Relationships of oxidative stress, inflammation and gut microbiota with cognitive impairment in first-episode major depressive disorders: a pilot study in China
The research showed that the GM and their predicted metabolic pathways in patients with MDD were closely related to cognitive function and peripheral blood indicators, and that differences in these factors may manifest as oxidative stress and inflammation.
Abstract
Objective Cognitive impairment runs through the entire course of major depressive disorder (MDD). However, the relationships between cognitive impairment and the gut microbiota (GM) and their predicted metabolic pathways as well as peripheral blood indicators remains unclear. We aimed to explore these relationships. Method Patients (n = 61) and healthy controls (HCs, n = 84) were enrolled. Our analyses were performed using data from the Hamilton Depression Scale, cognitive function (MATRICS™ Consensus Cognitive Battery [MCCB]), the GM and their predicted metabolic pathways, and peripheral blood indicators, including homocysteine (Hcy), superoxide dismutase (SOD), and C-reactive protein (CRP). Results In comparison with HCs, patients with MDD exhibited significant cognitive impairment, elevated SOD levels, enrichment of specific GM, and upregulation of microbial predicted metabolic pathways involving L-alanine, pyruvate, and salicortin. In patients with MDD, the salicortin biosynthesis pathway and pathways related to L-alanine metabolism were negatively correlated with the levels of Hcy and CRP, respectively, while the superpathway of de novo pyrimidine deoxyribonucleotide biosynthesis was positively correlated with the SOD levels. The abundance of Blautia_caecimuris and Dysosmobacter_sp._NSJ-60 was positively correlated with the scores for processing speed and attention/vigilance domain, while the abundance of Enterocloster_aldenensis was negatively correlated with the score for working memory. Moreover, the 6-gingerol analog biosynthesis pathway was negatively correlated with the score for processing speed. Conclusion Our research showed that the GM and their predicted metabolic pathways in patients with MDD were closely related to cognitive function and peripheral blood indicators, and that differences in these factors may manifest as oxidative stress and inflammation.
Current state-of-the-art neuroimmune, metabolic, and oxidative stress (NIMETOX) knowledge that has been developed in clinical major depressive disorder (MDD) research over the past three decades is explored in this review. Between 1990 and 2000, the acute phase of severe MDD was characterized by the activation of T helper (Th)1 cells and M1 macrophages, leading to immune dysregulation that affects nutritional immunity and alters protein, tryptophan, iron, and lipid metabolism. The latter comprises lower high-density lipoprotein cholesterol, reverse cholesterol transport (RCT), ω3 polyunsaturated fatty acids, heightened lipid peroxidation and atherogenicity. Additionally, immune alterations regulate stress-responsive systems and modify the biological basis of depressive symptoms through neurotoxic effects and reduced neuroprotection. The incremental information acquired from 2000 to 2026 revealed that the acute phase of severe MDD is characterized by immune sensitization, imbalances between the compensatory immunoregulatory system (CIRS) and the immune-inflammatory response system (IRS) and that there are multiple interactions between increased atherogenicity, metabolic syndrome, oxidative stress, and lower antioxidant activity and RCT. Additionally, the NIMETOX pathway may be fuelled by increased expression of TLR4 and NF-κB intracellular signaling driven by increased lipopolysaccharides, lipids, and oxidatively modified epitopes. This paper presents evidence that peripheral NIMETOX pathways may lead to neuroinflammation, microglial activation, and neuronal damage and that increased lipid load impairs these central pathways. This paper assesses the field’s future advancements by conducting a comprehensive examination of the reviewed knowledge base, deep phenotyping, panomics methodologies, and machine learning techniques, including the nomothetic precision approach.
Michael Maes, A. Almulla, D. Stoyanov et al.· Cellular & Molecular Immunol...· 0 citations
OBJECTIVES
The underlying mechanism of major depressive disorder (MDD) with eating disorder (ED) remains unclear. We aim to clarify the characteristic changes of THs and brain neurometabolic alterations in ED, and to explore their relationships.
METHODS
The study included 28 individuals with MDD and ED, 81 individuals with MDD without ED, and 37 age-matched healthy controls (HCs). Serum TH levels were assessed, and 1H proton magnetic spectroscopy was utilized to determine the N-acetylaspartic acid to creatine (NAA/Cr) and choline-containing compounds to creatine ratios in the prefrontal cortex, anterior cingulate cortex, and thalamus. Subsequently, differential analysis, receiver operating characteristic (ROC) analysis, and correlation analysis were performed to explore their characteristics and interrelationships.
RESULTS
In both MDD with ED and MDD without ED cohorts, free tri-iodothyronine (FT3) levels were significantly lower compared to HCs, whereas free thyroxine (FT4) and total thyroxine (TT4) levels were elevated. Significantly lower NAA/Cr ratios were observed in the right thalamus and higher NAA/Cr ratios in the left cerebellum in both MDD with ED and MDD without ED compared to HCs. Neurometabolic factors and THs levels achieved an ROC curve area of 0.830 in differentiating MDD with ED from MDD without ED. In addition, serum FT3 and TT4 levels showed a positive correlation with NAA/Cr in the eft cerebellum in cases of MDD with ED.
