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Depression-Related Gut Microbiome, Metabolite Changes Lead to Potential Biomarker Set

NEW YORK – A team of researchers from China and the US has identified microbial community and metabolite shifts in individuals with major depressive disorder (MDD), along with a set of half a dozen gut microbe and metabolite markers characterizing their disease.

"Our findings lay the foundation for understanding the roles of the overall gut ecosystem in MDD pathogenesis and may facilitate developing objective MDD diagnostic methods," co-corresponding authors Peng Xie, Gang Wang, and Shaohua Hu and their team wrote.

As they reported in Science Advances on Wednesday, the researchers, from Capital Medical University, First Affiliated Hospital of Chongqing Medical University, and elsewhere, used a combination of whole-genome shotgun metagenomic sequencing and gas chromatography mass spectrometry-based metabolomics to assess more than 300 fecal samples from 156 individuals with MDD and 155 healthy, depression-free control individuals.

The team's search uncovered changes in gut bacteria and the bacteria-infecting bacteriophage virus community, as well as corresponding microbial metabolite changes. Follow-up analyses suggested that a combination of gut microbial membership and metabolite features can help flag individuals with depression and distinguish them from unaffected controls.

"Together, using multi-omics data, we have presented evidence that MDD was characterized by the disturbances of gut bacteriophages, bacteria, and fecal metabolites, which represented the overall disturbances of MDD gut ecology," the authors reported, noting that "disturbances of microbial amino acid metabolism was a hallmark in the gut ecosystem of MDD."

For the discovery stage of the study, the researchers profiled 236 fecal samples from individuals being treated for MDD at a psychiatric center in China and from unaffected control individuals, uncovering nearly four dozen bacterial species with distinct representation in gut microbial communities of MDD patients.

"Patients with MDD were mainly characterized by increased abundance of the genus Bacteroides and decreased abundance of the genera Blautia and Eubacterium," they wrote, noting that "multilevel omics alterations generated a characteristic MDD co-expression network."

The MDD cases were also marked by altered levels of three bacteria-infecting bacteriophage viruses and 50 fecal metabolites, the team found, including metabolites stemming from changes to phenylalanine, tryptophan, and gamma-aminobutyrate amino acid metabolism.

After confirming the microbial and metabolite patterns in a validation set of 75 fecal samples from cases and controls, the investigators dug into the data to uncover a panel of related markers that appeared to distinguish between MDD cases and controls with around 87 percent specificity and at least 95 percent sensitivity in the discovery and validation cohorts they considered.

Moreover, the team saw hints that the presence or absence of four bacterial species, along with fecal levels of two metabolites, may help identify individuals with more severe forms of MDD.

"Together," the authors concluded, "these findings provide new directions to uncover pathogenesis and develop novel diagnostic strategies for MDD."