Patients with inflammatory bowel disease (IBD) may benefit from biotin supplementation, according to a preclinical study.
In mice, biotin supplementation delayed onset of colitis, minimized pathology, and accelerated healing, reported lead author Jonathan Skupsky, MD, of the University of California, Irvine, and colleagues.
“Biotin deficiency often is overlooked in the setting of IBD and there have been several reports of biotin deficiency in patients with IBD,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.
In addition to these clinical reports, Dr. Skupsky and colleagues were motivated by their previous research, which showed that, in mice, knockout of the sodium-dependent multivitamin transporter (SMVT) for intestinal biotin uptake led to intestinal inflammation and dysplasia, thereby adding evidence that IBD and biotin could be linked.
In the present study, the investigators first compared mice fed a biotin-deficient diet with those fed a biotin-rich diet. Mice lacking biotin developed alopecia and weight loss within 7 weeks, and over time, stool that was soft and bloody. At week 14, mice fed the biotin-deficient diet had intestinal inflammation, based on elevated fecal calprotectin levels. In contrast, mice fed a biotin-rich diet had no gastrointestinal pathology.
“Although no mouse model entirely recapitulates patients with IBD, this model reproduces many of the findings including weight loss, bloody diarrhea, increased fecal calprotectin, altered crypt architecture, and infiltration of neutrophils and lymphocytes to the mucosa and submucosa,” the investigators wrote.
After this experiment, another group of mice were given drinking water with 3% dextran sodium sulfate (DSS), which induced severe colitis within 7 days. The distal colons of these mice had reduced expression of SMVT, the biotin transporter. This finding was also observed in biopsy samples from patients with ulcerative colitis, suggesting a shared pathway.
“This raises the possibility that [the biotin transport pathway] could be a target for therapy,” the investigators wrote.
Next the investigators tested the effect of prophylactic biotin supplementation in mice receiving 1.5% DSS in drinking water. Compared with mice that went without biotin, those that received a week of supplementation before DSS challenge had delayed, milder colitis, with histologic findings and fecal calprotectin levels that approximated those of healthy controls.
In a similar experiment, two groups of mice were given DSS for 7 days, then water or water plus biotin. Those in the biotin group recovered faster and more completely, again with clinical and histologic findings that was close to controls.
According to the investigators, these findings suggest that biotin may be able to protect against development of colitis and speed healing during early remission.
Further experiments dove deeper into cellular processes and molecular mechanisms, ultimately revealing that biotin supplementation reduced activation of NF-kappaB, which led to decreased intestinal permeability and inflammatory cytokines.
“The specific mechanism(s) linking biotin and NF-kappaB is unclear but could be mediated via the different cellular pathways that are affected by biotin availability,” the investigators wrote.
They noted that IBD is a complex condition, which can make it difficult to accurately model the disease; however, they also suggested that the findings are compelling enough to prompt further investigation in human patients because biotin could be a convenient therapeutic add-on.
“We are optimistic that the data presented here will serve as the foundation for future clinical studies to determine if biotin supplementation should be used as adjunct therapy in IBD,” the investigators wrote. “Biotin is available over the counter, is affordable, and it has minimal side effects, making it an ideal therapeutic if clinical trials can show similar efficacy to what we have seen in this preclinical model.
The study was funded by the Veteran’s Administration and the National Institutes of Health. The investigators reported no conflicts of interest.
SOURCE: Skupsky J et al. Cell Mol Gastroenterol Hepatol. 2019 Nov 28. doi: 10.1016/j.jcmgh.2019.11.011.
