Changes in the gut microbiome and metabolome in a rat model of pulmonary arterial hypertension

ABSTRACT

The gut microbiota is widely considered to be involved in several diseases, including atherosclerosis, obesity, chronic obstructive pulmonary disease (COPD) and pulmonary arterial hypertension (PAH). This study aimed to determine if changes in the gut microbiome and metabolome play a major role in the early pathogenesis of PAH. Male Wistar rats were injected with monocrotaline (MCT) (55 mg/kg) at day 1 and injected with calcium-sensing receptor (CaSR) antagonist NPS2143 (4.5 mg/kg/d) from days 1 to 21. Fecal samples were obtained. The gut microbiota and metabolome were analyzed by 16S rRNA gene sequencing and mass spectrometry-based analysis to investigate the effect of PAH in this rat model. MCT injection had a marked effect on the composition of the gut microbiota. This finding was further confirmed by metabolomic analysis with identification of several metabolites relevant to the gut microflora. However, NPS2143 partially abrogated this intestinal flora disorder and reversed fecal metabolite abnormalities. In conclusion, our study shows correlations between changes in the gut microbiome and the metabolome in PAH, which are affected by NPS2143.

Graphical abstract

KEYWORDS:

• Pulmonary arterial hypertension
• gut
• microbiome
• metabolome

Highlights

The gut microbiome is altered in rats with PAH.

The fecal metabolome is altered in rats with PAH.

Correlation in alteration of gut microbiota and the host metabolome through NPS2143 treatment in PAH rats.

Acknowledgements

Rats in this study were obtained from the Experimental Animal Center of Guangdong (Guangdong, China). Approval of animal care and experiments was issued with the Animal Care and Use Committee of Guangzhou Medical University (Approval No. GY2019-064) and in accordance with the principles and guidelines of the National Institutes of Health.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01S155), Natural Science Foundation of Guangdong (2021A1515011024, 2020A1515010264), National key Research and Development program of China (2016YFC1304100, 2016YFC1304104), Characteristic Innovation Projects of Universities in Guangdong Province (2019KTSCX139), Science and Technology Program of Guangzhou (202102080045, 202102020980, 202002030080), Guangdong Province Key Field R&D Program (2020B1111330001), ZHONGNANSHAN MEDICAL FOUNDATION OF GUANGDONG PROVINCE (ZNSA-2020003), Open Project of the State Key Laboratory of Respiratory Disease (SKLRD-Z-202103 and SKLRD-QN-201913) and The doctoral fund of the third affiliated hospital of Guangzhou Medical University (2019B07)