Differences in gut microbiota correlate with symptoms and regional brain volumes in patients with late-life depression

Vasupanrajit

et al. 2023

Preprint

The first publication demonstrating that major depressive disorder (MDD) is associated with alterations in the gut microbiota appeared in 2008 (Maes et al., 2008). The purpose of the present study is to delineate a) the microbiome signature of the phenome of depression, including suicidal behaviours and cognitive deficits; the effects of adverse childhood experiences (ACE) and recurrence of illness index (ROI) on the microbiome; and the microbiome signature of lowered high-density lipoprotein cholesterol (HDLc). We determined isometric log-ratio abundances or prevalences of gut microbiome phyla, genera, and species by analysing stool samples from 37 healthy Thai controls and 32 MDD patients using 16S rDNA sequencing. Six microbiome taxa accounted for 36% of the variance in the depression phenome, namely Hungatella and Fusicatenibacter (positive associations) and Butyricicoccus, Clostridium, Parabacteroides merdae, and Desulfovibrio piger (inverse association). This profile (labeled enterotype 1) indicates compositional dysbiosis, is strongly predicted by ACE and ROI, and is linked to suicidal behaviours. A second enterotype was developed that predicted a decrease in HDLc and an increase in the atherogenic index of plasma (Bifidobacterium, P. merdae, and Romboutsia were positively associated, while Proteobacteria and Clostridium sensu stricto were negatively associated). Together, enterotypes 1 and 2 explained 40.4% of the variance in the depression phenome, and enterotype 1 in conjunction with HDLc explained 39.9% of the variance in current suicidal behaviours. In conclusion, the microimmuneoxysome is a potential new drug target for the treatment of severe depression and suicidal behaviours, and possibly for the prevention of future episodes.

Section: Discussioncontrasting

confidence: 75%

Adverse childhood trauma and reoccurrence of illness impact the gut microbiome, which affects suicidal behaviors and the phenome of major depression: towards enterotypic-phenotypes

Vasupanrajit

et al. 2023

Preprint

“…Although this LEfSe analysis discovered numerous discriminative taxa at an LDA threshold of > 3, there were no parallels between our findings and those of Ling et al Moreover, whilst we discovered that Gemmiger and Desulfovibrio were abundant in controls, Ling et al [81] discovered the opposite. There are no similarities between our results (obtained in younger MDD patients and controls) and those of patients with late-life depression [82], despite the fact that the latter LEfSe analysis found many significant abundances of bacterial taxa at the genus level in controls as opposed to patients with late-life depression.…”

Section: Abundance Of Gut Microbiome Taxa In Mddcontrasting

confidence: 74%

Exploration of the Gut Microbiome in Thai Patients with Major Depressive Disorder Shows a Specific Bacterial Profile with Depletion of the Ruminococcus Genus as a Putative Biomarker

et al. 2023

Cells

Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota–gut–brain axis, as evidenced by elevated serum IgM/IgA to lipopolysaccharides (LPS) of Gram-negative bacteria, such as Morganella morganii and Klebsiella Pneumoniae. The latter aberrations, which point to increased gut permeability (leaky gut), are linked to activated neuro-immune and oxidative pathways in MDD. To delineate the profile and composition of the gut microbiome in Thai patients with MDD, we examined fecal samples of 32 MDD patients and 37 controls using 16S rDNA sequencing, analyzed α- (Chao1 and Shannon indices) and β-diversity (Bray–Curtis dissimilarity), and conducted linear discriminant analysis (LDA) effect size (LEfSe) analysis. Neither α- nor β-diversity differed significantly between MDD and controls. Rhodospirillaceae, Hungatella, Clostridium bolteae, Hungatella hathewayi, and Clostridium propionicum were significantly enriched in MDD, while Gracillibacteraceae family, Lutispora, and Ruminococcus genus, Ruminococcus callidus, Desulfovibrio piger, Coprococcus comes, and Gemmiger were enriched in controls. Contradictory results have been reported for all these taxa, with the exception of Ruminococcus, which is depleted in six different MDD studies (one study showed increased abundance), many medical disorders that show comorbidities with MDD, and animal MDD models. Our results may suggest a specific profile of compositional gut dysbiosis in Thai MDD patients, with increases in some pathobionts and depletion of some beneficial microbiota. The results suggest that depletion of Ruminococcus may be a more universal biomarker of MDD that may contribute to increased enteral LPS load, LPS translocation, and gut–brain axis abnormalities.

“…Although this LefSe analysis discovered numerous discriminative taxa at an LDA threshold of > 3, there were no parallels between our findings and those of Ling et al Moreover, whilst we discovered that Gemmiger and Desulfovibrio were abundant in controls, Ling et al [82] discovered the opposite. There are no similarities between our results (obtained in younger MDD patients and controls) and those of patients with late-life depression [83], despite the fact that the latter LEfSe analysis found many significant abundances of bacterial taxa at the genus level in controls as opposed to patients with late-life depression.…”

Section: Abundance Of Gut Microbiome Taxa In Mddcontrasting

confidence: 74%

Exploration of the gut microbiome in Thai patients with major depressive disorder uncovered a specific bacterial profile with depletion of theRuminococcusgenus as a putative biomarker

Vasupanrajit

et al. 2022

Preprint

Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota-gut-brain axis, as evidenced by elevated serum IgM/IgA to lipopolysaccharides (LPS) of Gram-negative bacteria, such as Morganella morganii and Klebsiella Pneumoniae. The latter aberrations, which point to increased gut permeability (leaky gut), are linked to activated neuro-immune and oxidative pathways in MDD. To delineate the profile and composition of the gut microbiome in Thai patients with MDD, we examined fecal samples of 32 MDD patients and 37 controls using 16S rDNA sequencing and analyzed α- (Chao and Shannon indices) and β-diversity (Bray-Curtis dissimilarity) and conducted Linear discriminant analysis (LDA) Effect Size (LEfSe) analysis. Neither α- nor β-diversity differed significantly between MDD and controls. Rhodospirillaceae, Hungatella, Clostridium bolteae, Hungatella hathewayi, and Clostridium propionicum were significantly enriched in MDD, while Gracillibacteraceae family, Lutispora, and Ruminococcus genus, Ruminococcus callidus, Desulfovibrio piger, Coprococcus comes, and Gemmiger, were enriched in controls. Contradictory results have been reported for all these taxa, with the exception of Ruminococcus which is depleted in 6 different MDD studies (one study showed increased abundance), many medical disorders that show comorbidities with MDD, and animal MDD models. Our results may suggest a specific profile of compositional gut dysbiosis in Thai MDD patients with increases in some pathobionts and depletion of some beneficial microbiota. The results suggest that depletion of Ruminococcus may be a more universal biomarker of MDD that maybe contributes to increased enteral LPS load, LPS translocation, and gut-brain axis abnormalities.