The Value Of Gut Microbiota In Pulmonary Arterial Hypertension
Posted Date: Jun 13, 2019
- Investigator: Arun Jose
- Specialties: Cardiovascular Disease, Heart Disease, Pulmonary Diseases
- Type of Study: Observational/Survey
Pulmonary arterial hypertension (PAH) is an uncommon vascular disease characterized by elevated pulmonary arterial pressures, which can lead to progressive right heart failure and death. Prognosis is primarily driven by the degree of right ventricular maladaptation and dysfunction, which has been associated with a number of biochemical changes including increased serum inflammatory markers, impaired cardiac metabolism, and increased intestinal edema and permeability. These changes may be driven by the systemic effects of Trimethylamine-N-Oxide (TMAO), an endogenous metabolite of the compound trimethylamine produced by intestinal microbes. TMAO has previously been linked to enhanced atherosclerosis, and is considered one of the primary mediators of intestinal microbiota influence on cardiovascular diseases. One of the main drivers of elevated TMAO levels is thought to be changes in the levels of gut microbial species, including an alteration of the ratio of Firmicutes to Bacteroidetes (F/B), which has been linked to the development of a number of diseases including chronic kidney disease, obesity, and cardiovascular disease. The intestinal microbiota has recently been theorized to also contribute to the pathogenesis PAH, where increased intestinal permeability leads to bacterial overgrowth and translocation, alterations in the F/B ratio, TMAO overproduction, systemic inflammation, metabolic dysfunction, and ultimately pulmonary vascular remodeling. Abnormalities in the intestinal microbiota composition and F/B ratio have also been observed in rat models of PAH, but no study to date has investigated the composition of the intestinal microbiota or its significance to human PAH. The primary objective of this study is to explore the association between pulmonary vascular disease and the intestinal microbiota composition in humans. We postulate that patients with PAH will have a distinct intestinal microbiological signature, and a significantly higher F/B intestinal bacterial ratio, as compared to control patients without significant pulmonary vascular disease. Completion of this study will provide new insight into the pathogenesis of PAH, and may eventually lead to new diagnostic tests and possibly even new treatments for PAH.
Criteria:
All Adult Non-Obese Patients With A Diagnosis Of Group 1 Pulmonary Arterial Hypertension (Pah) Are Eligible For This Study
Keywords:
Pulmonary Hypertension, Microbiome, Gut
For More Information:
Arun Jose
513-558-7451
josean@ucmail.uc.edu