Gut Microbiome Composition Linked to Inflammatory Factors and Cognitive Functions in First-Episode, Drug-Naive Major Depressive Disorder Patients.

Penghong Liu,Lei Lei,Zhifen Liu,Chunxia Yang,Kerang Zhang,Aixia Zhang,Gaizhi Li,Mingxue Gao,Peiyi Wu,Yanyan Zhang,Ning Sun,Hongwei Tu

doi:10.3389/fnins.2021.800764

Abstract

ObjectiveThe microbiota–gut–brain axis, especially the inflammatory pathway, may play a critical role in the pathogenesis of cognitive impairment in major depressive disorder (MDD). However, studies on the microbiota-inflammatory-cognitive function axis in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and explore the correlation between gut microbiota and inflammatory factors, cognitive function in MDD patients.MethodStudy participants included 66 first-episode, drug naïve MDD patients as well as 43 healthy subjects (HCs). The composition of fecal microbiota was evaluated using16S rRNA sequencing and bioinformatics analysis. The cytokines such as hs-CRP, IL-1β, IL-6, IL-10, and TNF-α in peripheral blood were detected via enzyme linked immunosorbent assay (ELISA); assessment of cognitive functions was performed using the Color Trail Test (CTT), The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (SCWT).ResultsWe found that compared with HCs, MDD patients had cognitive impairments and showed different α-diversity and β-diversity of gut microbiota composition. LDA effect size (LEfSe) analysis found MDD have higher Deinococcaceae and lower Bacteroidaceae, Turicibacteraceae, Clostridiaceae and Barnesiellaceae at family level. Deinococcus and Odoribacter was higher in the MDD group, however, Bacteroides, Alistipes, Turicibacter, Clostridium, Roseburia, and Enterobacter were lower at genus level. Furthermore, In MDD patients, the Bacteroidaceae and Bacteroides were both positively correlated with hsCRP, CCT1, CCT2. Alistipes was positively correlated with IL-6, Word time, Color time, Word-Color time, Color-Word time and negatively correlated with Delayed Memory, Total score and Standardized score. Turicibacteraceae and Turicibacter were both negatively correlated with IL-1β and IL-6.ConclusionThe present findings confirm that the gut microbiota in MDD patients have altered gut microbes that are closely associated with inflammatory factors and cognitive function in MDD patients.

Highlights

Gut microbiota functions as a vital actor in the bidirectional communication between the digestive system and the central nervous system (CNS), called the brain–gut–microbiota axis (Rhee et al, 2009)
A study conducted by Naseribafrouei et al (2014) analyzed the state of gut microbiota in individuals with major depressive disorder (MDD) and healthy controls (HCs), and reported that when Bacteroidales, Oscillibacter, and Alistipes were present in higher levels, the Lachnospiraceae were linked with depressive symptoms
We uncovered no significant discrepancies in the age, gender, or BMI of the MDD patients and HCs (P > 0.05)

Summary

Introduction

Gut microbiota functions as a vital actor in the bidirectional communication between the digestive system and the central nervous system (CNS), called the brain–gut–microbiota axis (Rhee et al, 2009). A study conducted by Naseribafrouei et al (2014) analyzed the state of gut microbiota in individuals with MDD and healthy controls (HCs), and reported that when Bacteroidales, Oscillibacter, and Alistipes were present in higher levels, the Lachnospiraceae were linked with depressive symptoms. Other researchers studied the gut microbiota present in active-MDD (A-MDD) subjects, responding-MDD (R-MDD) subjects, and HCs (Jiang et al, 2015). They discovered that MDD patients had increased Proteobacteria, Bacteroidetes, and Actinobacteria, as well as decreased Faecalibacterium. Faecalibacterium was negatively associated with depressive symptom severity (Jiang et al, 2015). Zheng et al (2016) found higher levels of Actinobacteria and Bacteroidetes and lower levels of Firmicutes in MDD patients; they found that transferring MDD feces into germ-free (GF) mice resulted in depressive phenotypes in recipient mice

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