chao Zhou are co-first authors.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mutual regulation between butyrate and hypoxia‐inducible factor‐1α in epithelial cell promotes expression of tight junction proteins

Yin

Zhou

Yang

et al. 2020

Cell Biology International

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“…In particular, administration of butyrate in mice treated with the chemotherapeutic drug 5-fluorouracil resulted in reduced inflammation and improved cell integrity [27,28]. While insightful, few studies have been able to provide mechanistic insight, simply reporting GI-M related consequences including inflammation and barrier integrity [27,29].…”

Section: Discussionmentioning

confidence: 99%

Development of a self-limiting model of Methotrexate-induced mucositis reinforces butyrate as a potential therapy

Ferreira

Wehkamp

et al. 2020

Preprint

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Background: Gastrointestinal mucositis remains a significant complication of anticancer treatment, with limited anti-mucositis interventions. Currently, there are few validated in vitro systems suitable to study the mechanisms of mucosal injury. Therefore, we aimed to develop and characterize a chemotherapeutic-induced model of mucositis using 3D intestinal organoids. Methods: Organoids derived from mouse ileum were grown for 7 days and incubated with different concentrations of the chemotherapeutic agent methotrexate (MTX), ranging from 0-1000 ng/ml. Metabolic activity, citrulline levels and cytokine/chemokine production were measured to determine the optimal dosage and incubation time. To link the model to clinical practices, the protective effects of folinic acid on the toxicity of MTX were investigated by pre-treating organoids with (0.0005-50 µg/mL) folinic acid. Given the impact of microbial-derived short-chain fatty acids in epithelial health, we also evaluated the impact of short-chain fatty acid supplementation on MTX toxicity in the organoid model. Results: MTX treatment caused a dose-dependent reduction in cell metabolic activity and citrulline production. Folinic acid treatment reduced MTX toxicity when applied simultaneously or up to 24 hours after treatment. Supplementation of the growth medium with butyrate reduced MTX toxicity. Analysis of organoid gene expression suggests that butyrate may reduce intracellular MTX concentrations by increasing the expression of MTX transporters, including the ABCC1 transporter.Conclusion: MTX causes significant organoid damage, which can be reversed upon removal of MTX. The specific readouts and the protective effects of folinic acid suggest that the model is clinically relevant, and can be used in the future to study mucositis, diminishing the need for animal models. By using the model for intervention, it was found that prophylactic treatment with butyrate might be a valuable strategy for prophylactic mucositis prevention.

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“…Butyrate, probably the most important SCFA, influences both the adaptive and the innate immunity, regulating the activation of regulatory T cells, and decreasing the activation of NF-KB. Butyrate, also, increases the mucus production and the rearrangement of tight junction proteins [97].…”

Section: Short Chain Fatty Acids (Scfas)mentioning

confidence: 98%

Enteral Nutrition Supplemented with Transforming Growth Factor-β, Colostrum, Probiotics, and Other Nutritional Compounds in the Treatment of Patients with Inflammatory Bowel Disease

2020

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Enteral nutrition seems to play a significant role in the treatment of both adults and children with active Crohn’s disease, and to a lesser degree in the treatment of patients with active ulcerative colitis. The inclusion of some special factors in the enteral nutrition formulas might increase the rate of the efficacy. Actually, enteral nutrition enriched in Transforming Growth Factor-β reduced the activity index and maintained remission in patients with Crohn’s disease. In addition, a number of experimental animal studies have shown that colostrum exerts a significantly positive result. Probiotics of a special type and a certain dosage could also reduce the inflammatory process in patients with active ulcerative colitis. Therefore, the addition of these factors in an enteral nutrition formula might increase its effectiveness. Although the use of these formulas is not supported by large clinical trials, it could be argued that their administration in selected cases as an exclusive diet or in combination with the drugs used in patients with inflammatory bowel disease could benefit the patient. In this review, the authors provide an update on the role of enteral nutrition, supplemented with Transforming Growth Factor-β, colostrum, and probiotics in patients with inflammatory bowel disease.

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Protective Mechanisms of Butyrate on Inflammatory Bowel Disease

Cited by 100 publications

References 0 publications

Mutual regulation between butyrate and hypoxia‐inducible factor‐1α in epithelial cell promotes expression of tight junction proteins

Mutual regulation between butyrate and hypoxia‐inducible factor‐1α in epithelial cell promotes expression of tight junction proteins

Development of a self-limiting model of Methotrexate-induced mucositis reinforces butyrate as a potential therapy

Enteral Nutrition Supplemented with Transforming Growth Factor-β, Colostrum, Probiotics, and Other Nutritional Compounds in the Treatment of Patients with Inflammatory Bowel Disease

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