Gut Microbiota May Be Linked to Inflammation in CTEPH Patients

Margarida Maia PhD avatar

by Margarida Maia PhD |

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The gut microbiota of patients with chronic thromboembolic pulmonary hypertension (CTEPH) differs from that of healthy individuals, and this perhaps explains why there also is more inflammation, a Japanese study found.

The findings provide new information on the way CTEPH may develop.

The study, “Altered gut microbiota and its association with inflammation in patients with chronic thromboembolic pulmonary hypertension: a single-center observational study in Japan,” was published in the journal BMC Pulmonary Medicine.

CTEPH is caused by blood clots forming in the blood vessels of the lungs. When the blood clots do not dissolve, they can lead to a buildup of scar tissue. This blocks normal blood flow, causing an abnormally high pressure in the blood vessels of the lungs and making the right side of the heart work harder.

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How CTEPH develops is unclear, but inflammation may play a role. Previous work has shown that blood clots in patients with CTEPH are rich in inflammatory cells, such as lymphocytes, neutrophils, and macrophages.

Other work has shown that animals and people with pulmonary arterial hypertension, which is caused by a narrowing of the blood vessels of the lungs, have an abnormal gut microbiota. The gut microbiota refers to the collection of all microorganisms living in the gut. Some microorganisms, such as certain bacteria, can bring about inflammation.

To know if an abnormal gut microbiota also is present in people with CTEPH, researchers in Japan collected samples of stool from patients and healthy individuals. Then, they watched for differences in the type of bacteria found in the samples. 

The study included 11 patients (seven women, four men) who received a diagnosis of CTEPH at Chiba University Hospital in Japan and 22 healthy individuals (14 women, eight men). Their mean age was 65.5 years.

Of the 11 patients, eight (72.7%) were already taking soluble guanylate cyclase stimulators to lower pressure in the blood vessels of the lungs. After their diagnosis, all were started on anticoagulants to thin the blood and prevent it from clotting.

First, the researchers watched for differences in inflammatory cytokines, which are chemical signals sent by certain immune cells to trigger inflammation. Compared with healthy individuals, patients with CTEPH had significantly higher levels of tumor necrosis factor alpha, interleukin 6, interleukin 8, and macrophage inflammatory protein 1 alpha in the blood.

They also had about three times higher levels of endotoxin, a component of the cell membrane of certain bacteria that can be released from the gut into the bloodstream to trigger inflammation. The levels of endotoxin correlated with those of inflammatory cytokines. This means that the higher the levels of endotoxin, the higher those of inflammatory cytokines.

Next, the researchers analyzed the stool samples using 16S rRNA sequencing, a technique that allows them to identify which types of bacteria are present. They also used bioinformatics to help them tell how much variety there was in the samples.

They found that the gut microbiota of CTEPH patients was significantly less varied than that of healthy individuals. Specifically, bacteria of the genuses Faecalibacterium, Roseburia, and Fusicatenibacter were less abundant in the gut of patients with CTEPH than in a healthy gut. These bacteria are known to play a role in reducing inflammation and protecting the gut.

A so-called random forest model to distinguish the gut microbiota of patients with CTEPH from that of healthy individuals had an accuracy of 80.3%.

“The analysis of gut microbiota might become a new tool for detecting [pulmonary hypertension], including CTEPH,” the researchers wrote.

While the sample size was relatively small and it remained unclear whether the changes in gut microbiota were a cause or a result of CTEPH, “the composition of the gut microbiota in patients with CTEPH was distinct from that of healthy participants, which may be associated with the elevated inflammatory cytokines and endotoxins in CTEPH,” the researchers concluded.