Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities

AbstractAlthough alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.

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Analysis of gut microbiota and intestinal integrity markers of inpatients with major depressive disorder

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2020.110076 ◽

2021 ◽

Vol 106 ◽

pp. 110076 ◽

Cited By ~ 1

Author(s):

Paweł Liśkiewicz ◽

Mariusz Kaczmarczyk ◽

Błażej Misiak ◽

Michał Wroński ◽

Agata Bąba-Kubiś ◽

...

Keyword(s):

Major Depressive Disorder ◽

Gut Microbiota ◽

Depressive Disorder ◽

Major Depressive ◽

Intestinal Integrity

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Associations between gut microbiota and Alzheimer’s disease, major depressive disorder, and schizophrenia

Journal of Neuroinflammation ◽

10.1186/s12974-020-01961-8 ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Zhenhuang Zhuang ◽

Ruotong Yang ◽

Wenxiu Wang ◽

Lu Qi ◽

Tao Huang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Major Depressive Disorder ◽

Gut Microbiota ◽

Depressive Disorder ◽

Lower Risk ◽

Neuropsychiatric Disorders ◽

Microbiota Composition ◽

Major Depressive ◽

Gut Microbiota Composition

Abstract Background Growing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions. However, whether such associations reflect causality remains unknown. We aimed to reveal the causal relationships among gut microbiota, metabolites, and neuropsychiatric disorders including Alzheimer’s disease (AD), major depressive disorder (MDD), and schizophrenia (SCZ). Methods A two-sample bi-directional Mendelian randomization analysis was performed by using genetic variants from genome-wide association studies as instrumental variables for gut microbiota, metabolites, AD, MDD, and SCZ, respectively. Results We found suggestive associations of host-genetic-driven increase in Blautia (OR, 0.88; 95%CI, 0.79–0.99; P = 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92–1.00; P = 0.034), a downstream product of Blautia-dependent arginine metabolism, with a lower risk of AD. Genetically increased Enterobacteriaceae family and Enterobacteriales order were potentially associated with a higher risk of SCZ (1.09; 1.00–1.18; P = 0.048), while Gammaproteobacteria class (0.90; 0.83–0.98; P = 0.011) was related to a lower risk for SCZ. Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00–1.15; P = 0.047). Furthermore, genetically increased Bacilli class was related to a higher risk of MDD (1.07; 1.02–1.12; P = 0.010). In the other direction, neuropsychiatric disorders altered gut microbiota composition. Conclusions These data for the first time provide evidence of potential causal links between gut microbiome and AD, MDD, and SCZ. GABA and serotonin may play an important role in gut microbiota-host crosstalk in AD and SCZ, respectively. Further investigations in understanding the underlying mechanisms of associations between gut microbiota and AD, MDD, and SCZ are required.

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Gut Microbiota Metabolites in Major Depressive Disorder. Deep Insights into Their Pathophysiological Role and Potential Translational Applications

Metabolites ◽

10.3390/metabo12010050 ◽

2022 ◽

Vol 12 (1) ◽

pp. 50

Author(s):

Miguel A. Ortega ◽

Miguel Angel Alvarez-Mon ◽

Cielo García-Montero ◽

Oscar Fraile-Martinez ◽

Luis G. Guijarro ◽

...

Keyword(s):

Major Depressive Disorder ◽

Gut Microbiota ◽

Depressive Disorder ◽

Disease Status ◽

Short Chain Fatty Acids ◽

Human Organism ◽

Microbial Metabolites ◽

Clinical Value ◽

Major Depressive ◽

Health And Disease

The gut microbiota is a complex and dynamic ecosystem essential for the proper functioning of the organism, affecting the health and disease status of the individuals. There is continuous and bidirectional communication between gut microbiota and the host, conforming to a unique entity known as “holobiont”. Among these crosstalk mechanisms, the gut microbiota synthesizes a broad spectrum of bioactive compounds or metabolites which exert pleiotropic effects on the human organism. Many of these microbial metabolites can cross the blood–brain barrier (BBB) or have significant effects on the brain, playing a key role in the so-called microbiota-gut-brain axis. An altered Microbiota-Gut-Brain (MGB) axis is a major characteristic of many neuropsychiatric disorders, including major depressive disorder (MDD). Significative differences between gut eubiosis and dysbiosis in mental disorders like MDD with their different metabolite composition and concentrations are being discussed. In the present review, the main microbial metabolites (short-chain fatty acids -SCFAs-, bile acids, amino acids, tryptophan -trp- derivatives, and more), their signaling pathways and functions will be summarized to explain part of MDD pathophysiology. Conclusions from promising translational approaches related to microbial metabolome will be addressed in more depth to discuss their possible clinical value in the management of MDD patients.

