Fecal metaproteomics reveals alterations in gut microbiota and intestinal proteins in adolescents with bipolar depression

This study aims to compare the gut microbiota and the profiles of human and microbial proteins in adolescents with bipolar depression (BD) and healthy controls (HCs), as well as to investigate the potential of gut-derived proteins as biomarkers for BD diagnosis. Fecal samples were collected from 15 adolescents with depressive episodes of BD and 58 healthy individuals, and fecal metaproteomics was used to assess changes in the gut environment. The results revealed an increased abundance of gut bacteria associated with lactate production and metabolism, such as Bifidobacteriaceae and Megasphaera , in BD patients. Additionally, there was a higher abundance of Alistipes , a bacterium linked to stress. Notably, the host proteins CELA2A, DEFA3, and KLK1 achieved high ROC-AUC values (0.905, 0.897, and 0.897) and PR-AUC values (0.978, 0.975, and 0.975),indicating their potential as diagnostic biomarkers for BD. In conclusion, we observed an increased abundance of Bifidobacteriaceae, Megasphaera , and Alistipes in adolescents with BD. We propose that CELA2A, DEFA3, and KLK1 could be potential biomarkers for BD, although further validation is required.