A new study published in Bioengineered found that the gut microbiome and metabolome were affected in rat models of pulmonary arterial hypertension (PAH). It joins a growing number of studies that have shown a correlation between changes in the gut microbiota and chronic diseases including atherosclerosis, obesity, chronic obstructive pulmonary disease, and PAH.

The results of this study showed that a monocrotaline (MCT) injection induced PAH symptoms and had a significant decreasing effect on the α-diversity of the gut microbiota, compared to control animals. The MCT injection also led to disruptions in the metabolome, including the upregulation of 34 metabolites and the downregulation of 2. The administration of multiple doses of the calcium-sensing receptor antagonist NPS2143 partially abrogated the changes in the microbiota and reversed the modifications in the metabolome.

The study authors stated, “NPS2143 treatment attenuates changes in the gut microbiota and subsequent effects on the host metabolome in rats with PAH. The current study may provide important evidence and better understanding of molecular mechanisms, and help in development of novel drug targets and therapeutic treatments for PAH.”


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Twenty-four male Wistar rats were used in the experiment and divided into 3 groups: control, MCT, and MCT+NPS2143. The MCT and MCT+NPS2143 groups each received a single dose of MCT (55 mg/kg) on day 1. The MCT+NPS2143 group also received intraperitoneal injections of NPS2143 at 4.5 mg/kg/day on days 1 through 21. Fresh fecal samples were obtained and used for metabolomic profiling and genetic analysis of gut microbiota. 

Various bacterial species were identified in all 3 groups of rats, with all sharing the same dominating species. Changes to the bacterial composition were observed at the phylum, class, and genus levels, however.

The rats exposed to MCT showed a general increase in the pathogenicity of the gut bacteria. There were also changes observed in the expression of genes related to metabolism, cellular processes, human diseases, and environmental and genetic information processing in the MCT rats. The administration of NPS2143 resulted in decreased levels of pathogenic bacteria and also partially reversed the changes in gene expression.

Increasing numbers of studies have shown that the gut microbiota is involved in various metabolic pathways. This study identified 22 such pathways in the PAH model rats, with the hedgehog signaling pathway being the most affected. A number of correlations between the gut microbiota and host metabolome were also identified in the study.

Reference

Hong W, Mo Q, Wang L, et al. Changes in the gut microbiome and metabolome in a rat model of pulmonary arterial hypertension. Bioengineered. 2021;12(1):5173-5183. doi:10.1080/21655979.2021.1952365