Diet, Exercise, and Gut Bacteria Play Different, Overlapping Roles in Cardiometabolic Disease Development

PRAGUE, Czech Republic—After days of discussion related to cholesterol science and the clinical management of atherosclerosis, the last morning of the 2017 European Atherosclerosis Society meeting turned the spotlight on risk factors beyond lipids that might play a role in disease genesis.

Summarizing a session devoted to cardiometabolic risk factors beyond lipids, session co-chair Stephen Nicholls, MBBS, PhD (University of Adelaide, Australia), told TCTMD that while it’s no secret that diet and exercise play a role in the development of cardiovascular disease, the messaging around them needs to be simplified in order to have a clinical impact,

The challenge with diet—which Nicholls called the “most important of risk factors”—is that the ongoing scientific debate over whether fat or sugar plays a larger role in the development of disease, while worthwhile, is “obstructing the pathway to improving the dietary pattern in the whole community,” he said. “My patients say to me, ‘Is it that I'm eating too much fat or too much sugar?’ I say, ‘You're probably eating too much, period.’”

My patients say to me, ‘Is it that I'm eating too much fat or too much sugar?’ I say, ‘You're probably eating too much, period.’ Stephen Nicholls

Dietary messaging needs to be distilled down to a “simple, deliverable bit of advice that doesn't polarize,” Nicholls recommended. In other words, this means adhering to a message that cannot be eventually manipulated into “a cover of Time magazine saying, ‘You guys had it all wrong,’” he added, referring to a now infamous article about butter published in 2014.

Quality Matters

In his presentation during the session, Qi Sun, MD, ScD (Harvard Medical School, Boston, MA), said the key to promoting a healthy diet is focusing on “quality, quality, quality.”

Based on the current evidence, “a healthy diet should include high consumption in whole grains, fruits and vegetables, nuts, and legumes, and should be moderate in alcohol consumption. It should be low in refined grains, red or processed meats, and sugar-sweetened beverages,” he summarized. “In addition, it is possible to further improve the diet quality by cooking at home from scratch or using a healthier cooking method to prepare meals.”

People don’t eat ingredients in isolation, Sun added, so those in charge of promoting healthy eating patterns need to keep that in mind.

Nicholls agreed. It will be up to clinicians and public health officials to disseminate this definition of quality in a “relatively simple way,” he said.

As for how the field of nutrition can move along scientifically, Sun said “we really need to marry the evidence from the clinical trials with those from good solid observational studies to make comprehensive assessment of evidence in totality.”

Exercise Important Beyond Weight Loss

With exercise, the key factor that clinicians need to communicate is that it provides additional benefits over weight loss, said presenter Patrick Schrauwen, PhD (Maastricht University, the Netherlands).

“It’s really hard to lose body weight by increasing physical activity,” he said, noting that running an hour burns about the same amount of energy in a bag of potato chips. “And [the bag of chips] goes way faster.”

This is one of the reasons why “exercise and physical activity have been neglected a little bit, and that is really wrong,” Schrauwen emphasized. “Even though you don’t lose a lot of weight and it's not easy to lose weight with physical activity, it’s well-known that exercise has so many benefits. . . . Increasing the level of your energy expenditure by exercise can boost your metabolic health, it can decrease the lipid content of the liver, of the heart, [and] it can improve insulin sensitivity.”

Even though you don’t lose a lot of weight and it's not easy to lose weight with physical activity, it’s well-known that exercise has so many benefits. Patrick Schrauwen

The precise amount and type of exercise needed to achieve these benefits is still not clear, however. But, he said, other data have suggested that shivering as a result of cold exposure and reducing sedentary time also “can have an effect on the turnover of lipids and ectopic fat.”

In response to a question regarding body mass index (BMI), Schrauwen said that less focus should be paid to this measure and more to the overall patient. “Not everyone that has a high BMI also develops diabetes,” he said. “Some people try to be active and try to live healthy even though it’s so hard to lose weight. That needs also to be stimulated. You should not only focus on losing weight; some people can be healthy even if overweight.”

Harnessing the Microbiome

A new, emerging field of thought among cardiometabolic researchers is that the microbiome—defined as the bacteria living in a particular environment, in this case the human gut—might play a role.

“One of the main differences between the microbiome and the human genome is that the microbiome can change over time whereas our own genome is relatively stable,” presenter Fredrik Bäckhed, PhD (University of Gothenburg, Sweden), explained. While factors like pharmaceuticals and temperature can have an impact on the human microbiome, diet is “the main driving factor,” specifically dietary fiber. Because the microbiome will produce metabolites that interact with what we eat, Bäckhed said he views it as an “endocrine organ.”

Prior studies about the microbiome in obesity have been smaller and inconsistent, but it is known that obese people tend to have less diverse microbiota than nonobese people, he summarized. This could be because these individuals eat a less diverse diet or ingest less dietary fiber, but this is still unknown, he added.

Its interaction with cardiovascular disease specifically has also been examined. Researchers have found that most bacteria in atherosclerotic plaque that is “completely different” from what is found in the oral cavity and GI system, Bäckhed explained. Notably, however, there have been a few species identified in the plaque that are also found primarily in the mouth and also the gut, suggesting that some of these bacteria may migrate.

Additionally, research has shown that plasma levels of trimethylamine N-oxide (TMAO)—a product of the breakdown of certain dietary nutrients by gut bacteria—are independently associated with atherosclerotic burden in CAD patients.

While the microbiome cannot “explain everything, . . . we do see that it may contribute to atherosclerosis by several different pathways” Bäckhed concluded.

We do see that [the microbiome] may contribute to atherosclerosis by several different pathways. Fredrik Bäckhed

“Watch this space,” Nicholls implored. “The breakthroughs and the advances in the last decade that have shown how the bugs that normally live in your gut influence metabolism and health across a range of organs is just fantastic. It begs the question about how they set you up for risk and your response to different exposures in the first place. . . . From the science perspective, I think that's the coolest.”

Next, researchers in this field will have to present deliverable action items for how manipulating the microbiome could have clinical outcomes, he said. “I think that's where the next 10 years are.”

For now, it is important to realize the importance of your own microbiome, Nicholls said. “Your gut and the bugs that reside within it are clearly an important factor in metabolic abnormalities, diabetes, and cardiovascular disease.”