From the Journals

Study implicates gut bacteria in PAH

Model finds microbiota highly predictive



A unique collection of bacteria in the gut may have a strong association with pulmonary arterial hypertension and could be highly predictive of the disease in undiagnosed patients, according to a study published in the journal Hypertension.

Dr. Mohan Raizada

This is the first study to show that people with PAH have a common specific gut microbiota profile, wrote lead study author Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida, Gainesville.

The findings have the potential to change how cardiologists diagnose and treat PAH, he added. “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,” Dr. Raizada said.

The researchers developed a model that found the specific microbiota profile was 83% accurate in predicting the presence or absence of PAH. If a larger study can validate the findings, the researchers wrote, this could lead to a new test for diagnosing PAH that’s less invasive than cardiac catheterization. It could also lead to new treatments that target the gut microbiome.

Study investigators collected stool samples from 18 PAH patients and 12 people without a history of cardiopulmonary disease. The microbiota DNA from the stool samples were isolated and sequenced. The analysis revealed that PAH patients had reduced richness and evenness of the gut bacteria, known as alpha diversity. They had increased levels of bacteria associated with atherosclerosis, and healthy patients had increased levels of bacteria that produced short-chain fatty acids.

Although recent studies have begun to show potential associations between the gut microbiome and cardiovascular diseases, this research is in its infancy, Mariell Jessup, MD, commented. “Even though the study by Dr. Raizada and colleagues predicted pulmonary arterial hypertension based on an individual’s microbiome with some accuracy, it is an observational study, so it does not prove cause and effect. Many other factors, especially diet, affect the gut microbiome,” added Dr. Jessup, Chief Science and Medical Officer for the American Heart Association.

Dr. Mariell Jessup

She stressed that, “In addition, even if studies confirm an association between the gut microbiome and cardiovascular diseases such as PAH, more research is needed to determine if improving gut microbiota could directly impact PAH or other cardiovascular diseases. The findings of this study will not impact clinical practice.”

Dr. Raizada and his coinvestigators offered two possible mechanisms through which the gut microbiome influences pulmonary physiology. One is that lower levels of bacteria that produce the short-chain fatty acid butyrate, such as Coprococcus, Butyrivibrio, Lachnospiraceae, and Eubacterium, along with Clostridia in the gut of PAH patients, may increase gut permeability. Reduced butyrate weakens gut barrier function and can induce inflammation and leakage. This can allow microbial metabolites to enter the circulatory system, disrupting metabolism and immunity and affecting pulmonary vessels.

The second potential mechanism is that increased Collinsella in the PAH cohort may be the culprit that increases gut permeability, resulting in the ensuing gut barrier dysfunction and inflammation. The study noted Collinsella contributed most of the increased genes for the biosynthesis on the amino acid proline in these patients, and that a previous study implicated Collinsella and its parent, Cariobacteriales, in trimethylamine/trimethylamine N-oxide production (TMA/TMAO) in atherosclerosis (Cell. 2015;163[7]:1585-95). The non-PAH patients had higher levels of bacteria that had a low correlation with TMA/TMAO.

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

More research is needed to determine if the specific microbiota associated with PAH causes the disease or is a result of it, they concluded.

The study was funded by grants from the National Institutes of Health, the NIH National Center for Research Resources, and the U.S. Department of Defense. Dr. Raizada and coauthors reported no relevant financial relationships.

SOURCE: Raizada MK et al. Hypertension. 2020. doi: 10.1161/HYPERTENSIONAHA.119.14294.

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