Regulatory Gaps Plague At-Home Microbiome Tests

About four years ago, Stephanie Servetas, a microbiologist at the National Institute of Standards and Technology (NIST), and her colleagues set out on a unique quest: They planned to mail a poop sample to seven companies that offered at-home microbiome test kits.

Direct-to-consumer (DTC) microbiome tests have gained traction in recent times because of increasing evidence linking the microbiome to conditions such as cancer, obesity, and mental health.^1-3 Generally, DTC microbiome testing companies mail a home test kit—which costs anywhere between $100 and $1000—to consumers, who then mail back stool samples. Within a few weeks, the users receive a detailed report of their microbiome profiles, usually accompanied by information and recommendations on balancing the gut microbiome for optimum health.

However, many microbiome researchers worry about the reliability of these profiles. “There are at least two or three bloggers that sent their own stool sample to two different places and anecdotally said, ‘I didn't get the same results,’” said Servetas. This prompted her to dig deeper into DTC microbiome testing services.

The team used a stool sample that they had created for microbiome testing in 2019 after homogenizing and thoroughly processing samples from a healthy individual, as part of another project. They couriered three replicates of this fecal sample to the DTC companies.

When they received the results, there were major discrepancies within profiles generated by different labs.⁴ Additionally, while most companies consistently reported similar microbiome diversity across the three samples, one of them reported dramatically different results in one of the samples, indicating poor reproducibility within the companies. Servetas believes that the results highlight concerns expressed by microbiome researchers about the absence of rigorous oversight in DTC microbiome testing services.

One of the major concerns is that different companies may analyze the same samples using different methodologies, yielding inconsistent results. “[The test may look like] a one-step thing, but really it's at least five steps to go from sample to…the report that you get,” noted Servetas.

For instance, she noted that there are few shared standards for isolating genetic material, sequencing it, analyzing the sequences, or reporting the results. Several clinicians, researchers, scientists who run DTC companies, and legal experts argue that increasing transparency of workflows, standardizing methods, and setting clear guidelines about what microbiome profiles actually report could help consumers receive scientifically grounded insights into their gut health.

You shouldn't make huge life-altering changes after just one test. It’s important to understand that one test is just going to give you a snapshot.

—Stephanie Servetas, National Institute of Standards and Technology

Additionally, with at-home microbiome testing gaining popularity even as research catches up, some experts worry that the field risks outpacing the science that backs it. “We want to see that the science occurs first to justify use of [microbiome tests] and that they're used appropriately and in a way that is helpful for patients and not harmful for patients or consumers,” said Erik von Rosenvinge, a clinical gastroenterologist at the University of Maryland.

However, this concern about microbiome testing does not mean that researchers and clinicians do not believe in the science behind it. “We're not negative about microbiome-based diagnostic tests; we're actually excited about them,” said von Rosenvinge.

How do Gut Microbiome Tests Work?

Servetas was not surprised when they received distinct microbiome signatures from different companies for the same sample. “The first giveaway that they were probably going to be different…[was] the method variability that was apparent to me,” she said.

When they set out to investigate DTC companies, the researchers received kits requiring different sampling methods from all services. While some of them asked for a whole bowel movement applied to brushes or swabs and instructed users to add the sample to a buffer, some others asked for material on used toilet paper and to ship it “neat.” As instructed, Servetas and her team mailed the parcels back at room temperature, which may have encouraged diverse microbial growth, she noted.

Once the companies receive the stool sample, they isolate genetic material from it. Servetas believes that this is the major step where variability is introduced: Companies use different kits to isolate the genetic material. Scientists have previously shown that isolating DNA from the same sample using different methods could yield distinct microbiome abundance.⁵

Moreover, companies differ in the genetic material they extract from fecal samples. While some isolate DNA, others obtain RNA. All companies then employ a form of next-generation sequencing to estimate the microbial life present. Some carry out 16S rRNA sequencing focused on identifying bacterial species, while others rely on metagenomics to look for bacteria as well as other microbes.

BIOHM Health is one such company where sequencing aims to look for both bacteria and fungi, “because…they work together,” said Mahmoud Ghannoum, a mycobiome researcher at Case Western Reserve University and cofounder of BIOHM Health.

According to von Rosenvinge, it would be ideal if after analyzing the sequencing data, companies could validate their results with a reference. However, this is not straightforward. “It gets complicated because we don't even know what a normal microbiome is,” said von Rosenvinge.

To bridge this gap, last year, scientists at NIST released a human stool reference material containing precisely measured, analyzed, and characterized human feces suspended in an aqueous solution. They built this standard, which is available for purchase, by collecting stool samples from healthy adults with varying eating habits and characterizing hundreds of microbes and nearly as many microbial metabolites. (The reference sample that Servetas sent to the DTC companies is not this standard.)

At BIOHM Health, though, Ghannoum and his colleagues use their in-house microbiome profile for reference. They report the microbiome status of users by comparing it with that of healthy people. “What I mean by that [is] they are the right weight. They are not on drugs. They are not stressed,” explained Ghannoum. The team obtains this information via consumer-filled questionnaires detailing their lifestyle, antibiotic usage, and other factors.

In addition to generating a report with the users’ microbiome profiles, many companies, including BIOHM Health, also offer dietary and lifestyle advice on best balancing their microbiomes.

