Association of birth weight with lung function and the mediating role of gut microbiota: A STROBE 2-step Mendelian randomization study

Accumulating evidence has suggested that low birth weight (LBW) influences lung function deficit in adulthood. The aim of this study was to examine the relationship between LBW and adult lung function deficit and to explore the potential mediating effect of the gut microbiota in this relationship. Using summary data from genome-wide association studies, we applied 2-sample Mendelian randomization to investigate the association between birth weight and adult lung function deficit. Various MR analysis methods were used, including the inverse variance weighted, MR-Egger, weighted median, simple mode and weighted mode. Furthermore, a mediation analysis was performed to identify the potential mediating role of 412 known bacterial microbiota. This study identified significant genetic associations between birth weight and forced vital capacity, forced expiratory volume in 1-s (FEV1), FEV1/forced vital capacity ratio, and lung volume. In addition, a 2-step MR analysis indicated that the effect of LBW on lung function was mediated by specific gut microbiota, including g_Blautia, s_Subdoligranulum_unclassified, and s_Ruminococcus_obeum. LBW is associated with adult lung function deficit, with gut microbiota partially mediating this relationship. These findings provide important insights for the prevention of lung function impairment in individuals with LBW.