P668 Does biotin deficiency play a role in the pathogenesis of Inflammatory Bowel Disease? Preliminary results of a cross-sectional study

Background Biotin, a water-soluble B-vitamin, has been shown to have anti-inflammatory properties. A biotin-deficient diet was recently shown to induce a colitis-like phenotype in mice, alleviated by biotin substitution. Mice with DSS colitis showed biotin deficiency and significantly reduced levels of SDMT, a protein involved in biotin absorption. Oral biotin substitution reversed DSS colitis and induced remission by inhibiting NF-κB, a transcription factor that hinders inflammatory cytokine expression and plays a role in intestinal barrier integrity and IBD. We investigated for the first time a possible clinical role of biotin status in IBD. Methods In a comparative, cross-sectional study, serum samples of IBD patients were compared with samples of 80 healthy blood donors (40f;18-65y). CBC, albumin and hsCRP were determined by standard tests and samples assessed for presence/absence of inflammation (serum hsCRP, cutoff <5mg/L). Since its known that serum biotin levels does not accurately reflect biotin status, serum 3-hydroxyisovaleryl carnitine (3HIAc) levels were determined by LC-MS/MS. Results 138 IBD patients (67f;72 CD/66 UC;42.5±14.3y) were enrolled. Of these, 83/138 had inflammation (39f;43CD/40UC;42.5±14.6y) and 55/138 no inflammation (28f;29CD/26UC;42.5±13.9y). In IBD patients, mean serum 3HIAc levels were significantly higher vs. controls but similar with vs. without inflammation (Table 1). The reference serum 3HIAc level was calculated as 11.0–27.3 nmol/L from controls; biotin deficiency was defined as >27.3 nmol/L 3HIAc (90thPC), since no validated cut-off exists. Biotin deficiency in IBD patients was significantly greater than in controls (Table 1). Conclusion High serum 3HIAc levels were associated with IBD. In line with preclinical studies, biotin deficiency was more pronounced in IBD patients than controls. No relation was found with inflammatory activity or disease type. Our findings suggest that biotin may have a bigger role than thought in IBD; whether as a cause or effect in IBD pathogenesis warrants investigation. Routine assessment and correction of biotin status may ameliorate IBD and help maintain intestinal integrity. Table 1: 3-hydroxyisovaleryl carnitine levels and biotin deficiency

Dietary Opinion Beyond Biotin Intakes

: Biotin (Vitamin-H) intake is usual in individuals taking balanced diet on regular basis as biotin is present in common dietary substances. Regarding its intakes some recommendations must be keep in mind in order to avoid any inconvenience. Although biotin deficiency is rare but may occur under some special circumstances. Biotin creates hindrance in results of many medical tests reports so while taking biotin as diet or supplements, your consultant should aware of your biotin intakes. Some specific diseased conditions can be avoided only by excessive biotin intakes in dietary forms also.

Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model

Mitochondrial and metabolic dysfunction are often implicated in neurological disease, but effective mechanism-based therapies remain elusive. We performed a genome-scale forward genetic screen in a Drosophila model of tauopathy, a class of neurodegenerative disorders characterized by the accumulation of the protein tau, and identified manipulation of the B-vitamin biotin as a potential therapeutic approach in tauopathy. We show that tau transgenic flies have an innate biotin deficiency due to tau-mediated relaxation of chromatin and consequent aberrant expression of multiple biotin-related genes, disrupting both carboxylase and mitochondrial function. Biotin depletion alone causes mitochondrial pathology and neurodegeneration in both flies and human neurons, implicating mitochondrial dysfunction as a mechanism in biotin deficiency. Finally, carboxylase biotin levels are reduced in mammalian tauopathies, including brains of human Alzheimer’s disease patients. These results provide insight into pathogenic mechanisms of human biotin deficiency, the resulting effects on neuronal health, and a potential therapeutic pathway in the treatment of tau-mediated neurotoxicity.

