The educational content in this post, elaborated in collaboration with Biocodex Microbiota Institute, was independently developed and approved by the GMFH publishing team and editorial board.
While a common gut microbiome signature has been defined across unrelated diseases, a healthy gut microbiome is yet to be defined
The current interest shown by companies in offering direct-to-consumer microbiome tests is rooted in the changes in gut microbiome composition or functions linked to almost every chronic disease.
A recent analysis of the fecal microbiomes of 8,200 Dutch individuals has revealed a shared common gut microbiome signature across unrelated diseases, including cancer, cardiovascular diseases, gastrointestinal diseases, neuropsychiatric conditions and other conditions such as skin problems and autoimmune disorders.
In a course recently launched by Xpeer with unrestricted grant of Biocodex Microbiota Institute on detection, prevention and treatment of gut microbiome dysbiosis in the clinical setting, consultant in gastroenterology and member of the GMFH World Summit’s Scientific Committee Francisco Guarner has updated some features of an altered gut microbiome that include:
- Low microbial richness or diversity,
- Depletion of short chain fatty acid-producing bacteria, and
- Instability in composition over time.
Decreased diversity does not always mean an unhealthy gut microbiome. For instance, a major increase in dietary fiber can temporarily decrease gut microbiome diversity due to an enrichment of microbes specifically involved in degrading plant carbohydrates, but that does not negatively affect human health. The same happens with the low diversity shown by the gut microbiome of breastfed infants as a result of specific bacteria being selected for degrading human milk oligosaccharides in breast milk, which is beneficial for infant health.
Another challenge in microbiome research that mostly relies on feces for studying gut microbial activity is that scientists still cannot define a healthy gut microbiome.
As Amy Loughman and Heidi M Staudacher at the Food & Mood Centre at Deakin University in Australia wrote in a recent perspective in The Lancet Gastroenterology & Hepatology: “The known unknowns of the microbiome are staggering: approximately 20% of bacterial gene sequences have not been identified and 40% of the 10 million genes remain unknown with respect to their function.”
“The ‘ideal’ microbiome has not been identified and is likely very individual for each person,” says Kate Scarlata, MPH, RDN, a world-renowned gastrointestinal dietitian who specializes in food intolerance and digestive health.
Every person has the microbiome they deserve, meaning the gut microbiome of each individual has been selected from all the microbes they have encountered during their lifetime. It is unique to each person and is relatively stable and resilient, so it is difficult to predict if someone would benefit from a specific gut microbiome composition or from changing their current gut microbiome to a new composition.
Types of microbiome tests based on what they look for
An important first question that should be asked before choosing a microbiome test is what information the tests provide depending on the methods used as microbiome researcher Lucy Mailing explains in her science blog.
Culture-based tests are not accurate as they favor oxygen-loving bacteria, most of which are pathogens, while missing bacteria that grow without oxygen, which include the vast majority of gut commensals.
That means that culture-dependent characterization of gut microbes under aerobic conditions misses most of the microbes contained in the stool and shows pathogens in concentrations that are higher than their actual amounts. Simply put, easy to grow does not mean most important or abundant. To overcome that limitation, emerging technologies such as culturomics (high-throughput cultivation of anaerobic microbes) are being developed.
The second major type of microbiome test is molecular-based stool tests based on DNA characterization instead of microbe isolation. They include various test types:
- 16S rRNA gene sequencing: if the test is based on sequencing the 16S ribosomal ribonucleic acid present in all bacteria, it will only identify the bacteria at the genus level (and not species nor strain).
However, the gut microbiome is more than just the bacteriome. Archaea, fungi, protozoa, phages and viruses are also members of the microbiome that are usually overlooked in these type of microbiome tests.
- Targeted or quantitative PCR: this test is more sensitive and accurate than 16S, as it can identify the microbes it is targeting to the species level, which includes not only bacteria, but also parasites, fungi and viruses, as long as it targets each microbe of interest.
- Metagenomics: this test uses deep sequencing to identify the abundance of microbes down to the strain level and provides an estimate of the functions of microbes (what could happen).
- Meta-transcriptomics and metabolomics: these are the most advanced tests moving beyond composition to study activity of the gut microbes, with transcriptomes on fecal samples measuring microbial mRNA (what is likely to happen) and the metabolome giving information on microbial metabolites (what is happening).
However, the vast majority of metabolites measured in human blood and feces remain unknown. Although they are widely used in the research setting when moving beyond studying composition to focus on gut microbial activity, they offer little value for the healthcare provider today.
Francisco Guarner summarized the current status of microbiome tests as follows: “Existing microbiome tests today use different techniques and focus on taxonomy. Most of them provide little information for diagnostic or prognostic purposes.”
When could fecal microbial signatures offer potential therapeutic benefits?
Experts agree it is too soon to know what the information provided by microbiome tests means. “While interesting, microbiome stool testing is a bit ahead of its time to be marketed to consumers presently,” says Kate Scarlata.
She adds: “Some stool microbiome tests offer information beyond the microbes in the stool such as stool fat (to assess if fat malabsorption is present) or stool elastase (a marker for adequate pancreatic enzyme production) but these specific tests can be easily run by a health care provider and are often covered by insurance, unlike these ‘full-service’ stool microbiome tests which can cost the consumer a lot of cash.”
While microbiome testing is in its infancy and it is difficult to figure out what to do with the results, particular metrics might be useful in the near future for guiding some clinical decisions.
For instance, some research has shown that the gut microbiome might help discriminate between responders and non-responders to dietary interventions in patients with irritable bowel syndrome or obesity.
Other pilot studies have shown the potential of fecal microbial signatures to predict the response to biological treatment in patients with inflammatory bowel diseases or for colorectal cancer screening.
While there is a long way to go before implementing the tests in clinical practice, it is too early to systematically recommend a routine microbiome test for guiding clinical decisions and steering patients towards specific solutions such as including or excluding foods or recommending specific probiotics or prebiotics based on information provided by microbiome tests.
As a takeaway for patients who have been living with gut issues for a while and are interested in gut microbiome testing as an answer to their problems, Kate Scarlata recommends working with a gastroenterologist or gastrointestinal dietitian, while being wary of “practitioners” who offer stool tests. As microbiome tests are still in their infancy, Kate Scarlata encourages patients not to fall prey to practitioners who offer rigid protocols based on stool microbiome analysis.
References:
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Loughman A, Staudacher HM. Treating the individual with diet: is gut microbiome testing the answer? Lancet Gastroenterol Hepatol. 2020; 5(5):437. doi: 10.1016/S2468-1253(20)30023-6.
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