‘Novel findings’
In the fully adjusted analysis, metabolic signatures of MDD were found to consist of 124 metabolites that spanned energy and lipid metabolism pathways.
The investigators noted that these “novel findings” included 49 metabolites encompassing those involved in the tricarboxylic acid cycle – citrate and pyruvate.
The findings revealed that fatty acids and intermediate and VLDL changed in association with the disease process. On the other hand, HDL and the metabolites in the tricarboxylic acid cycle did not.
“We observed that the genera Sellimonas, Eggerthella, Hungatella, and Lachnoclostridium were more abundant, while genera Ruminococcaceae ... Coprococcus, Lachnospiraceae ... Eubacterium ventriosum, Subdoligranulum, and family Ruminococcaceae were depleted in the guts of individuals with more symptoms of depression,” said Dr. Amin. “Of these, genus Eggerthella showed statistical evidence of being involved in the causal pathway.”
These microbes are involved in the synthesis of important neurotransmitters, such as gamma aminobutyric acid, butyrate, glutamate, and serotonin, she noted.
Butyrate produced by the gut can cross the blood-brain barrier, enter the brain, and affect transcriptional and translational activity or be used by the cells for generating energy, she added. “So basically, butyrate can influence depression through several routes – i.e., via immune regulation, genomic transcript/translation, and/or affecting energy metabolism.”
No causality
Commenting on the study, Emeran Mayer, MD, distinguished research professor of medicine, G. Oppenheimer Center for Neurobiology of Stress and Resilience and UCLA Brain Gut Microbiome Center, called it the “largest, most comprehensive and best validated association study to date providing further evidence for an association between gut microbial taxa, previously identified in patients with MDD, blood metabolites (generated by host and by microbes) and questionnaire data.”
However, “despite its strengths, the study does not allow [us] to identify a causal role of the microbiome alterations in the observed microbial and metabolic changes (fatty acids, Krebs cycle components),” cautioned Dr. Mayer, who was not involved with the study.
Moreover, “causality of gut microbial changes on the behavioral phenotype of depression cannot been inferred,” he concluded.
Metabolomics data were provided by the Alzheimer’s Disease Metabolomics Consortium. The study was funded wholly or in part by grants from the National Institute on Aging and Foundation for the National Institutes of Health. It was further supported by a grant from ZonMW Memorabel. Dr. Amin reports no relevant financial relationships. The other authors’ disclosures are listed oin the original article. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
A version of this article originally appeared on Medscape.com.