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, R_0.6 (0.6 mg/kg) and R_0.06 (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 (R_0.06 46.7%; R₀ 72%) and esophageal epithelial atrophy (R_0.06 40%; R₀ 44%) in rats, while the R₆ group did not display symptoms (P < 0.001, respectively). Esophageal epithelial atrophy occurred simultaneously (R_0.06 66.7%; R₀ 63.6%) with ariboflavinosis or appeared alone (R_0.06 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.