Dietary riboflavin deficiency induces ariboflavinosis and esophageal epithelial atrophy in association with modification of gut microbiota in rats.

PURPOSE: Riboflavin deficiency causes ariboflavinosis, a common nutritional deficiency disease. The purpose of this study is to investigate the effects of riboflavin deficiency on the important internal organs and its potential mechanisms. METHODS: Experiment 1, male F344 rats were randomly assigned to R6 (normal riboflavin, 6 mg/kg) and R0 (riboflavin-deficient, 0 mg/kg) groups. Experiment 2 rats were assigned to R6, R0.6 (0.6 mg/kg) and R0.06 (0.06 mg/kg) groups. Experiment 3 rats were assigned to R6 and R0 → R6 (riboflavin replenishment) groups. Bacterial communities were analyzed based on 16S rRNA gene sequencing. RESULTS: Riboflavin deficiency induced ariboflavinosis (R0.06 46.7%; R0 72%) and esophageal epithelial atrophy (R0.06 40%; R0 44%) in rats, while the R6 group did not display symptoms (P < 0.001, respectively). Esophageal epithelial atrophy occurred simultaneously (R0.06 66.7%; R0 63.6%) with ariboflavinosis or appeared alone (R0.06 33.3%; R0 36.4%). Esophagus is the most vulnerable internal organ. Riboflavin deficiency followed by replenishment (R0 → R6) was effective in treating ariboflavinosis (83.3% vs. 0%, P < 0.001) and esophageal epithelial atrophy (66.7% vs. 20%, P = 0.17). Riboflavin deficiency modulated gut microbiota composition. The several key genera (Romboutsia, Turicibacter and Clostridium sensu stricto 1) were strongly correlated with ariboflavinosis and esophageal epithelial atrophy (P < 0.01 or P < 0.05). The potential mechanism is that gut microbiota affects body's xenobiotic biodegradation and metabolism, and genomic instability. CONCLUSIONS: Riboflavin deficiency induces ariboflavinosis and esophageal epithelial atrophy by modulating the gut microbiota, and offers new Queryinsight into riboflavin deficiency and esophageal lesions.

Dietary riboflavin deficiency induces genomic instability of esophageal squamous cells that is associated with gut microbiota dysbiosis in rats.

SCOPE: Epidemiologic evidence suggests that riboflavin (RBF) deficiency is a specific nutritional predisposition for esophageal cancer. The aim of this study is to investigate the potential roles of gut microbiota in esophageal tumorigenesis caused by the RBF deficiency. METHODS: Male F344 rats were subcutaneously injected with the chemical carcinogen N-nitrosomethylbenzylamine (NMBA, 0.35 mg kg-1). Rats were assigned to 4 groups, denoted as R6 (normal RBF, 6 mg kg-1), R6N (normal RBF combined with NMBA), R6N → R0N (normal RBF conversion to RBF-deficiency), and R0N → R6N (RBF-deficiency conversion to normal RBF). Bacterial communities were analyzed based on high-throughput 16S rRNA gene sequencing. Oxidative DNA damage and double-strand break markers were studied by immunohistochemistry. RESULTS: The R6N → R0N diet enhanced the incidence of esophageal intraepithelial neoplasia (EIN, 40 weeks 66.7% vs. 25 weeks 16.7%, P < 0.05). RBF deficiency and replenishment modulated the gut microbiota composition. The gut microbiota (e.g. Caulobacteraceae, Sphingomonas and Bradyrhizobium) affected xenobiotic biodegradation and the genomic instability of the host. Furthermore, the RBF deficiency aggravated oxidative DNA damage and DNA double-strand breaks (immunohistochemistry) in the esophageal epithelium, whereas the RBF replenishment had the opposite effect (P < 0.05, respectively). CONCLUSIONS: RBF deficiency promotes NMBA-induced esophageal tumorigenesis, which is associated with gut microbiota-associated genomic instability, and offers new insights into the role of RBF deficiency in esophageal carcinogenesis.

Correction: Dietary riboflavin deficiency induces genomic instability of esophageal squamous cells that is associated with gut microbiota dysbiosis in rats.

Correction for 'Dietary riboflavin deficiency induces genomic instability of esophageal squamous cells that is associated with gut microbiota dysbiosis in rats' by Feng Pan et al., Food Funct., 2020, DOI: .

Decreased plasma riboflavin is associated with poor prognosis, invasion, and metastasis in esophageal squamous cell carcinoma.

BACKGROUND: Riboflavin deficiency confers a predisposition for esophageal cancer. The role of plasma riboflavin levels in development and prognosis of individuals with digestive tract inflammation and ulcer (DTIU), digestive tract polyps (DTPs), and ESCC is not well understood. METHODS: We performed a cross-sectional study, including 177 DTIU, 80 DTP, and 324 ESCC cases, to measure the plasma riboflavin levels among the three populations. Correlation between plasma riboflavin levels (categorized as ≥31.8, 6.5-31.8 and ≤6.5 nmol/L groups) and clinical characteristics, as well as survival of ESCC patients (556 cases) was analyzed. RESULTS: There was no difference in plasma riboflavin levels between DTIU, DTP, and ESCC cases (P > 0.05). Plasma riboflavin levels were inversely correlated with invasive depth (correlation coefficient = -0.09, P = 0.026) and lymph node metastasis (correlation coefficient = -0.11, P = 0.010) of ESCC, and ESCC patients with low riboflavin levels had poor recurrence-free survival (P = 0.035) and overall survival (P = 0.003). Decreased riboflavin was a prognostic factor for poor overall survival (HR = 1.91, 95% CI = 1.19-3.07, P = 0.007). CONCLUSIONS: Plasma riboflavin levels in DTIU, DTP, and ESCC patients are similar. Plasma riboflavin levels are associated with the development and prognosis of ESCC.