An imbalanced gut microbiome in people with pulmonary arterial hypertension (PAH) may generate increased concentrations of the proinflammatory microbial metabolite trimethylamine, along with lower levels of anti-inflammatory circulating short-chain fatty acids and secondary bile acids, according to a new study published in the American Journal of Respiratory and Critical Care Medicine.

A team of researchers from the University of Minnesota, Minneapolis, conducted a cohort study investigating the microbiome of patients living with PAH, their family members, and individuals with no health issues. To gain insight into the composition and metabolic output of gut microbiota, they tested participants’ stool samples using 16S ribosomal ribonucleic acid gene and shotgun metagenomics sequencing techniques, as well as analyzed their plasma samples for markers of inflammation, gut permeability, and microbial metabolites.

The results revealed that the lack of gut microbiome diversity in people with PAH corresponds to their pulmonary vascular disease severity. The copies of gut microbial genes responsible for the production of short-chain fatty acids and secondary bile acids were reduced in PAH patients, as well as the relative abundances of species encoding the same genes. Furthermore, the PAH patients’ plasma levels of these anti-inflammatory microbial metabolites were lower in comparison with the control groups. 


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On the other hand, the species containing microbial genes that encode the proinflammatory microbial metabolite trimethylamine were overrepresented in the samples taken from patients living with PAH.

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Upon analyzing the samples, the researchers found a substantial distinction between the healthy volunteers microbiome and that of the PAH patient group. However, the discrepancy in data derived from patients with PAH and their family controls was not as sizeable, as they tend to cohabitate.

“It is possible that gut dysbiosis either initiates PAH or facilitates the progression of already established PAH by calibrating immune responses,“ Moutsoglou and colleagues noted. “These findings support investigating modulation of the gut microbiome as a potential treatment for PAH.“

Perivascular inflammation and subsequent pulmonary vascular remodeling are considered the key pillars of PAH pathogenesis. However, the exact mechanism initiating and perpetuating immune dysregulation is not yet fully unraveled.

Reference

Moutsoglou DM, Tatah J, Prisco SZ, et al. Pulmonary arterial hypertension patients have a proinflammatory gut microbiome and altered circulating microbial metabolites. Am J Respir Crit Care Med. 2022 Nov 7. doi:10.1164/rccm.202203-0490oc.