CONCLUSIONS
Our findings reveal concurrent thyroid hormone irregularities and neurometabolic changes in the thalamic-cerebellum circuitry in MDD with ED, providing preliminary insights into the neurobiology of abnormal eating behaviors in depression. Given the cross-sectional design, these results are exploratory and require validation. Level of evidence Level IV, cross-sectional study.
Yangyu Wu, Qilin Zhong, Jianzhao Zhang et al.· Eating and Weight Disorders· 0 citations
Background: Major depressive disorder (MDD) is heterogeneous, and low-grade systemic inflammation may contribute to illness in a clinically relevant subgroup.
Methods: This narrative review examined human studies published between January 2010 and June 2026, prioritizing systematic reviews, meta-analyses, cohort studies, central biomarker research, and randomized trials.
Results: Approximately one-quarter of patients with depression have CRP levels above 3 mg/L, supporting an inflammatory phenotype rather than a universal inflammatory model. Immune signals may affect brain function through blood–brain barrier, neural, neurovascular, and metabolic pathways, influencing neurotransmission, stress regulation, oxidative balance, and neuroplasticity. CRP is the most accessible clinical marker, but no biomarker reliably identifies inflammatory depression. Anti-inflammatory treatments show inconsistent benefits, with the strongest signals observed in biomarker-selected patients.
Conclusion: Inflammation contributes to MDD in some patients, but single-marker diagnosis and routine anti-inflammatory treatment are not currently justified. Biomarker-stratified trials are needed to develop precision therapies.
Emilia Włoszek, Bartosz Mikołajek, Anita Godlewska et al.· African Journal of Biomedica...· 0 citations
Systemic inflammation is increasingly linked to Major Depressive Disorder (MDD), and its expression may vary across populations. This study evaluates serum high sensitive C-reactive protein (hs-CRP) and Interleukin-1β (IL-1β) levels in MDD patients (n-40) and healthy controls (n=40) to understand the biological basis of depression within the unique ethnic and environmental context of Sikkim. Females were the majority in both MDD (67.5%) and control (70%) groups. Most participants had a normal BMI (MDD: 62.5%, Control: 67.5%), with few cases of obesity or underweight. Nepali ethnicity was predominant in both MDD: 80% and,Control: 77.5% followed by Bhutias and others however statistically insignificant. hs-CRP differed significantly between MDD (3335.7 pg/L) and controls (3164.7 pg/L) P< 0.05, though it did not vary by depression severity. hs-CRP showed fair diagnostic ability (AUC = 0.746, 95% CI: 0.638–0.854, P< 0.01; sensitivity 65%, specificity 77.5%), whereas IL-1β demonstrated poor performance. hs–CRP shows potential as an adjunct inflammatory marker in assessing depression. Future studies should explore composite biomarker approach combined with clinical tools to enhance diagnostic and treatment strategies.
Aiusha Mawlong, Rinchen D. Bhutia, S. S. Bhandari et al.· Indian Journal of Biochemist...· 0 citations
Background Alterations in the gut microbiota have been associated with a variety of psychiatric disorders, including major depressive disorder (MDD). However, the relationship between MDD and gut microbial communities remains incompletely understood. Most previous studies have primarily focused on gut bacteria, with relatively limited attention to other microbial components. Methods In this study, we analyzed gut microbial profiles from 36 patients with MDD and 36 healthy controls using metagenomic sequencing data. The MaAsLin2 algorithm was applied to identify potential microbial biomarkers associated with MDD. Results A total of 6 bacterial biomarkers and 7 viral biomarkers were identified. The models based on these features demonstrated strong predictive performance, with area under the curve (AUC) values of 0.891 for bacteria and 0.878 for viruses. Notably, the combined bacterial-viral model achieved an AUC of 0.946. These findings were further evaluated through external testing in two unrelated research cohorts. In the Shanxi cohort, the AUC values were 0.825 (bacteria), 0.803 (viruses), and 0.972 (combined model). In the Wuhan cohort, the AUC values were 0.683 (bacteria), 0.693 (viruses), and 0.784 (combined model). Conclusion In summary, our results highlight the potential of gut bacterial and viral biomarkers as candidate biomarkers and potential auxiliary tools for MDD assessment and suggest that integrating multi-domain microbial features may improve prediction accuracy.
Xuan Wang, Wei Chen, Hanlin Zhang et al.· Frontiers in Cellular and In...· 0 citations
Although PA level was not significantly associated with overall gut microbial diversity in college students with SD, it was closely associated with the differential distribution of specific functional genera, closely associated with the differential distribution of specific functional genera.
Meihua Su, Jiahui Jin, Fengxun Lin et al.· Frontiers in Microbiology· 0 citations