Lactobacillus Restructures the Micro/Mycobiome to Combat Inflammation-Mediated Right Ventricular Dysfunction in Pulmonary Arterial Hypertension

作者：Sasha Z. Prisco, Madelyn Blake, Felipe Kazmirczak, Ryan Moon, Benjamin P. Kremer, Lynn M. Hartweck, Minwoo Kim, Neal Vogel, Jenna B. Mendelson, Daphne Moutsoglou, Thenappan Thenappan, Kurt W. Prins · 发表于：Circulation Heart Failure · 年份：2025 · DOI：10.1161/circheartfailure.124.012524 · 被引用次数：9 · 研究领域：Pulmonary Hypertension Research and Treatments、Cardiac Fibrosis and Remodeling、Cardiovascular Function and Risk Factors

BACKGROUND: Inflammation suppresses right ventricular (RV) function in pulmonary arterial hypertension (PAH). In particular, we showed GP130 (glycoprotein-130) signaling promotes pathological microtubule remodeling and RV dysfunction in rodent PAH. Emerging data demonstrate the intestinal microbiome regulates systemic inflammation, but the impact of modulating the gut microbiome on the GP130-microtubule axis in RV failure is unknown. METHODS: Two weeks following monocrotaline injection, rats were administered daily Lactobacillus rhamnosus (4×10 7 colony-forming units) via oral gavage for 10 days. Next-generation metagenomics and internal transcribed spacer 2 sequencing delineated fecal bacterial and fungal compositions. SomaScan proteomics measured levels of 7596 serum proteins. RV immunoblots quantified protein abundances. Light or super resolution confocal microscopy assessed RV, lung, and jejunal morphology. Echocardiography and invasive closed-chest pressure-volume loops evaluated PAH severity and RV function. The relationship between Lactobacillus abundance and RV function was assessed in 65 patients with PAH. RESULTS: Lactobacillus administration restructured both the intestinal micro- and mycobiome. The alteration in the gut ecosystem improved intestinal health as demonstrated by increased jejunal villus length and glycocalyx thickness and diminished intestinal permeability biomarkers. Serum proteomics revealed Lactobacillus modulated systemic inflammation and decrease...