The Problem of Minimal Regulations and Standards in Microbiome Testing

According to Georgina Hold, a gut microbiome researcher at the University of New South Wales Sydney, “The promise of microbiome testing potentially is overplayed based on what it can currently deliver.” She emphasized that this concern is not limited to commercial testing, but the state of science in the field. Because while such testing could indicate the presence, absence, and abundance of friendly or pathogenic microbes and their potential function, Hold noted, “it's not about who's there, it's about what they're doing.”

Last year, Hold joined forces with dozens of other researchers and clinicians to pen a consensus statement highlighting the lack of regulations and standards in microbiome testing and recommendations for best practices to improve consistency and reliability.⁶

In addition to noting that labs that provide such services must be accredited and registered, the researchers also proposed that labs be transparent about test protocols and offered suggestions for reporting that would be most useful to the consumers. They also emphasized the need to make users aware of the benefits and pitfalls of microbiome testing.

Despite these efforts, “there is a big regulatory gap here,” said Diane Hoffmann, a health law professor at the University of Maryland. A few years ago, Hoffmann received a grant from the National Institutes of Health to investigate the ethical, legal, and social implications of the Human Microbiome Project.⁷

As part of this venture, Hoffmann and her colleagues examined companies providing DTC microbiome testing services across the globe. They also spoke to different stakeholders including microbiome researchers, clinicians, patients with chronic gut conditions, people who had undergone such tests, industry and consumer representatives, and bioethicists.

Their investigation revealed that DTC microbiome tests lack analytical validity that would ensure accurate detection and quantification of the intended analytes.⁸ Moreover, these tests are also not always clinically valid, given that they cannot accurately establish the presence or absence of a disease.

Additionally, while federal regulatory standards require a lab to test an unknown sample sent by a centralized agency for proficiency testing, “There's no proficiency testing that's actually done for these laboratories,” Hoffmann said.

Given this, Hoffmann and her colleagues highlighted the need for more federal oversight in DTC microbiome testing to protect users.

Bridging the Regulatory and Standardization Gap in Microbiome Tests

DTC microbiome testing companies generally follow a business model similar to that of DTC genetic testing companies. “[DTC genetic testing] has been a controversial and much debated area of regulation,” noted Hoffmann.

For a while, the Food and Drug Administration (FDA) did not regulate DTC genetic tests that provided information related to ancestry. But when these companies started offering testing for genetic predisposition to certain diseases, the FDA stepped in.

We want to see that the science occurs first to justify use of [microbiome tests] and that they're used appropriately and in a way that is helpful for patients and not harmful for patients or consumers.

—Erik von Rosenvinge, University of Maryland

“In vitro diagnostic devices (IVDs) are regulated by the FDA,” the FDA spokesperson wrote in an email to The Scientist. “IVDs are intended for use in the collection, preparation, and examination of specimens taken from the human body, such as blood, saliva, or tissue, for use in the diagnosis of disease or conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae.”

However, Hoffmann noted that DTC microbiome tests do not fall under this category: They would be considered wellness tests unless they claim to detect specific diseases.

“These tests are not to prevent, treat, or diagnose,” said Ghannoum. “These tests look at your microbiome and see what is [the] state of your microbiome compared to healthy people. We are not treating [people]; we just help them to rebalance their microbiomes.”

Ghannoum added that the field needs research like Servetas’s recent study to highlight standardization gaps in the field. Based on his past experience, he believes this gap can be bridged if experts come together.

A few years ago, Ghannoum chaired a committee at the Clinical and Laboratory Standards Institute to chalk reference guidelines for testing the susceptibility of fungi to antifungals. As part of this, his team obtained data from at least seven independent labs from distinct institutions to standardize reference methods in the field.⁹ “Unfortunately, in the microbiome [field], nobody has done that,” he said.

This could be fixed by following a pipeline similar to the one that their antifungal susceptibility committee followed and having a certain number of independent labs with expertise to agree upon a set of standards and guidelines. If such a committee is set in place, standards could be put in place within about two and a half years, said Ghannoum.

Based on Servetas’s interaction with some founders of DTC microbiome testing companies, she thinks such steps are feasible. “They are interested in engaging and saying, ‘Okay what can we do to get closer to [industry-wide standards],’” she noted. “There is industry interest from that point.”

Should One Get Their Microbiome Tested?

Despite issues in the field, the value of the global gut microbiome testing kit market soared to $1.2 billion in 2025. The value, projected to rise to $2.6 billion by 2035, indicates increasing consumer interest in understanding their microbiome profiles.

Von Rosenvinge said he understands why people may seek microbiome tests, especially if they suffer from chronic gut conditions. For instance, there is no single diagnostic test for irritable bowel syndrome, which could cause debilitating symptoms despite treatments. “You can envision how someone who is still having symptoms despite traditional treatments is going to go looking for further answers.”

However, he is not sure about the clinical significance when his patients consult him with their microbiome profiles. “I honestly don't know how to use that in a meaningful way,” he said.

Regardless of the regulatory gaps, Servetas said that for those who do end up getting their microbiomes tested, it would be better to stick to the same company for follow-up tests as they observed decent reproducibility within companies. “But you shouldn't make huge life-altering changes after just one test,” she cautioned. “It’s important to understand that one test is just going to give you a snapshot.”

Given that factors such as dietary and lifestyle choices constantly influence the microbiome, Hold agreed. “Depending on what day you took the test, [it] could really just be telling you that you ate this yesterday rather than what disease [you are] presenting with,” she said.

Despite the present limitations, von Rosenvinge is excited about microbiome profiling. “I'm optimistic that microbiome based diagnostic tests will eventually be helpful,” he said. However, at the moment, “we're not sure how best they can be used,” he said.