What Patients Can Do Now
Advances in the field of microbiome research — and the related “gut health” wellness craze — have spawned all kinds of new microbiome-based products: Like over-the-counter probiotic supplements and at-home test kits, which let you send a stool sample for analysis to reveal microbiome health and personalized diet recommendations.
But the science behind these tests is still evolving, said Dr. Damman. “The clinical inferences and applications are still pretty limited.”
For most people, the first step to fostering healthier microbial metabolites is much simpler: Diversify your diet.
“A lot of folks are missing that diversity,” Dr. Damman said.
“Eat foods and experiment with foods that you might not eat all the time,” especially fruits, vegetables, nuts, seeds, and beans.
Another strategy: Eat foods with probiotic bacteria. “I view it as an insurance policy,” said Dr. Versalovic, “fortifying my gut with probiotics, with daily yogurt, for example, at breakfast.”
Fermented foods like kimchi and kombucha can also increase microbial diversity and can even contain health-promoting postbiotics, research shows.
As for probiotic supplements, the jury’s still out.
Certain strains of probiotic bacteria may be beneficial for some patients, like those with diarrhea, Crohn’s disease, and irritable bowel syndrome, according to World Gastroenterology Organisation guidelines.
As with other interventions, individual responses can vary. A Stanford study showed that some people with metabolic syndrome improved when taking a probiotic, while others didn’t. Both groups had key differences in gut bacteria and dietary habits.
For best results, such microbiome-based interventions will need to be personalized, experts say. And the technology to do that is coming sooner than you might think.
Microbiome’s Medical Future: ‘We Are on the Cusp of a New Era’
In just a few years, artificial intelligence (AI) models could predict gut microbial composition based on data such as dietary habits and household characteristics, Dr. Kumar said.
Advancements in metabolomics and bioinformatics could soon help physicians and patients personalize their treatment approaches, said Dr. Damman.
One focus will be on fortifying the gut with whatever it lacks.
“In those individuals where certain microbes are missing, (a) how could we add them back potentially in a rational, science-driven way, and (b) maybe some of those factors that the microbes are producing out the other ends, you could give directly,” said Dr. Damman.
For example, multiple companies make butyrate as a dietary supplement, although the research is too early to support widespread use. Another option could be eating something that spurs butyrate production. One small study found that a fiber supplement formulated to increase butyrate levels in the colon reduced participants’ systolic blood pressure by an average of six points.
Another option could be synbiotics, products that combine bacteria and the food source they feed on. “If you just give a diet-based therapy, it is not going to work as much. Because what if that diet needs certain bacteria to have these beneficial metabolites?” said Ashutosh Mangalam, PhD, associate professor of pathology at the University of Iowa Carver College of Medicine, Iowa City.
Dr. Mangalam studies links between bacterial metabolism of phytoestrogens in soy foods and multiple sclerosis (MS) development. He is using AI to understand differences in metabolites in patients with MS vs healthy controls to determine how to target them.
Gut microbial metabolites could also affect disease screening and intervention. What if gut microbe sequencing could predict a pregnant person’s risk of developing depression, something now assessed through simple questionnaires?
“Imagine that your doctor says, ‘Okay, give me a poop sample,’ ” Dr. Bernabé said. “Then they phenotype it, and then they put it in your electronic medical record, and they say, ‘Well, you have high likelihood of having a mood disorder down the line in your pregnancy. Why don’t we directly refer you to a provider now so you can follow up?’ ”
Research is already underway to understand how metabolites might be linked to pregnancy outcomes, complex regional pain syndrome, and anxiety. Researchers are also investigating whether supplementing our diets with things like prebiotic fibers, apple polyphenols, or tomato paste might influence metabolites. And fecal transplants that shift the gut microbiome and metabolites could have potential in diseases like unexplained atherosclerosis, post-COVID syndrome, and hidradenitis suppurativa.
Dr. Hazen’s discovery linking TMAO with cardiovascular risk has already changed clinical practice. A blood TMAO test can help identify patients at risk who may not have traditional risk factors. “Millions have been done,” Dr. Hazen said.
Meanwhile, his drug targeting the TMAO pathway inches closer to clinical trials.
“In an animal model, we elicit improvement in heart failure, renal disease, atherosclerosis, thrombosis, aortic aneurysm, and obesity,” Dr. Hazen said. The first clinical trials will focus on renal disease.
As with any drug, the road to approval takes time. And success is not guaranteed.
But Dr. Hazen for one is optimistic.
“We are on the cusp of a new era,” Dr. Hazen said. “Like when humans first discovered insulin and glucagon were hormones that impact sugar metabolism. We now recognize myriad new ‘hormones’ in the form of gut microbiome metabolites that impact our physiology and susceptibility to diseases.”
A version of this article first appeared on Medscape.com.