40 PRLR and PCCA variants associated with hair length in Brangus heifers

Thermal stress limits beef cattle production and results in a loss of $370 million in the U.S. annually due to reduced animal performance. A shorter hair coat is a key thermoregulative adaptation that allows cattle to lose heat more efficiently through conductive, convective, and evaporative cooling at the hair-skin interface. The objective of this study was to identify genetic variants associated with the length of the topcoat and undercoat of cattle. Hair samples were collected from the shoulder, 4 inches down from the spine from 2,161 heifers in 2016, 2017 and 2018. ImageJ software was used to measure hair length. The length of the topcoat and undercoat were evaluated for each individual by averaging five long and five short hairs, respectively. DNA was extracted from blood samples and genotyped with the Bovine GGP F250 array. After quality control, 132,225 SNP were available for association analyses using Golden Helix SVS. Year of collection was fitted as a fixed effect and the genomic relationship matrix was fitted to account for the genetic covariance among animals. To correct for multiple tests, the Benjamini-Hochberg false discovery rate was constrained to 0.1. Four SNP in the PRLR gene were significantly associated with topcoat length, including a missense mutation that explained 4% of the variation in topcoat length. PRLR has previously been demonstrated to significantly impact hair length in cattle. Seven SNP in the PCCA gene were significantly associated with undercoat length. PCCA belongs to the biotin transport and metabolism pathway. Biotin deficiency has been reported to cause hair loss. These genetic variants may contribute to a shorter hair coat and more thermotolerant animals.

The role of biotin metabolism in the COVID-19 infection

COVID-19 pandemic has become the major health problem in 2020 worldwide and no treatment or cure has been developed until now, however medical doctors use approved anti-viral drugs alone or in combination to treat patients infected by COVID-19. Thus, the outcome and the information of the applied treatments are changing daily basis. One of the changes in the COVID-19 patients has been depilation of the eyebrow and eyelashes. Biotin is a vital cofactor for biotin-dependent enzymes for fatty acids, amino acids, and glucose metabolism. It is known that, biotin deficiency may cause loss of hair, eyebrows and eyelashes. However, either COVID-19 infection or treatment against to cure this infection cause impairment in the biotin metabolism that should be further investigated to better understand possible mechanisms behind the COVID-19 infection and outcomes of the treatment approach to treat it.

Tamoxifen-induced, intestinal-specific deletion of Slc5a6 in adult mice leads to spontaneous inflammation: involvement of NF-κB, NLRP3, and gut microbiota

The sodium-dependent multivitamin transporter (SMVT; SLC5A6) is involved in intestinal absorption of vitamin B7 (biotin). We have previously shown that mice with an embryonic intestinal-specific SMVT knockout (KO) develop biotin deficiency and severe spontaneous intestinal inflammation in addition to growth retardation, developmental delays, and death within the first 6–7 wk of life. The profound morbidity and mortality associated with the SMVT-KO has limited our ability to further characterize the intestinal inflammation and other sequelae of this deletion in adult mice with a mature gut microbiota. To overcome this limitation, we generated an intestine-specific, tamoxifen-inducible, conditional SMVT-KO (SMVT-icKO). Our results showed that adult SMVT-icKO mice have reduced body weight, biotin deficiency, shorter colonic length, and bloody diarrhea compared with age- and sex-matched control littermates. All SMVT-icKO mice also developed spontaneous intestinal inflammation associated with induction of calprotectin (S100a8/S100a9), proinflammatory cytokines (IL-1β, TNF-α, IFN-γ, and IL-6), and an increase in intestinal permeability. Additionally, the intestines of SMVT-icKO showed activation of the NF-κB pathway and the nucleotide-binding domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammasome. Notably, administration of broad-spectrum antibiotics reduced lethality and led to normalization of intestinal inflammation, proinflammatory cytokines, altered mucosal integrity, and reduced expression of the NLRP3 inflammasome. Overall, these findings support our conclusion that the biotin transport pathway plays an important role in the maintenance of intestinal homeostasis, and that NF-κB and the NLRP3 inflammasome, as well as gut microbiota, drive the development of intestinal inflammation when SMVT is absent. NEW & NOTEWORTHY This study demonstrates that deletion of the intestinal biotin uptake system in adult mice leads to the development of spontaneous gut inflammation and that luminal microbiota plays a role in its development.