The neuroactive potential of the human gut microbiota in quality of life and depression.
Valles-Colomer M, Falony G, Darzi Y, Tigchelaar EF, Wang J, Tito RY, Schiweck C, Kurilshikov A, Joossens M, Wijmenga C, Claes S, Van Oudenhove L, Zhernakova A, Vieira-Silva S, Raes J
Nat Microbiol. Feb 2019. doi: 10.1038/s41564-018-0337-x
COMMENT: This work is focused to the neuroactive potential of the human gut microbiome and is centered in studying how microbiome features correlate with host quality of life and depression. The findings of this work add new support for the importance of the brain-gut microbiome axis demonstrating in this case the microbial neuroactive impact in depression. The microbiota compositional covariation with quality of life (QoL) and depression was analyzed in 1,054 individuals participating in the Belgian Flemish Gut Flora Project (FGFP).
In this study, we first assess gut microbiota compositional covariation with quality of life (QoL) indicators and general practitioner reported depression in the Belgian Flemish Gut Flora Project (FGFP) population cohort (n = 1,054). We validate results both in the Dutch LifeLines DEEP (LLD) cohort with associated QoL and self-reported depression metadata (n = 1,063) and in previously published case–control studies on depression
Butyrate-producing Faecalibacterium and Coprococcus bacteria were consistently associated with higher quality of life indicators. Together with Dialister, Coprococcus spp. were also depleted in depression, even after correcting for the confounding effects of antidepressants.
While Coprococcus and Dialister were both found to be positively associated with QoL and depleted in treatment-free depression, others, including Butyricicoccus, were found to be linked to antidepressant treatment.
To study the gut microbiota–brain interaction beyond taxonomic associations, we developed a module-based analytical framework enabling targeted profiling and interpretation of metagenomic data in the context of microbiota–gut–brain communication. This framework describes the microbial pathways that metabolize molecules that have the potential to interact with the human nervous system (neuroactive compounds). From literature review, we curated and annotated 56 gut–brain modules (GBMs), each corresponding to a single neuroactive compound production or degradation process.
Gut–brain module analysis of faecal metagenomes identified the microbial synthesis potential of the dopamine metabolite 3,4-dihydroxyphenylacetic acid as correlating positively with mental quality of life and indicated a potential role of microbial γ-aminobutyric acid production in depression. Our results provide population-scale evidence for microbiome links to mental health, while emphasizing confounder importance.
We showed that several microbial pathways, including GABA and tryptophan metabolism, are enriched in human gut-associated microorganisms, indicating a potential role in host–microbe symbiosis. In addition, three GBMs correlated with QoL, including synthesis of the dopamine metabolite DOPAC.