Aim: This study aims to develop new approaches to characterize brain networks to potentially contribute to a better understanding of mechanisms involved in depression. Method and subjects: We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed investigating functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were developed at a functional network level, using a false discovery rate method. Linear discriminant analysis was used to differentiate between the two groups. Results and discussion: Significant differences in functional connectivity (FC) between depressed patients vs. healthy controls was demonstrated, with brain regions including the lingual gyrus, cerebellum, midcingulate cortex and thalamus more prominent in healthy subjects as compared to depression where the orbitofrontal cortex emerged as a key node. Linear discriminant analysis demonstrated that full-connectivity matrices were the most precise in differentiating between depression vs. health subjects. Conclusion: The study provides supportive evidence for impaired functional connectivity networks in MDE patients.

Background: Increased intestinal permeability with heightened translocation of Gramnegative bacteria, also known as “leaky gut”, is associated with the pathophysiology of neuroimmune disorders, such as Major Depressive Disorder (MDD), Chronic Fatigue Syndrome (CSF) and (deficit) schizophrenia, as well as with general medical disorders, including irritable bowel syndrome. This review aims to summarize clinical biochemistry and molecular immunology tests that may aid in the recognition of leaky gut in clinical practice. Methods: We searched online libraries, including PubMed/MEDLINE, Google Scholar and Scopus, with the key words “diagnosis” or “biomarkers” and “leaky gut”, “bacterial translocation”, and “intestinal permeability” and focused on papers describing tests that may aid in the clinical recognition of leaky gut. Results: To evaluate tight junction barrier integrity, serum IgG/IgA/IgM responses to occludin and zonulin and IgA responses to actomyosin should be evaluated. The presence of cytotoxic bacterial products in serum can be evaluated using IgA/IgM responses to sonicated samples of common Gram-negative gut commensal bacteria and assays of serum lipopolysaccharides (LPSs) and other bacterial toxins, including cytolethal distenting toxin, subunit B. Major factors associated with increased gut permeability, including gut dysbiosis and yeast overgrowth, use of NSAIDs and alcohol, food hypersensitivities (IgE-mediated), food intolerances (IgG-mediated), small bacterial overgrowth (SIBO), systemic inflammation, psychosocial stressors, some infections (e.g., HIV) and dietary patterns, should be assessed. Stool samples can be used to assay gut dysbiosis, gut inflammation and decreased mucosal defenses using assays of fecal growth of bacteria, yeast and fungi and stool assays of calprotectin, secretory IgA, β-defensin, α- antitrypsin, lysozyme and lactoferrin. Blood and breath tests should be used to exclude common causes of increased gut permeability, namely, food hypersensitivities and intolerances, SIBO, lactose intolerance and fructose malabsorption. Discussion: Here, we propose strategies to recognize “leaky gut” in a clinical setting using the most adequate clinical chemistry and molecular immunology assays.