Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in bipolar disorder with current major depressive episode patients.

Abstract Background The microbiome-gut-brain axis, especially the microbial tryptophan biosynthesis and metabolism pathway (MiTBamp), may is closely connected to with bipolar disorder with current major depressive episode (BPD). Methods We performed the shotgun metagenomics sequencing (SMS) of faecal samples from 25 BPD patients and 28 healthy controls (HCs). Except for the microbiota taxa and the MiTBamp analyses, we also built a classification model using the Random Forests (RF) and Boruta algorithm to find the microbial biomarkers for BPD. Results Compared with the to HCs, the phylum Bacteroidetes abundance was significantly reduced, whereas that of the Actinobacteria and Firmicutes were significantly increased in the BPD patients. We also identified 38 species increased and 6 species decreased significantly in the BPD group. In the MiTBamp, we identified that two Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K00658 and K00837) were significantly lower in the BPD, and five KOs (K01696, K00382, K00626, K01667, and K03781) were significantly higher in the BPD group. and We also identified significant genera and species which were closely related to these KOs. Finally, RF classification based on the gut microbiota at the genus level can achieve an area under the receiver operating characteristic curve of 0.997. Limitations The features of cross-sectional design, limited medicated-sample limited sample size, the heterogeneity of bipolar disorders, and the a lack of serum/plasma tryptophan concentration measurements. Conclusions The present findings enable a better understanding of changes in gastrointestinal microbiome and MiTBamp in BPD. Alterations of the microbes may have the potential as biomarkers for distinguishing the BPD patients form the HCs.