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Gut Microbiome Characteristics Tied to Depressive Symptoms in New Studies

NEW YORK – New studies by researchers in the Netherlands, UK, and France have highlighted gut microbial community members and functional features that tend to coincide with depression in individuals from populations in the Netherlands and several other parts of the world.

"Our study suggests that the gut microbiome composition may play a key role in depression," co-corresponding authors Najaf Amin, an epidemiology and population health researcher affiliated with Erasmus MC University Medical Center Rotterdam and Oxford University, and Robert Kraaij, an internal medicine researcher at Erasmus Medical Center Rotterdam, and their colleagues wrote in Nature Communications on Tuesday.

For that study, the researchers relied on 16S ribosomal RNA sequencing to profile gut microbes in fecal samples from 1,054 individuals from the Rotterdam Study who were not taking anti-depressive medications, identifying more than a dozen gut microbial taxa with ties to self-reported, questionnaire-based depressive symptoms scores — results backed up by their subsequent analyses on samples from more than 1,500 Amsterdam HELIUS study participants.

In particular, the team saw altered gut levels of microbes from the Ruminococcaceae family, along with representatives from Eggerthella, Coprococcus, Hungatella, and other genera known for their roles in glutamate, butyrate, serotonin, and gamma amino butyric acid (GABA) synthesis, in individuals with relatively high depressive symptom scores.

Other microbial community representatives turned up at lower-than-usual levels in the guts of individuals with higher depression scores, the researchers reported, while species richness and other alpha diversity measurements tended to decline as depressive symptoms increased.

The team's subsequent Mendelian randomization analyses pointed to potential ties between major depressive disorder and Eggerthella, one of several depressive symptom-associated microbes implicated in major depression in the past. The study also pointed to an apparent association between depressive symptoms and body mass index that could not be attributed to antidepressant use in the untreated participants, while highlighting gut microbes that appear to coincide with both depression and atherosclerosis.

In another Nature Communications study, members of the same team broadened the search for ties between depressive symptoms and the gut microbiome by bringing in data for more than 3,200 individuals from half a dozen populations, including Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan urban individuals from the HELIUS cohort.

"Both the microbiome and depressive symptom levels vary substantially across ethnic groups," first and corresponding author Jos Bosch, a psychology and medical psychology researcher at the University of Amsterdam, and his colleagues wrote, noting that "any intervention for depression targeting the microbiome requires understanding of microbiome-depression associations across ethnicities."

The team's analyses of stool sample 16S sequences and self-reported depression scores from the diverse study participants revealed apparent relationships between depressive symptoms and gut microbes from the Ruminococcaceae, Christensenellaceae, and Lachnospiraceae families.

After adjusting for demographic factors such as age or sex, individuals' lifestyle or behavior, and known medical insights, the researchers found that depressive symptoms were linked to within-host diversity, dubbed alpha-diversity, as well as the beta-diversity measurements documenting differences from one individual to the next — patterns that held across the populations and ethnic backgrounds considered in the study.

The alpha-diversity relationship with depression appeared to largely reflect the impact of neuroticism, they noted. While the alpha-diversity association with depression did not hold after adjusting for that trait, the authors explained, the beta-diversity principal components "appeared impervious to adjustment by neuroticism, and these might thus identify the more depression-specific features of microbiota composition."

"The study findings identified potential targets for psychobiotic interventions that warrant further investigation," they suggested, "and may positively impact depression and well-being at an individual or population level."