Causality between gut microbiota and gastroesophageal reflux disease: A two-sample Mendelian randomization analysis

Background Studies have provided evidence of alterations in the diversity and composition of the gut microbiota of individuals with Gastroesophageal reflux disease (GERD). However, the causality between gut microbiota and GERD remains uncertain. Methods Summary data on gut microbiota and GERD were obtained from publicly available genetic databases and analyzed by using two sets of genetic instruments. MR analyses were conducted using inverse variance weighted (IVW; primary method for causal inference in TSMR analysis), weighted median, MR Egger, and weighted mode methods. Results TSMR analysis revealed that 8 bacterial taxa, including 4 risk factors and 4 protective factors, were associated with GERD. IVW results showed that the risk of GERD was negatively associated with the family Bifidobacteriaceae (P = 0.026), order Bifidobacteriales (P = 0.002), family Christensenellaceae (P = 0.000), and genus Odoribacter (P = 0.024). Conversely, it was positively associated with the class Mollicutes (P = 0.003), phylum Tenericutes (P = 0.003), family Rikenellaceae (P = 0.015), and genus Prevotella 9 (P = 0.013). Reverse TSMR analysis did not reveal a reverse causal relationship between GERD and gut microbiota. Conclusions We established a causal association between gut microbiota and GERD, thus providing a groundbreaking genetic perspective for studying pathogenesis of GERD and potential strategies for its prevention and treatment.