Study Links Gut Bacteria Changes to More Severe PAH in Patients

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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The composition of certain bacteria in the gut is significantly altered and associated with greater disease severity in people with pulmonary arterial hypertension (PAH), a pilot study shows.

These findings add to prior research in PAH patients and animal studies linking the disease to an altered gut microbial community, or microbiota, and support further investigation into the significance and effects of a PAH-specific gut microbiota, researchers say.

The study, “A unique gut microbiota signature in pulmonary arterial hypertension (PAH): a pilot study,” was published in the journal Pulmonary Circulation.

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Gut microbiota comprises the vast community of friendly bacteria, fungi, and viruses that colonize the gastrointestinal tract. This community helps to maintain a balanced gut function, protect against disease-causing organisms, and influence a person’s immune system.

A well-balanced gut microbiota depends on several factors, such as diet, age, antibiotic therapy, and certain diseases. A gut microbiota imbalance (dysbiosis) has been shown to trigger or worsen a number of health conditions, ranging from gastrointestinal diseases to respiratory, cardiovascular, and inflammatory disorders.

PAH is a progressive disease characterized by high blood pressure in the blood vessels that supply the lungs, making the right ventricle of the heart work harder to pump blood. Continuous strain on the right ventricle can ultimately lead to heart failure.

Heart failure in PAH has been previously associated with higher levels of pro-inflammatory molecules, impaired fat and protein metabolism, and increased intestinal swelling and permeability. A higher gut permeability may allow microbes and toxins to pass through the intestinal wall into the bloodstream.

“These metabolic and biochemical changes are believed to be driven in-part by alterations in composition of the intestinal microbiome,” which have been observed in both animal models of PAH and people with heart failure, the researchers wrote.

While a previous study reported a unique gut bacterial profile in PAH patients, with a low number of beneficial bacterial species relative to healthy people, these abnormalities “have yet to be validated or studied in a comprehensive fashion,” the researchers wrote.

To shed more light on this matter, researchers at the University of Cincinnati analyzed the gut microbiota of 20 adults with stable PAH and 20 cohabitating, healthy adult family members.

The team also investigated potential associations between gut microbiota changes and PAH severity, as assessed with several validated measures, including pulmonary vascular resistance (PVR), median pulmonary artery pressure (mPAP), and the maximum distance walked in six minutes.

Patients were recruited from a single center between July 2019 and April 2021. The researchers noted healthy family members served as controls to minimize potential influencing effects caused by genetic variation, diet, or living environment.

Also excluded from the study were obese individuals, those with lung or cardiovascular disease, and those taking antibiotics or immunosuppressive medications in the preceding three months, or probiotics in the preceding week.

Stool samples were collected and analyzed through a genetic sequencing method to determine the composition and diversity of their gut microbiota.

Most participants (83%) were white, and 90% of patients were women versus 35% in the control group. The median age was 53 years for patients and 52 for controls. Half of the patients had idiopathic PAH, or PAH of unknown cause.

Results showed that gut microbiota richness and diversity were generally similar between PAH patients and controls, which is in contrast with previous studies reporting a reduced diversity in people with PAH or cardiovascular diseases relative to healthy controls.

“This inconsistency may be explained by the multitude of potentially confounding factors known [to] affect the composition of the intestinal microbiome” and that “are not consistently accounted for in microbiota clinical research studies,” the researchers wrote.

However, people with PAH showed a significant deficiency in one bacterial species, Lachnospiraceae bacterium GAM79, relative to healthy relatives.

This bacterium belongs to a group of bacteria called Firmicutes, which are thought to contribute to a healthy gut and anti-inflammatory responses. In addition, Lachnospiraceae produce certain molecules thought to have “a protective effect against cardiovascular diseases,” the researchers wrote.

While there was no strong or reproducible link between disease severity and the global microbial abundance in the gut of patients, several bacterial species were associated with PAH severity.

Specifically, a higher relative abundance of Anaerostipes Rhamnosivorans and a relative deficiency of Amedibacterium Intestinale, Ruminococcus bicirculans, and Ruminococcus albus species were linked to worse blood flow dynamics (higher PVR and mPAP) and a shorter six-minute walk distance.

All three deficient species also belong to Firmicutes, suggesting that a reduction in beneficial gut bacteria is associated with more severe PAH.

“It is possible that specific intestinal gut microbes, such as the ones identified in our study as associated with more severe PAH disease, exert their effects on the pulmonary vasculature through pro-inflammatory intermediaries,” the team wrote.

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These findings support further investigation “into the presence, significance, and potential physiologic effects of a PAH-specific intestinal [microbiota],” including the complex relationship between gut microbiota and the levels of circulating by-products in PAH, they added.

Also, “given the complexity of intestinal microbial regulation, these future studies should be designed to minimize the effect” of potential influencing factors, the researchers wrote.

Among the study’s limitations, the team noted that cardiopulmonary testing, as a measure of disease severity, was not performed at the time of stool sample collection, which might have affected results.