In the JournalsPerspective

Gut bacteria linked to PAH

Mohan Raizada
Mohan Raizada

New data published in Hypertension have shown that a unique profile of gut bacteria can predict the presence of pulmonary artery hypertension in patients with 83% accuracy.

“We showed for the first time that specific bacteria in the gut are present in people with PAH. 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,” Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida College of Medicine in Gainesville, said in a press release.

In their study, Raizada and colleagues isolated and sequenced microbiota DNA from stool samples of 18 patients with PAH and from a reference group of 12 people without a history of cardiopulmonary disease or PAH risk factors.

Results revealed taxonomic and functional changes in the gut microbial communities of the PAH cohort compared with the reference cohort. Specifically, the researchers noted increases in pathways for the synthesis of arginine, proline and ornithine in patients with PAH as well as increases in groups of bacterial communities associated with trimethylamine/trimethylamine N-oxide (TMA/TMAO) and purine metabolism, whereas the reference cohort displayed increases in butyrate- and propionate-producing bacteria, including Coprococcus, Butyrivibrio, Lachnospiraceae, Eubacterium, Akkermansia and Bacteroides.

New data published in Hypertension have shown that a unique profile of gut bacteria can predict the presence of pulmonary artery hypertension in patients with 83% accuracy.
Source: Adobe Stock

In light of these differences, the researchers also sought to identify bacteria most strongly associated with PAH by applying random forest modeling to the two cohorts. The model predicted the presence or absence of PAH based on the composition of the gut microbiome with 83% accuracy, as compared with accuracy of 50% or less if no relationship between the gut microbiome and PAH existed.

“We were very surprised to see such an association within a small group of study subjects,” Raizada said. “It usually requires hundreds of patients to achieve significance.”

Although gut bacteria are known to change based on a variety of factors, Raizada noted that the bacteria linked to PAH do not seem to change, stating that he and colleagues believe that “these particular bacteria are constant.”

If validated in larger studies, these data also suggest that the unique bacterial profile of patients with PAH may help create novel approaches to diagnosis, management and treatment, according to the researchers.

However, there are still more opportunities for research, Raizada said.

“There is still the question of whether the specific microbiota associated with PAH is the cause or the result of the disease; therefore, more research is needed,” he said in the release.

Further, it remains unknown the effect these gut bacteria may have on the lungs in patients with PAH, according to Raizada.

“We do not know if and how gut bacteria and viruses make their way to the lungs,” he 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.” – by Melissa Foster

Disclosures: The authors report no relevant financial disclosures.

Mohan Raizada
Mohan Raizada

New data published in Hypertension have shown that a unique profile of gut bacteria can predict the presence of pulmonary artery hypertension in patients with 83% accuracy.

“We showed for the first time that specific bacteria in the gut are present in people with PAH. 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,” Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida College of Medicine in Gainesville, said in a press release.

In their study, Raizada and colleagues isolated and sequenced microbiota DNA from stool samples of 18 patients with PAH and from a reference group of 12 people without a history of cardiopulmonary disease or PAH risk factors.

Results revealed taxonomic and functional changes in the gut microbial communities of the PAH cohort compared with the reference cohort. Specifically, the researchers noted increases in pathways for the synthesis of arginine, proline and ornithine in patients with PAH as well as increases in groups of bacterial communities associated with trimethylamine/trimethylamine N-oxide (TMA/TMAO) and purine metabolism, whereas the reference cohort displayed increases in butyrate- and propionate-producing bacteria, including Coprococcus, Butyrivibrio, Lachnospiraceae, Eubacterium, Akkermansia and Bacteroides.

New data published in Hypertension have shown that a unique profile of gut bacteria can predict the presence of pulmonary artery hypertension in patients with 83% accuracy.
Source: Adobe Stock

In light of these differences, the researchers also sought to identify bacteria most strongly associated with PAH by applying random forest modeling to the two cohorts. The model predicted the presence or absence of PAH based on the composition of the gut microbiome with 83% accuracy, as compared with accuracy of 50% or less if no relationship between the gut microbiome and PAH existed.

“We were very surprised to see such an association within a small group of study subjects,” Raizada said. “It usually requires hundreds of patients to achieve significance.”

Although gut bacteria are known to change based on a variety of factors, Raizada noted that the bacteria linked to PAH do not seem to change, stating that he and colleagues believe that “these particular bacteria are constant.”

If validated in larger studies, these data also suggest that the unique bacterial profile of patients with PAH may help create novel approaches to diagnosis, management and treatment, according to the researchers.

However, there are still more opportunities for research, Raizada said.

“There is still the question of whether the specific microbiota associated with PAH is the cause or the result of the disease; therefore, more research is needed,” he said in the release.

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Further, it remains unknown the effect these gut bacteria may have on the lungs in patients with PAH, according to Raizada.

“We do not know if and how gut bacteria and viruses make their way to the lungs,” he 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.” – by Melissa Foster

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Christine Lee

    Christine Lee

    This study shows a possible correlation between specific gut microbiome and PAH, but the study was small and needs a larger scale, case-controlled, prospective, clinical trial for validation. It is too early to assume direct cause and effect at this time.  This study was limited to 18 PAH patients and 13 reference patients. Other variables could have had an impact on the outcome. Many variables (e.g., ethnicity, age, other medical comorbidities, diet, geographic location of living, climate, etc.) can influence gut microbiomes.  More research is needed to determine if altering gut bacteria will have a role that would directly impact PAH. Is it a cause and effect or is it just the effect - i.e., does having PAH create an environment that invites the chances of certain bacteria to thrive and populate with ease? Hopefully, future studies will elucidate this further.

    • Christine Lee, MD
    • Gastroenterologist
      Digestive Disease & Surgery Institute
      Cleveland Clinic

    Disclosures: Lee reports no relevant financial disclosures.