Riboflavin Deficiency-Induced Angular Stomatitis and Conjunctivitis in Associated with Gut Microbiota Dysbiosis

PurposeRiboflavin deficiency causes ariboflavinosis, and the purpose of this study is to investigate the potential biological factors underlying its occurrence. MethodsMale F344 rats were randomly assigned to R6 and R0 groups. The healthy controls (R6 group) was fed a riboflavin-normal diet (6 mg/kg riboflavin), while the R0 group was fed a riboflavin-deficient diet (0 mg/kg riboflavin) for 16 weeks. Following this period, the R0 group was switched to a riboflavin replenishment diet (6 mg/kg riboflavin) for an additional 4 weeks (weeks 17-20). The bacterial communities were analyzed using high-throughput 16S rRNA gene sequencing. ResultsRiboflavin deficiency induces ariboflavinosis in rats (66.7%), characterized by angular stomatitis and conjunctivitis. With riboflavin replenishment, ariboflavinosis was completely resolved. Riboflavin deficiency altered the gut microbiota co-occurrence network and composition. The potential mechanism is predicted to involve an increase in glycan biosynthesis and metabolism within the gut microbiota, particularly in lipopolysaccharide biosynthesis pathways. ConclusionsThese findings suggest that riboflavin deficiency induces ariboflavinosis by altering the gut microbiota, providing new insights into the mechanisms of riboflavin deficiency and its association with chronic inflammation. Clinical perspectivesRiboflavin is an essential nutrient that must be obtained through the diet, as the human body cannot synthesize it. Since riboflavin is not stored in the body, regular dietary intake is necessary. Riboflavin deficiency is prevalent worldwide and can lead to ariboflavinosis. However, the specific mechanisms underlying riboflavin deficiency-induced ariboflavinosis remain unclear. This study demonstrates that riboflavin deficiency causes ariboflavinosis (characterized by angular stomatitis and conjunctivitis) in rats and reveals a close relationship between riboflavin deficiency and alterations in gut microbiota composition. Gut dysbiosis appears to be a hallmark of ariboflavinosis and may serve as a promising diagnostic biomarker and therapeutic target for the condition.