It Takes a Village: Diverse Gut Microbes Linked to Arterial Health in Women

Having a healthy ecosystem of gut bacteria may be protective against arterial aging, a new observational study out of the United Kingdom suggests.

Researchers led by Cristina Menni, PhD (King’s College London, England), have found a correlation between diversity of the gut microbiome and arterial stiffness. The results were published online last week in the European Heart Journal.

Some of the bacteria’s effect seems connected to insulin resistance, visceral fat, and C-reactive protein (CRP). However, “the vast majority of the effect is not mediated by these mechanisms,” senior author Ana Valdes, PhD (NIHR Nottingham Biomedical Research Centre, England), noted to TCTMD via email. “We hypothesize, given the strong links between low microbiome diversity and inflammatory diseases such as eczema, psoriasis, and [inflammatory bowel disease], that the microbiome must be modulating inflammation in other ways not reflected by CRP.”

If the magnitude of the effect seen here is confirmed by additional studies, it’s likely that these differences in gut microbial composition would impact event rates in women, she predicted. But for now, Valdes said, the implications for clinical practice are limited.

Allison Reiss, MD (NYU Winthrop Hospital, Mineola, NY), commenting on the research for TCTMD, described it as a “very well-done, elegant study” that considered many possible reasons why arterial stiffness could occur and got rid of the “background noise” of potential confounders.

“What they’re saying is you have to think outside the box” in terms of the mechanism behind cardiovascular disease, she told TCTMD. Sometimes it’s unclear why a particular patient—who is otherwise healthy—would have a heart attack, for example. “Cardiologists really know this. They can clean [up] everything as nicely as they can for a patient, try to optimize everything, and still the progression of cardiovascular disease [occurs]. So, clearly we’re missing something,” Reiss observed. “Maybe something we’re missing is from the microbiome.”

It’s all one big system. Sometimes we get too caught up in local things. Allison Reiss

Beyond inflammation, “there might be something more” to how gut bacteria might be having this effect, she said. Reiss’ own research, for example, focuses on microRNA and how the microbiome communicates with the rest of the body. Whatever the mechanism, “it’s something to do with [the fact] that a healthy body has a healthy, diverse microbiome,” Reiss commented, adding, “It’s all one big system. Sometimes we get too caught up in local things.”

Jennifer Pluznick, PhD (Johns Hopkins School of Medicine, Baltimore, MD), who also commented on the study for TCTMD, said she was “very intrigued” by its findings.

“I think there have been a number of studies over the past few years that have had incremental advances that have slowly but surely argued that there’s definitely some sort of connection between the gut microbiota and blood pressure control in general,” she observed. “But this is the first study in humans that I’ve seen that looked at pulse-wave velocity, or arterial stiffness.”

Effect Largely Independent of Other Risk Factors

Menni et al studied 617 women enrolled in the TwinsUK registry, measuring arterial stiffness using carotid-femoral pulse wave velocity (PWV) and microbiome composition using fecal samples.

There was a negative correlation between PWV values and the diversity of the gut microbiome both overall and for seven specific types of bacteria.

Microbe diversity accounted for an estimated 8.3% of variation in PWV among the women. Results were consistent when taking into account things like diet, smoking, alcohol consumption, socioeconomic status, medication use, and uric acid levels. The link remained significant after adjusting for various metabolites generated by gut bacteria, including indolepropionate, phenylacetylglutamine, and trimethylamine oxide, which has been tied to poor outcomes in patients with ACS.

To TCTMD, Pluznick pointed out that the bacteria-produced metabolites can affect the “host” in different ways. One of the bacteria types the authors identified as influential, for instance, produces butyrate, “a compound that we know can have some effects on receptors that play roles in blood pressure control. So, I can imagine ways that could be involved, but we definitely need a lot more work before we can draw straight lines between things,” Pluznick noted, adding that the three metabolites assessed in this analysis are not the only ones out there.

After adjusting for age, body mass index, and mean arterial pressure, the researchers found that only 5.5% of the bacteria’s effect on PWV was mediated by insulin resistance, visceral fat, C-reactive protein, and CV risk factors.

Sauerkraut, Yogurt, and Fiber

“Given the possibility of modifying the gut microcomposition via diet and probiotic supplementation, this opens therapeutic avenues for reducing arterial stiffness targeting the gut microbiome,” Menni and colleagues conclude, noting that this is the first time the gut microbiome had been linked to arterial stiffness in this way.

Fiber intake is already recommended as part of dietary guidelines, so these findings aren’t a departure from current advice, they point out. “In fact, the gut microbiome composition may contribute to the mechanism whereby dietary fiber intake influences cardiovascular risk, which has yet to be fully elucidated.”

Valdes said that beyond seeing if these findings can be replicated in other cohorts, the investigators also want to explore whether the gut microbiome has any influence on measures of CVD risk, like atherosclerotic plaque, or on CVD events. “An important avenue of research with potential therapeutic implications is identifying the molecular mediators of decreased arterial stiffness (and presumably CVD risk) that are produced or influenced by the gut microbiome,” she said.

Improving the microbiome, Reiss said, might well lead to lower cardiovascular risk. For now, though, it’s impossible to know whether taking steps to raise microbial diversity in the gut would have that effect. Clinicians should simply “stay tuned,” she advised.

If patients ask about how to get better gut bacteria, the best approach is diet, Reiss said. “The problem is we’re not really at the point of knowing how to manipulate the microbiome so clearly. There’s all kinds of supplements on the market, and I don’t have much faith in them. . . . Really, it’s the sauerkraut and the yogurt: eating a good diet that’s full of either the foods for bacteria, or the bacteria themselves.”

Eventually, the goal is to have easy tests for assessing patients’ microbiome at the doctor’s office. “We’re not there yet. It’s onerous to get stool and do these things. We’re not doing it routinely,” Reiss said, calling the study a “harbinger of things to come” that reinforces the idea that knowing more about the microbiome could guide care.

In terms of next steps, Pluznick suggested it would be useful to see whether these findings extended to men. If the patterns are inconsistent, that might help tease out mechanisms. Other possibilities, such as whether there are immune system changes happening in relation to bacteria differences, also can be explored, she said.