Metabolic and Microbiota Measures as Peripheral Biomarkers in Major Depressive Disorder

Abstract

Advances in understanding the role of the microbiome in physical and mental health are at the forefront of medical research and hold potential to have a direct impact on precision medicine approaches. In the past 7 years, we have studied the role of microbiota-brain communication on behavior in mouse models using germ-free mice, mice exposed to antibiotics, and healthy specific pathogen free mice. Through our work and that of others, we have seen an amazing increase in our knowledge of how bacteria signal to the brain and the implications this has for psychiatry. Gut microbiota composition and function are influenced both by genetics, age, sex, diet, life experiences, and many other factors of psychiatric and bodily disorders and thus may act as potential biomarkers of the gut-brain axis that could be used in psychiatry and co-morbid conditions. There is a particular need in major depressive disorder and other mental illness to identify biomarkers that can stratify patients into more homogeneous groups to provide better treatment and for development of new therapeutic approaches. Peripheral outcome measures of host-microbe bidirectional communication have significant translational value as biomarkers. Enabling stratification of clinical populations, based on individual biological differences, to predict treatment response to pharmacological and non-pharmacological interventions. Here we consider the links between co-morbid metabolic syndrome and depression, focusing on biomarkers including leptin and ghrelin in combination with assessing gut microbiota composition, as a potential tool to help identify individual differences in depressed population.

Association between Sarcopenia and Depression in Patients with Chronic Liver Diseases

“…Depression is twice as frequent in diabetic patients compared with non-diabetic patients [46]. Psychiatric conditions are characterized by an increased risk of metabolic syndrome including dyslipidemia, obesity, hypertension, and hyperglycemia [45]. However, in our data, metabolic parameters such as HbA1c, BMI, and total cholesterol level were not significant factors associated with BDI-II ≥11.…”

“…Previous studies have found an increased prevalence of depressive symptoms in patients with metabolic disorders [44,45,46]. Depression is twice as frequent in diabetic patients compared with non-diabetic patients [46].…”

Melatonin regulates the neurotransmitter secretion disorder induced by caffeine through the gut-brain axis in zebrafish (Danio rerio)

“…Mice, zebrafish, dogs, chickens, pigs, and many types of other germ-free models have been appropriately used in various research studies to verify the link between the intestinal microbiota and some diseases [31][32][33][34][35] . As the importance of gut-brain axis in brain development has gradually been confirmed, germfree animals have gradually become an accepted model for gut-brain axis studies, which has become an important research means and valuable experimental tool for the study of the intestinal microbiota in host behaviour and various brain diseases [36][37][38][39] . In our validation experiment, the recovery of neurotransmitters in the GF group did not reach the level as in the normal zebrafish after adding the same dose of melatonin, indicating the key role of the intestinal microbiota in the regulation process of neurotransmitter secretion by melatonin, which subsequent real-time PCR again confirmed.…”

Gut–Brain Axis: Focus on Neurodegeneration and Mast Cells

“…Gut microbiome dysbiosis is responsible for the development of local and systemic inflammation, resulting in disintegration of the gut epithelial membrane, hyperpermeability, invasion of bacteria and viruses within the brain parenchyma, and, ultimately, neuroinflammation and dysfunction of neuronal cells. Several studies using GF animal models were conducted to investigate the interaction between gut microbiota and brain, and many of them showed increased BBB permeability compared to animals with normal gut flora [51][52][53].…”