Possible reason found for persistent high cardiovascular risk in Cushing’s

Imbalance in gut microbiome ID'd as likely cause in new study

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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People with Cushing’s disease who have been in remission for years may have an imbalance in their gut microbiome — the group of all microorganisms living in the gut — and this may be the reason why their cardiovascular risk persists, a pilot study suggests.

The small study included only women, but the researchers noted the relationships they found between gut microbiome imbalance and several metabolic parameters associated with cardiovascular risk were exclusively seen among Cushing’s patients and not in the healthy female participants who served as controls.

“We have demonstrated for the first time that patients with [Cushing’s disease] in long-term remission have significant gut [microbiome imbalance],” the team wrote.

The study, “Gut microbial dysbiosis in patients with Cushing’s disease in long-term remission. Relationship with cardiometabolic risk,” was published in the journal Frontiers in Endocrinology.

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Looking for links between cardiovascular risk and gut microbiome

For people in a healthy state, there is a diverse and balanced community of bacteria and other microbes in the gut that help digest food and protect the body against harmful germs. Many factors, such as a poor diet, stress, and certain medications and diseases, can disturb this balance.

Gut dysbiosis occurs when there is an imbalance that causes an overgrowth of harmful bacteria and disturbs the gut’s normal function. Its effects can be even more widespread because the gut microbiome interacts with other systems in the body, including the cardiovascular one.

Cushing’s occurs when there is too much cortisol, a hormone that helps the body respond to stress. Cortisol works to tone down inflammation, regulate metabolism, and control blood pressure. Too much cortisol, however, may bring about a range of symptoms, including cardiovascular problems.

It is important for people with Cushing’s to be aware of their increased cardiovascular risk. Even when in remission, patients may experience high blood pressure, called hypertension, and be at an increased risk of having blood clots form. They also may have dyslipidemia, which is an excess of fatty molecules circulating in the bloodstream, and have a higher risk of death from cardiovascular disease.

Now, a team of researchers in Spain investigated whether there’s a link between gut dysbiosis and cardiovascular risk in people with Cushing’s who had been in remission, meaning their symptoms were under control, for at least five years.

The study included 28 women with Cushing’s, with a mean age of 51, who had been in remission for a median of 11 years. As controls, the study included 24 healthy women of about the same age and with a similar body mass index — a measure of a person’s weight relative to height.

Compared with the healthy women, those with Cushing’s had higher levels of glycosylated hemoglobin, a measure of blood sugar, over the previous couple of months. They also had higher levels of triglycerides, a type of fat, in the blood and fibrinogen — a protein that helps blood clots to form.

Alpha diversity, a measure of how diverse the gut microbiome is, was lower in stool samples from women with Cushing’s, indicating that they had fewer types of bacteria and other germs in their gut.

An analysis of beta diversity, which compares samples to see how much they differ from each other, revealed that those from women with Cushing’s clustered together and differed from control samples.

Bacteria of the genus Collinsella, Actinomyces, or Streptococcus and an unknown genus from Coriobacteriaceae were abundant in samples from women with Cushing’s, but were almost absent from control samples. In turn, Sutterella and Lachnospira bacteria were almost absent in women with Cushing’s.

“Patients with [Cushing’s disease] in long-term remission have significant gut dysbiosis, characterized by lower abundance and diversity of [the gut microbiome] as compared with healthy controls,” the researchers wrote.

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Further study needed with more Cushing’s patients

In women with Cushing’s, but not in healthy women, alpha diversity was positively associated with fibrinogen levels and inversely correlated with blood sugar and triglyceride levels.

Alpha diversity was also inversely correlated with the HOMA-IR index, a measure of insulin resistance, which occurs when cells stop responding to the hormone insulin, which helps control blood sugar levels.

“Sustained dysmetabolism [an imbalance in measures of cardiovascular health] in patients who have been previously exposed to high cortisol levels may be related to gut dysbiosis,” the researchers wrote.

Because the study’s sample size was relatively small, the team noted that “future studies with a larger sample are needed to confirm our results and establish the potential benefits of specific interventions aimed at changing [the gut microbiome] in [Cushing’s disease] patients.”