Study Identifies Gut Bacteria That May Be Linked to PAH

“We showed for the first time that specific bacteria in the gut are present in people with PAH,” Mohan Raizada, PhD, professor at the University of Florida College of Medicine and lead author of the study, said in a press release. “While current PAH treatments focus on the lungs, looking at the lung/gut axis could open the door to new therapies centered in the digestive system.”

While PAH is typically associated with the respiratory system, it also has characteristics of a systemic disease involving different systems and organs. Those include the central nervous system (brain and spinal cord), immune system, heart, and kidneys.

The gut and its resident microorganisms — the so-called gut microbiome — may also be involved. The gut and the lungs share many common features. Both are in contact with the environment, so smoking, toxins, and infections are common risk factors for disease.

Moreover, both have diverse microbiota, and imbalances in these microorganism populations may contribute to diseases such as cystic fibrosis (CF) and asthma.

There is a lack of information regarding the potential role of the gut microbiome in the development of PAH, so researchers at the University of Florida College of Medicine set out to investigate whether PAH patients could have a unique gut microbiome profile that might be involved in the development of the disease.

They collected stool samples from 18 type 1 PAH patients and 12 healthy people with no history of cardiopulmonary disease or PAH risk factors. The DNA of the microorganisms in the fecal microbiome was then isolated, sequenced, and analyzed.

Results showed that PAH patients had a distinct gut bacterial profile, with less diversity and a low number of beneficial bacterial species, compared with controls. This specific bacterial profile was able to predict the presence or absence of PAH with 83% accuracy.

Moreover, some of the bacterial communities that were altered in patient stool samples produce metabolites found in abnormal levels in PAH patients. Those included the amino acid (a protein building block) arginine. According to the researchers, “these data suggest the potential roles of enzymes and amino acids produced by the gut microbiota in PAH and cardiovascular disease risk.”

“We do not know if and how gut bacteria and viruses make their way to the lungs,” Raizada said. “Some studies have pointed to an increased incidence in intestinal leakage among people with pulmonary hypertension, which may allow some intestinal bacteria to get into the bloodstream and circulate to the lungs where they can cause inflammation and lead to vascular changes.”

The team also analyzed the gut viral population, noting that “viruses play an important regulatory role in the gut ecosystem.” Their analysis showed a depletion in Lactococcal phages and enrichment in Enterococcus phages in PAH patients, suggesting a potential regulatory role of the gut viral population in the gut microbiome of individuals with PAH. Phages are viruses that infect bacteria.

“Identification and characterization of PAH-specific bacteria and metabolites in both gut and lung hold promise for the development of innovative strategies for the control and treatment of PAH by modification of diet, prebiotics, microbiota transplantation, and pro/antibiotics,” the researchers said.

More research is needed to determine if particular gut microbiota found to be associated with PAH could be the cause or the result of the disease, Raizada said.