Late Breaking Abstract - The effect of altering gut microbiota on the development of pulmonary hypertension

Background: Pulmonary arterial hypertension (PAH) is an intractable disease, the development of which may be related to the inflammatory system. Recently, abnormal characteristics of gut microbiota in a PAH rat model (Su/Hx) were reported, but it has not yet been clarified whether abnormality of microbiota is a cause or result of PAH, which is therefore the purpose of this study. Methods: Su/Hx was induced in Sprague Dawley rats by subcutaneous injection of the VEGF antagonist SU 5416 (30 mg/kg) and exposure to hypoxia (10% O2). Some Su/Hx rats were treated with antibiotics (ampicillin, vancomycin, neomycin, and metronidazole) (Su/Hx+ABx group). Control rats were kept in normoxia. Alteration of pulmonary vessels within the lungs was analyzed. Preliminarily, we also collected fecal samples of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Gut microbiomes were analyzed by 16S rRNA gene sequencing. Results: Right ventricular systolic pressure (RVSP) in control, Su/Hx, and Su/Hx+ABx groups was 27.8±5.1, 52.2±13.7, and 29.1±4.6 mmHg, respectively (control vs. Su/Hx: p=0.005; Su/Hx vs. Su/Hx+ABx: p=0.02; control vs. Su/Hx+ABx: p=1.0). The percentage of obstructed pulmonary arteries in the Su/Hx+ABx group was significantly lower than in the Su/Hx group (Su/Hx: 23.6±5.3; Su/Hx+ABx: 9.5±6.3; p=0.002). 16S rRNA gene sequence analysis revealed that the percentages of several bacterial species were significantly correlated with RVSP in the rats and the percentage of a bacterial species X was positively correlated with pulmonary vascular resistance (r=0.76, p=0.049) in CTEPH patients. In conclusion, altering gut microbiota could affect the development of pulmonary hypertension.