Gut microbiome-wide association study of depressive symptoms

Abstract

Depression is one of the most poorly understood diseases due to its elusive pathogenesis. There is an urgency to identify molecular and biological mechanisms underlying depression and the gut microbiome is a novel area of interest. Here we investigate the relation of fecal microbiome diversity and composition with depressive symptoms in 1,054 participants from the Rotterdam Study cohort and validate these findings in the Amsterdam HELIUS cohort in 1,539 subjects. We identify association of thirteen microbial taxa, including genera Eggerthella, Subdoligranulum, Coprococcus, Sellimonas, Lachnoclostridium, Hungatella, Ruminococcaceae (UCG002, UCG003 and UCG005), LachnospiraceaeUCG001, Eubacterium ventriosum and Ruminococcusgauvreauiigroup, and family Ruminococcaceae with depressive symptoms. These bacteria are known to be involved in the synthesis of glutamate, butyrate, serotonin and gamma amino butyric acid (GABA), which are key neurotransmitters for depression. Our study suggests that the gut microbiome composition may play a key role in depression.

The gut microbiota and depressive symptoms across ethnic groups

“…After full adjustment (i.e., Model 3), 23 ASVs identifying at least 15 genera remained significantly associated with depression scores. These included a negative association with the abundant genus Coprococcus (designated GCA-900066575 in the Silva database), hereby confirming results from two independent population cohorts 13 and the Rotterdam study 24 . This genus harbors many butyrateproducing species and has been ascribed anti-inflammatory properties 43 , both of which have been (inversely) linked to depression.…”

“…The present results suggested that the custom of analysing bacteria at an aggregate level (e.g., genus, OTU) may be a potential cause of inconsistent findings in microbiome-depression studies 53 . It may thus also clarify some variance with the study of Radjabzadeh et al 24 , which used closed reference OTU clustering instead of ASVs. For example, we observed that ASVs identifying the genus Blautia, Bacteroides, or Oscillospira exhibited both significant positive and significant negative correlations with depressive symptom levels.…”

“…Overall, a majority of associations were within the phylum Firmicutes. Random forest analyses, using the Rotterdam Study as training cohort and HELIUS as the testing cohort 24 , replicated associations for several including Ruminococcaceae UCG005, Coprococcus, Lachnoclostridium, Eggerthella, Sellimonas, Roseburia, Bacteroides, Blautia, Veillonella, and Desulfovibrio, of which several were also retained in their adjusted analyses 24 .…”

“…Significantly, many of those taxa have also been linked to other domains of health 32,35,[37][38][39][40][41] , including health factors associated with increased depression risk (e.g., BMI). A prominent example was the genus Christensenellaceae (R-7 group), which likewise showed a negative association with depressive symptoms in the Rotterdam study cohort 24 . Further, and replicating prior research, Christensenellaceae abundances were additionally correlated with lower BMI and relatively depleted in the presence of diabetes and gastro-intestinal diseases 42 .…”

“…Finally, the present study aimed to assess if ethnic differences in gut microbiota may account for ethnic disparities in depression. A parallel study 24 provides a large-scale epidemiological investigation of the relation between fecal microbiota and depressive symptoms among subjects of European ancestry, cross-validating data from the Amsterdam HELIUS cohort and the Rotterdam Study cohort.…”