Biotin Supplementation Ameliorates Murine Colitis by Preventing NF-κB Activation

Abstract

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.

Micronutrient Deficiency in Inflammatory Bowel Diseases: Cause or Effect?

“…In the current study, 6 the authors showed that biotindeficient diet was able to induce a colitis like phenotype in mice, which was alleviated with biotin supplementation. In addition, dextran sulfate sodium (DSS)-induced colitis mice also showed biotin deficiency along with significantly reduced levels of sodium-dependent multivitamin transporter (SMVT) involved in biotin absorption.…”

“…5 Deficiency of vitamins in B complex, specifically thiamine (B1) and biotin, were suggested to be potential culprits in the development of this symptom. 5 In the current issue of Cellular and Molecular Gastroenterology and Hepatology, Skupsky et al 6 provide novel evidence of the role of biotin in UC. Biotin, also known as vitamin B7 or H, is not synthesized in humans; therefore, dietary intake and bacterial synthesis in the gut are its main sources.…”

“…Furthermore, supplementation of biotin (1 mM) via oral administration in mice reversed DSS colitis and also induced remission in the same model. 6 Additionally, the authors demonstrated that biotin deficiency resulted in stimulation of the nuclear factor-kB pathway, resulting in colonic inflammation. Also, biotin supplementation during DSS colitis abrogated nuclear factor-kB activation.…”

What We Know So Far about the Metabolite-Mediated Microbiota-Intestinal Immunity Dialogue and How to Hear the Sound of This Crosstalk

“…Notably, its possible involvement in the NF-κB pathway regulation holds high expectations in a potential antiinflammatory process. Recently, this hypothesis has been strengthened by Skupsky et al, which showed a lowered NF-κB activity and histological signs of mucosal inflammation in the colon of biotin-supplemented mice [ 128 ]. This observation concurs with a previously mentioned study, exploring the supplementation of VB5 and VB8 [ 110 ].…”

Cellular and molecular mediators of lymphangiogenesis in inflammatory bowel disease

“…After stimulation through TLRs, proinflammatory cytokines or antigen receptors, I-κB is phosphorylated, ubiquitinated, and finally proteolytically degraded, leading to de-repression of NF-κB, which rapidly translocate to the nucleus and activates the transcription of several target genes [ 112 ]. It has also been thoroughly established that intestinal inflammation occurring in IBD is accompanied by an NF-κB driven overexpression of pro-inflammatory adhesion molecules and mediators, leading to disturbances in mucosal immunity [ 113 , 114 ].…”