Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway

Elahi, Asif; Sabui, Subrata; Narasappa, Nell; Agrawal, Sudhanshu; Lambrecht, Nils; Agrawal, Anshu; Said, Hamid M.

doi:10.4049/jimmunol.1701200

Cited by 44 publications

(49 citation statements)

References 46 publications

(54 reference statements)

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“…34 The mechanisms underlying the pathogenesis of biotin deficiency and biotin's therapeutic potential remains an active area of research and several advances have been made recently. 6,8,13,34,35,39,[47][48][49] We previously reported on an SMVT knockout mouse that provided evidence that the SMVT system is exclusively responsible for intestinal biotin uptake and deletion of SMVT is sufficient to induce colitis. 2 SMVT levels also can decrease physiologically in response to cytokine activation of the NF-kB pathway.…”

Section: Discussionmentioning

confidence: 99%

“…These data complement earlier studies showing that biotin levels can affect innate and adaptive immune responses. 6,[8][9][10]13,35,39 To address whether or not biotin therapy alters mucosal permeability we performed a fluorescein isothiocyanate (FITC)-dextran permeability assay after the induction of remission protocol. We noted increased levels of FITCdextran in the plasma of mice that had received only water after DSS exposure, whereas mice that had received biotin therapy showed similar values to the controls that received no DSS ( Figure 6A).…”

Section: Biotin Therapy Leads To a Reduction In Inflammatory Cytokinementioning

confidence: 99%

“…1 Its classic role is as a covalently bound coenzyme for cytoplasmic carboxylases used in fatty acid homeostasis, gluconeogenesis, and other metabolic pathways, 2 but emerging data also have identified a role in cellular stress response, 3 gene regulation, 4,5 and immune responses. [6][7][8][9][10] Clinically, biotin deficiency, whether induced by dietary means or by mutation of the intestinal biotin uptake system (ie, sodium-dependent multivitamin transporter [SMVT], Slc5a6), is associated with failure to thrive, microcephaly, osteoporosis, immunodeficiency, alopecia, dermatitis, and conjunctivitis. 11,12 In our previous studies to determine the relative contribution of SMVT toward total carrier-mediated biotin absorption, we made the serendipitous finding that SMVT knockout mice also develop colonic crypt abscesses, neutrophil infiltration, submucosal edema, and dysplastic changes.…”

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confidence: 99%

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Biotin Supplementation Ameliorates Murine Colitis by Preventing NF-κB Activation

Skupsky

Sabui

Hwang

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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Biotin deficiency causes an inflammatory bowel disease-like state, but biotin supplementation has never been tested as a therapeutic in established models for inflammatory bowel disease. We found that biotin therapy leads to delayed onset and severity of dextran sodium sulfate colitis mediated by decreased activation of nuclear factor-kB. BACKGROUND & AIMS: Biotin is a water-soluble vitamin that is indispensable for human health. Biotin deficiency can cause failure-to-thrive, immunodeficiency, alopecia, dermatitis, and conjunctivitis. We previously reported that biotin deficiency also can lead to severe colitis in mice, which is completely reversed with supplementation. Our aim in this study was to determine if high-dose biotin supplementation can provide a therapeutic benefit in a preclinical model for inflammatory bowel disease (IBD) and to identify the molecular mechanism by which this occurs. METHODS: Mice were challenged with dextran sodium sulfate to induce colitis and were treated with 1 mmol/L biotin to induce or maintain remission. Clinical response was monitored by the Disease Activity Index and fecal calprotectin levels. The colon tissue was investigated for histology, length, as well as expression of inflammatory cytokines (interleukin 6, tumor necrosis factor-a, interleukin 1b), intestinal permeability, tight junctions (zonula occludens-1 and claudin-2), and the transcription factor nuclear factor-kB (NF-kB). RESULTS: Biotin therapy led to delayed onset and severity of colitis as well as accelerated healing. There was improvement in the Disease Activity Index, fecal calprotectin levels, colon length, and histology. In addition, biotin-treated mice had reduced expression of inflammatory cytokines, reduced intestinal permeability, and reduced activation of NF-kB. CONCLUSIONS: Oral supplementation with biotin provides benefit for maintenance and induction of remission in the dextran sodium sulfate preclinical model for IBD. Biotin does this by reducing the activation of NF-kB, which prevents the production of inflammatory cytokines and helps maintain the integrity of the intestinal barrier. Clinically, the NF-kB pathway is important in the development of IBD and this finding suggests that biotin may have therapeutic potential for patients with IBD.

