Are Direct-to-Consumer Microbiome Tests Clinically Useful?

 Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.

"We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs," one says. "Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby's biomarkers.…Any family member like dads or siblings are welcome too," says another.

The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.

Clinical Implications, Not Applications

The microbiome is the " constellation of microorganisms that call the human body home," including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.

Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.

But lack of scientific evidence and validity hasn't stopped a growing number of companies across the globe from offering direct-to-consumer (DTC) microbiome tests, Erik C. von Rosenvinge, MD, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, told Medscape Medical News.

"If you go to their websites, even if it's not stated overtly, these companies at least give the impression that they're providing actionable, useful information," he said. "The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they're receiving any benefit."

von Rosenvinge and colleagues authored a recent article in Science arguing that DTC microbiome tests "lack analytical and clinical validity" — and yet regulation of the industry has been "generally ignored." They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.

Unreliable, Unregulated

The lack of reliability has been shown by experts who have tested the tests.

"People have taken the same stool sample, sent it to multiple companies, and gotten different results back," von Rosenvinge said. "People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it's hard to use it in any clinical way."

Test users' methods and the companies' procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, told Medscape Medical News.

"So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it's preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they're using to amplify the signals and which bioinformatic pipeline they use are also important," said Kao, who presented at the recent Gut Microbiota for Health World Summit.

Different investigators and companies use different technologies, so it's very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the Dermatology and Pathology Departments at the Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.

The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, told Medscape Medical News.

"Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations," said Ghannoum, who is a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by von Rosenvinge and colleagues, as noted above.

Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn's disease as a model. Their strategy involved the following steps:

• Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
• Gaining insight into the interactions among the identified pathogens.
• Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
• Creating a prototype formulation for testing.
• Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
• Conducting clinical testing.

Ghannoum recommends that companies use a similar process "to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry."

Potential Pitfalls

Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results "is where the danger can really come in," Kao said. "There is still so much we don't know about which microbial signatures are associated with each condition."

"Even when we have a solution, like the Crohn's exclusion diet, a physician doesn't know enough of the nuances to give advice to a patient," she said. "That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that's not ethical. I'm pretty sure there's always going to be some kind of conflict of interest."

Supplements and probiotics are generally safe, but negative consequences can occur, von Rosenvinge noted.

"We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system," he said.

Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.

What to Tell Patients

"Doctors should be advising against this testing for their patients," gastroenterologist Colleen R. Kelly, MD, Brigham and Women's Hospital, Boston, told Medscape Medical News. "I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance."

"Recommendations to purchase probiotics or supplements manufactured by the testing company to 'restore a balanced or healthy microbiome' clearly seem like a scam," she added. "I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome."

von Rosenvinge said that the message to patients "is that the science isn't there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like."

When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, von Rosenvinge said.

"Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine," he said. "We don't have a single test that says, yes, you have irritable bowel syndrome, or no, you don't. We might suggest things that are helpful for some people and are less helpful for others."

Kelly said she worries that "there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn't mean we know what to do with them."

She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.

Educate Clinicians, Companies

More education is needed on the subject, so we can become "microbial clinicians," Kao said.

"The microbiome never came up when I was going through my medical education," she said. But we, and the next generation of physicians, "need to at least be able to understand the basics."

"Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions," Kao added.

As for clinicians who are currently ordering these tests and products directly from the DTC companies, Kao said, "I roll my eyes."

Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.

"Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations," he said.

von Rosenvinge, Kao, and Kelly had no relevant conflicts of interest. Ghannoum is a cofounder of BIOHM.

https://www.medscape.com/viewarticle/are-direct-consumer-microbiome-tests-clinically-useful-2024a10007yy