an-vivo-method-for-evaluating-gut-blood-barrier-liver-metabolism

An <em>In Vivo</em> Method for Evaluating the Gut-Blood Barrier and Liver Metabolism of Microbiota Products

The gut-blood barrier (GBB) controls the passage of nutrients, bacterial metabolites and drugs from intestinal lumen to the bloodstream. The GBB integrity ...

Medical University of Warsaw

Hydrogen sulfide, a toxic gas, at low concentrations is also a biological mediator in animals. In the colon, hydrogen sulfide is produced by intestinal tissues and gut sulfur bacteria. Gut-derived molecules undergo liver metabolism. Portal hypertension is one of the most common complications contributing to the high mortality in liver cirrhosis. We hypothesized that the colon-derived hydrogen sulfide may affect portal blood pressure. Sprague-Dawley rats were maintained either on tap water (controls) or on water solution of thioacetamide to produce liver cirrhosis (CRH-R). Hemodynamics were measured after administration of either saline or NaS, a hydrogen sulfide donor, into (1) the colon, (2) the portal vein, or (3) the femoral vein. Expression of enzymes involved in hydrogen sulfide metabolism was measured by RT-PCR. CRH-R showed a significantly higher portal blood pressure but a lower arterial blood pressure than controls. Saline did not affect hemodynamic parameters. In controls, intracolonic hydrogen sulfide decreased arterial blood pressure and portal blood flow but increased portal blood pressure. Similarly, hydrogen sulfide administered into the portal vein decreased arterial blood pressure but increased portal blood pressure. In contrast, hydrogen sulfide administered into the systemic vein decreased both arterial and portal blood pressures. CRH-R showed significantly greater responses to hydrogen sulfide than controls. CRH-R had a significantly higher liver concentration of hydrogen sulfide but lower expression of rhodanese, an enzyme converting hydrogen sulfide to sulfate. In conclusion, colon-administered hydrogen sulfide increases portal blood pressure while decreasing the systemic arterial blood pressure. The response to hydrogen sulfide is more pronounced in cirrhotic rats which show reduced hydrogen sulfide liver metabolism. Therefore, colon-derived hydrogen sulfide may be involved in the regulation of portal blood pressure, and may contribute to portal hypertension. Impact statement Accumulating evidence suggests that gut-derived molecules affect the control of the circulatory system. Mechanisms controlling liver circulation have been profoundly studied; however, the effects of gut bacteria-derived molecules on portal blood pressure have not been established. In the colon, hydrogen sulfide is produced by intestinal tissues and gut sulfur bacteria. We found that colon-administered hydrogen sulfide increases portal blood pressure while decreasing the systemic arterial blood pressure. The hemodynamic response to hydrogen sulfide was more pronounced in cirrhotic rats which showed reduced hydrogen sulfide liver metabolism, i.e. lower expression of rhodanese, an enzyme converting hydrogen sulfide to sulfate. We propose that colon-derived hydrogen sulfide may affect the regulation of portal and arterial blood pressures and may be involved in portal hypertension.

Colonic hydrogen sulfide produces portal hypertension and systemic hypotension in rats.

Portal hypertension (PH) is a potentially life-threatening condition. We investigated the effects of indole and dietary tryptophan, a substrate for gut bacterial production of indole, on portal blood pressure (PBP), portal blood flow (PBF), and arterial blood pressure (ABP) in Sprague-Dawley rats (SD) and SD with PH induced by liver cirrhosis (SD-PH). Hemodynamics were recorded in anesthetized male 28-wk-old SD and SD-PH at baseline and after the administration of either a vehicle or indole into the colon. Blood levels of tryptophan and its bacterial metabolites were evaluated using chromatography coupled with mass spectrometry. Indole at lower doses increased PBP and PBF. Indole at higher doses produced a transient increase in PBP, which was accompanied by a decrease in ABP. Portal blood levels of indole, indole-3-propionic, indole-3-lactic, and indole-3-acetic acids were higher in SD-PH, suggesting an increased gut-blood barrier permeability. Rats on a tryptophan-rich diet showed a significantly higher PBP and portal blood level of indoles than rats on a tryptophan-free diet. In conclusion, a tryptophan-rich diet and intracolonic indole increase PBP and portal blood level of indole. Rats with PH show an increased penetration of indoles from the colon to the circulation. Intracolonic indole production may be of therapeutic importance in PH.

Maksymilian Onyszkiewicz

Department of Experimental Physiology and Pathophysiology,
Laboratory of Centre for Preclinical Research,
Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research

Medical University of Warsaw

An In Vivo Method for Evaluating the Gut-Blood Barrier and Liver Metabolism of Microbiota Products

Maksymilian Onyszkiewicz

Department of Experimental Physiology and Pathophysiology,Laboratory of Centre for Preclinical Research,Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research

Medical University of Warsaw

An In Vivo Method for Evaluating the Gut-Blood Barrier and Liver Metabolism of Microbiota Products

Department of Experimental Physiology and Pathophysiology,
Laboratory of Centre for Preclinical Research,
Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research