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.
Scientists have not yet been able to define a single healthy gut microbiome profile
The current interest shown by patients suffering from gut ailments in testing their stool samples is rooted in the changes in gut microbiome composition or functions linked to almost every chronic disease.
But while a shared common gut microbiome signature has been found across unrelated diseases (i.e., cancer, cardiovascular diseases, gastrointestinal diseases, neuropsychiatric conditions and other conditions such as skin problems and autoimmune disorders), causation remains mostly unresolved.
In a course recently launched by Xpeer, with an unrestricted grant from the 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, which include:
- Low microbial richness or diversity,
- Depletion of short chain fatty acid-producing bacteria, and
- Instability in composition over time.
However, decreased gut microbe diversity does not always mean an unhealthy gut microbiome. For instance, a patient following a mostly plant-based diet can temporarily show a decrease in gut microbiome diversity. That is caused by an enrichment of microbes specifically involved in degrading plant carbohydrates but is not a negative health hallmark. 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 known to be beneficial for infant health.
As Colin Hill from APC Microbiome Ireland and the School of Microbiology at University College Cork (Ireland) recently stated in a perspective: “You have the microbiome you deserve”. Simply put, the gut microbiome 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.
The different types of microbiome tests currently available, based on methods for studying gut microbes
Today analysis of the gut microbiome is based on microbe isolation through culture-dependent characterization and DNA extraction through culture-independent characterization.
If a microbe grows easily in a test setting, that does not necessarily mean it is the most abundant or important in the fecal sample. In that regard, culture-based tests are inaccurate 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. To overcome that limitation, emerging technologies such as culturomics (high-throughput cell culture of bacteria) are being developed in an effort to isolate anaerobic microbes from the human gut.
The second major type of microbiome test is molecular-based stool tests using DNA based methods, such as next generation sequencing of 16S ribosomal RNA genes or whole genome shotgun sequencing, with the latter allowing inference of gut microbiota functions.
It is also feasible to measure metabolic products of the microbiome either in stool or serum using metabolomic methods, although that approach is mostly used for research purposes. 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.”
There is a long way to go before microbiome tests are used as an indicator of the evolution of patients’ gastrointestinal symptoms
Microbiome testing is still in its infancy. Here is a summary of some clinical takeaways that you can explain to your patients the next time they ask about the utility of microbiome tests:
- Scientists have not yet defined a healthy or normal gut microbiome that can reliably predict whether a person will develop a particular disease.
- Relying on stool samples for studying the gut microbiome is inaccurate as the microbiome in stool does not faithfully reflect the microbiome at the intestinal mucosa. The stool microbiome is stable over time and different from the luminal microbiome, which varies depending on each part of the gastrointestinal tract.
- Some commercial microbiome test reports describe the patient’s gut microbiome profile in terms of “good” and “bad” bacteria. The behavior of a particular gut microbe depends on the environment in which it lives and interactions with other commensal species. For instance, some people are asymptomatic colonizers of the potential pathogens Clostridioides difficile.
- That a commercial microbiome test provides a large amount of information is not an indicator of its reliability. Approximately 20% of bacterial gene sequences have not been identified and over 40% of the 10 million microbial genes have uncharacterized functions, which means the science on how to use diet or food supplements to correct specific levels of microbial metabolites is just not there yet.
- Currently, fecal microbiome analyses have limited value in guiding treatment decisions as they provide little important information on gastrointestinal symptom severity, which are ultimately the beacon that guide your clinical decisions.
Some potential applications of microbiome tests that are emerging but not ready to use as routine practice in the clinic as yet include the use of specific fecal microbial signatures to predict which patients will respond better to interventions.
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.
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.”
References:
Gacesa R, Kurilshikov A, Vich Vila A, et al. Environmental factors shaping the gut microbiome in a Dutch population. Nature. 2022; 604(7907):732-9. doi: 10.1038/s41586-022-04567-7.
Zhao L, Zhang F, Ding X, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018; 359(6380):1151-6. doi: 10.1126/science.aao5774.
Ma J, Li Z, Zhang W, et al. Comparison of gut microbiota in exclusively breast-fed and formula-fed babies: a study of 91 term infants. Sci Rep. 2020; 10(1):15792. doi: 10.1038/s41598-020-72635-x.
Hill C. You have the microbiome you deserve. Gut Microbiome. 2020; 1:E3. doi: 10.1017/gmb.2020.3.
Lagier JC, Khelaifia S, Tidjani Alou M, et al. Culture of previously uncultured members of the human gut microbiota by culturomics. Nat Microbiol. 2016; 1:16203. doi: 10.1038/nmicrobiol.2016.203.
Valdes AM, Walter J, Segal E, et al. Role of the gut microbiota in nutrition and health. BMJ. 2018; 361:k2179. doi: 10.1136/bmj.k2179.
Staley C, Kaiser T, Khoruts A. Clinician guide to microbiome testing. Dig Dis Sci. 2018; 63(12):3167-77. doi: 10.1007/s10620-018-5299-6.
Oh CJ, Rezaie A. Small is big: why the analysis of the fecal microbiome provides little important information on IBS severity. Dig Dis Sci. 2022. doi: 10.1007/s10620-022-07551-3.
Busquets D, Oliver L, Amoedo J, et al. RAID prediction: pilot study of fecal microbial signature with capacity to predict response to anti-TNF treatment. Inflamm Bowel Dis. 2021; 27(Suppl 2):S63-S66. doi: 10.1093/ibd/izab273.
Malagón M, Ramió-Pujo S, Serrano M, et al. New fecal bacterial signature for colorectal cancer screening reduces the fecal immunochemical test false-positive rate in a screening population. PLOS ONE. 2020; 15(12):e0243158.
