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Microbiota and the control of blood-tissue barriers.

ABSTRACT: The gastro-intestinal tract is an ecosystem containing trillions of commensal bacteria living in symbiosis with the host. These microbiota modulate a variety of our physiological processes, including production of vitamins, absorption of nutrients and development of the immune system. One of their major functions is to fortify the intestinal barrier, thereby helping to prevent pathogens and harmful substances from crossing into the general circulation. Recently, effects of these microbiota on other blood-tissue barriers have also been reported. Here, we review the evidence indicating that gut bacteria play a role in regulating the blood-brain and blood-testis barriers. The underlying mechanisms include control of the expression of tight junction proteins by fermentation products such as butyrate, which also influences the activity of histone deacetylase.

SUBMITTER: Al-Asmakh M

PROVIDER: S-EPMC4574894 | biostudies-other | 2015 Jul-Sep

REPOSITORIES: biostudies-other

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Project description:Cerebrospinal fluid (CSF) and brain tissue sodium levels increase during migraine. However, little is known regarding the underlying mechanisms of sodium homeostasis disturbance in the brain during the onset and propagation of migraine. Exploring the cause of sodium dysregulation in the brain is important, since correction of the altered sodium homeostasis could potentially treat migraine. Under the hypothesis that disturbances in sodium transport mechanisms at the blood-CSF barrier (BCSFB) and/or the blood-brain barrier (BBB) are the underlying cause of the elevated CSF and brain tissue sodium levels during migraines, we developed a mechanistic, differential equation model of a rat's brain to compare the significance of the BCSFB and the BBB in controlling CSF and brain tissue sodium levels. The model includes the ventricular system, subarachnoid space, brain tissue and blood. Sodium transport from blood to CSF across the BCSFB, and from blood to brain tissue across the BBB were modeled by influx permeability coefficients P BCSFB and P BBB , respectively, while sodium movement from CSF into blood across the BCSFB, and from brain tissue to blood across the BBB were modeled by efflux permeability coefficients PBCSFB' and PBBB' , respectively. We then performed a global sensitivity analysis to investigate the sensitivity of the ventricular CSF, subarachnoid CSF and brain tissue sodium concentrations to pathophysiological variations in P BCSFB , P BBB , PBCSFB' and PBBB' . Our results show that the ventricular CSF sodium concentration is highly influenced by perturbations of P BCSFB , and to a much lesser extent by perturbations of PBCSFB' . Brain tissue and subarachnoid CSF sodium concentrations are more sensitive to pathophysiological variations of P BBB and PBBB' than variations of P BCSFB and PBCSFB' within 30 min of the onset of the perturbations. However, P BCSFB is the most sensitive model parameter, followed by P BBB and PBBB' , in controlling brain tissue and subarachnoid CSF sodium levels within 3 h of the perturbation onset.

Project description:BackgroundThe microbiota interacts with the brain through the gut-brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive episodes, and how it was modulated by treatment.MethodsIn this case-control multiomic study, we analyzed the blood microbiome composition, inferred bacterial functions and metabolomic profile of 56 patients experiencing a current major depressive episode and 56 matched healthy controls, before and after treatment, using 16S rDNA sequencing and liquid chromatography coupled to tandem mass spectrometry.ResultsThe baseline blood microbiome in patients with a major depressive episode was distinct from that of healthy controls (patients with a major depressive episode had a higher proportion of Janthinobacterium and lower levels of Neisseria) and changed after antidepressant treatment. Predicted microbiome functions confirmed by metabolomic profiling showed that patients who were experiencing a major depressive episode had alterations in the cyanoamino acid pathway at baseline. High baseline levels of Firmicutes and low proportions of Bosea and Tetrasphaera were associated with response to antidepressant treatment. Based on inferred baseline metagenomic profiles, bacterial pathways that were significantly associated with treatment response were related to xenobiotics, amino acids, and lipid and carbohydrate metabolism, including tryptophan and drug metabolism. Metabolomic analyses showed that plasma tryptophan levels are independently associated with response to antidepressant treatment.LimitationsOur study has some limitations, including a lack of information on blood microbiome origin and the lack of a validation cohort to confirm our results.ConclusionPatients with depression have a distinct blood microbiome and metabolomic signature that changes after treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients who are experiencing a major depressive episode.

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Microbiota and the control of blood-tissue barriers.

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