Gut Microbiota and Metabolome Changes in Three Pulmonary Hypertension Rat Models

Dysbiosis of the gut microbiota and metabolites is found in both pulmonary hypertension patients and pulmonary hypertension rodent models. However, the exact changes in gut microbiota during the development of pulmonary hypertension is unclear. The function of the gut microbiota is also ambiguous. Here, this study showed that the gut microbiota was disrupted in rats with hypoxia (Hyp)-, hypoxia/Sugen5416 (HySu)-, and monocrotaline (MCT)-induced pulmonary hypertension. The gut microbiota is dynamically changed during the development of Hyp-, HySu-, and MCT-induced rat pulmonary hypertension. The variation in the alpha diversity of the gut microbiota in Hyp-induced pulmonary hypertension rats was similar to that in rats with MCT-induced pulmonary hypertension and different from that in rats with HySu-induced pulmonary hypertension. In addition, six plasma biomarkers, His, Ala, Ser, ADMA, 2-hydroxybutyric acid, and cystathionine, were identified in Hyp-induced pulmonary hypertension rats. Furthermore, a disease-associated network connecting Streptococcus with Hyp-induced pulmonary hypertension-associated metabolites was described here, including trimethylamine N-oxide, Asp, Asn, Lys, His, Ser, Pro, and Ile.