Dynamic interactions between gut microbiome and host lipidome in antenatal depression: a large longitudinal study

Temporal alterations in the host lipidome and gut microbiome, and their dynamic interactions, in the progression of antenatal depression remain poorly understood. Here, we characterized the maternal lipidome and gut microbiome in 1086 Chinese pregnant women from the Tongji-Huaxi-Shuangliu Birth Cohort using 2954 serum and 2812 fecal samples collected longitudinally across early, mid, and late pregnancy. Our analyses identified 95 host lipids, and seven gut microbial genera associated with antenatal depression. Period-specific and longitudinal analyses indicated that lysophosphatidylethanolamines (LPEs) exhibited concordant associations with antenatal depression. In addition, temporal analyses suggested that decreases in the abundances of gut microbial genera [Ruminococcus]_gnavus_group and Enterococcus preceded the onset of antenatal depression and demonstrated extensive associations with LPEs and acylcarnitines (CARs). Integrative analyses revealed bidirectional concurrent and temporal crosstalk between microbiota-lipid axis and antenatal depression, with LPEs and medium- and long-chain CARs constituting key molecules of this axis. Collectively, this study offers valuable insights into the interplay between host lipidome and gut microbiome in the development of antenatal depression, laying a foundation for future investigations into the microbiota-lipid axis during pregnancy.