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Major depressive disorder: how to evaluate and manage patients with psychiatric and medical comorbidities

Mental Disorders in Primary Care ◽

10.1093/med/9780198746638.003.0019 ◽

2017 ◽

Author(s):

Sheng-Min Wang ◽

Chi-Un Pae

Keyword(s):

Primary Care ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Health Condition ◽

High Rate ◽

Health Concern ◽

Comorbid Conditions ◽

Major Depressive ◽

Medical Comorbidities ◽

Care Models

Major depressive disorder (MDD) is a highly prevalent, chronic, and recurring mental health condition. A substantially high rate of psychiatric and medical comorbidities occurs in individuals with MDD. Furthermore, MDD and these related comorbidities often exhibit bidirectional and reciprocal relationships, where psychiatric and medical comorbidities worsen the prognosis of MDD, and vice-versa. However, the significant symptomatic overlap between MDD and other chronic psychiatric and medical comorbid conditions imposes significant challenges for the assessment and management of these patients in primary care settings. Thus, the influence of psychiatric and medical comorbidities in the treatment of MDD has increasingly become an issue of major public health concern. Collaborative care models hold promise as an effective strategy for the management MDD and comorbid conditions in primary care. This chapter comprehensively reviews evidence pertaining to the evaluation and treatment of MDD and comorbid chronic health conditions in primary care.

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Major Depressive Disorder and gut microbiota – Association not causation. A scoping review

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2020.110111 ◽

2021 ◽

Vol 106 ◽

pp. 110111 ◽

Cited By ~ 1

Author(s):

Igor Łoniewski ◽

Agata Misera ◽

Karolina Skonieczna-Żydecka ◽

Mariusz Kaczmarczyk ◽

Karolina Kaźmierczak-Siedlecka ◽

...

Keyword(s):

Major Depressive Disorder ◽

Gut Microbiota ◽

Depressive Disorder ◽

Scoping Review ◽

Major Depressive

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Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in major depressive disorder patients

Psychological Medicine ◽

10.1017/s0033291719003027 ◽

2019 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Wen-tao Lai ◽

Wen-feng Deng ◽

Shu-xian Xu ◽

Jie Zhao ◽

Dan Xu ◽

...

Keyword(s):

Major Depressive Disorder ◽

Gut Microbiota ◽

Depressive Disorder ◽

Characteristic Curve ◽

Critical Role ◽

Metagenomic Sequencing ◽

Major Depressive ◽

Shotgun Metagenomics ◽

Shotgun Metagenomic Sequencing ◽

Tryptophan Pathway

Abstract Background The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients. Methods We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD. Results The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890. Conclusions The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.

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Exploring the Role of Gut Microbiota in Major Depressive Disorder and in Treatment Resistance to Antidepressants

Biomedicines ◽

10.3390/biomedicines8090311 ◽

2020 ◽

Vol 8 (9) ◽

pp. 311

Author(s):

Andrea Fontana ◽

Mirko Manchia ◽

Concetta Panebianco ◽

Pasquale Paribello ◽

Carlo Arzedi ◽

...

Keyword(s):

Major Depressive Disorder ◽

Gut Microbiota ◽

Depressive Disorder ◽

Treatment Resistance ◽

Major Depressive ◽

Bacterial Populations ◽

The Family ◽

Stool Samples ◽

Penalized Logistic Regression

Major depressive disorder (MDD) is a common severe psychiatric illness, exhibiting sub-optimal response to existing pharmacological treatments. Although its etiopathogenesis is still not completely understood, recent findings suggest that an altered composition of the gut microbiota might play a role. Here we aimed to explore potential differences in the composition of the gut microbiota between patients with MDD and healthy controls (HC) and to identify possible signatures of treatment response by analyzing two groups of MDD patients characterized as treatment-resistant (TR) or responders (R) to antidepressants. Stool samples were collected from 34 MDD patients (8 TR, 19 R and 7 untreated) and 20 HC. Microbiota was characterized using the 16S metagenomic approach. A penalized logistic regression analysis algorithm was applied to identify bacterial populations that best discriminate the diagnostic groups. Statistically significant differences were identified for the families of Paenibacillaceae and Flavobacteriaceaea, for the genus Fenollaria, and the species Flintibacter butyricus, Christensenella timonensis, and Eisenbergiella massiliensis among others. The phyla Proteobacteria, Tenericutes and the family Peptostreptococcaceae were more abundant in TR, whereas the phylum Actinobacteria was enriched in R patients. Moreover, a number of bacteria only characterized the microbiota of TR patients, and many others were only detected in R. Our results confirm that dysbiosis is a hallmark of MDD and suggest that microbiota of TR patients significantly differs from responders to antidepressants. This finding further supports the relevance of an altered composition of the gut microbiota in the etiopathogenesis of MDD, suggesting a role in response to antidepressants.

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