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Section: Discussionmentioning

confidence: 99%

Section: Biotin Therapy Leads To a Reduction In Inflammatory Cytokinementioning

confidence: 99%

mentioning

confidence: 99%

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Biotin Supplementation Ameliorates Murine Colitis by Preventing NF-κB Activation

Skupsky

Sabui

Hwang

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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“…Vitamin B 7 (biotin) is widely distributed in food items and synthesized in meaningful amounts by gut microflora in humans. Recently it was showed the role of biotin in immune-mediated intestinal inflammation [ 168 ].…”

Section: Vitamins and Human Healthmentioning

confidence: 99%

Challenging microalgal vitamins for human health

et al. 2020

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Background Vitamins’ deficiency in humans is an important threat worldwide and requires solutions. In the concept of natural biofactory for bioactive compounds production, microalgae represent one of the most promising targets filling many biotechnological applications, and allowing the development of an eco-sustainable production of natural bioactive metabolites. Vitamins are probably one of the cutting edges of microalgal diversity compounds. Main text Microalgae can usefully provide many of the required vitamins in humans, more than terrestrial plants, for instance. Indeed, vitamins D and K, little present in many plants or fruits, are instead available from microalgae. The same occurs for some vitamins B (B12, B9, B6), while the other vitamins (A, C, D, E) are also provided by microalgae. This large panel of vitamins diversity in microalgal cells represents an exploitable platform in order to use them as natural vitamins’ producers for human consumption. This study aims to provide an integrative overview on vitamins content in the microalgal realm, and discuss on the great potential of microalgae as sources of different forms of vitamins to be included as functional ingredients in food or nutraceuticals for the human health. We report on the biological roles of vitamins in microalgae, the current knowledge on their modulation by environmental or biological forcing and on the biological activity of the different vitamins in human metabolism and health protection. Conclusion Finally, we critically discuss the challenges for promoting microalgae as a relevant source of vitamins, further enhancing the interests of microalgal “biofactory” for biotechnological applications, such as in nutraceuticals or cosmeceuticals.

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“…Of note, the expression of Foxp3, as well as IL‐10, was found to be decreased in the same biotin‐deficient condition. Thus, the polarization conditions observed during biotin deficiency drive CD4 + T lymphocytes to Th1/Th17 deviation via mTOR signalling pathway in CD4 + T cells during in vitro and in vivo conditions . Moreover, the development of the Th17 phenotype of CD4 + T lymphocytes has been shown to be dependent on aerobic glycolysis stimulated by signalling mTORC1‐HIFα in a hypoxia‐normoxia positive feedback.…”

Section: Th17 Mtorc Pathwaysmentioning

confidence: 99%

Deciphering targets of Th17 cells fate: From metabolism to nuclear receptors

2019

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Evidence indicates that reprogramming of metabolism is critically important for the differentiation of CD4 + T lymphocytes, and the manipulation of metabolic pathways in these cells may shape their fate and function. Distinct subgroups from T lymphocytes, such as Th17, adopt specific metabolic programmes to support their needs. Some important metabolic reactions, such as glycolysis, oxidative phosphorylation, are considered important for the differentiation of these lymphocytes. Since their discovery nearly a decade ago, Th17 lymphocytes have received significant attention because of their role in the pathology of several immune‐mediated inflammatory diseases such as multiple sclerosis. In this review, it will be discussed as the involvement of T cell metabolism and as metabolic reprogramming in activated T cells dictates fate decisions to Th17. The involvement of nuclear receptors such as RORyt e PPARs in the induction of Th17 cells was also discussed. Understanding the metabolic pathways involved in the differentiation of the distinct subgroups of T lymphocytes helps in the design of promising therapeutic proposals.

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Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway

Cited by 44 publications

References 46 publications

Biotin Supplementation Ameliorates Murine Colitis by Preventing NF-κB Activation

Biotin Supplementation Ameliorates Murine Colitis by Preventing NF-κB Activation

Challenging microalgal vitamins for human health

Deciphering targets of Th17 cells fate: From metabolism to nuclear receptors

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