Your top clinical questions answered
As gut microbiome experts, the Co-Biome team have answered some of the most common MetaXplore questions from our healthcare professionals.
Clinical FAQs
Accurate assessment of methane production is valuable so you can confidently manage transit time. This means looking beyond the most widely recognised methane producer Methanobrevibacter smithii and understanding the potential of the entire microbial ecosystem to produce methane, including species such as Methanobrevibacter_A_smithii, Methanosphaera stadtmanae, and Methanomassiliicoccales_A intestinalis.
MetaXplore can provide more accurate reporting of methane production potential from all species within the gut microbiome.
Clinical consideration: By only looking for one species known to produce methane, you are not gaining a complete picture of the potential of methane production within your patient’s gut microbiome. Instead, use MetaXplore to gain a full understanding of methane producing archaea and use the Species Explorer to find methane producing species and their relative abundance.
The metagenomic technology used in MetaXplore™ can assess the presence of over 28,000 species, this includes seven species from the genus Candida (and many other species of yeasts and fungi).
Published metagenomic studies and our own in-house data have found that in general, the overall contribution of eukaryotes to the gut microbiome in healthy people is less than 0.1%1 and that of fungi is 0.01% or less2,3. The limit of detection for the metagenomic MetaXplore test is 0.01% relative abundance, thus for most people, fungal species such as Candida, will fall below this level. Clinically relevant levels of fungal species, when assessed as part of the entire gut microbiome, have not yet been developed. However, in general, individuals with fungal overgrowths will have higher levels than 0.01% relative abundance.
1. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010; 464(7285):59-65. doi:10.1038/nature08821
2. Xie Z, Manichanh C. FunOMIC: Pipeline with built-in fungal taxonomic and functional databases for human mycobiome profiling. Comput Struct Biotechnol J. 2022; 20:3685-3694. doi:10.1016/j.csbj.2022.07.010
3. Nash AK, Auchtung TA, Wong MC, et al. The gut mycobiome of the Human Microbiome Project healthy cohort. Microbiome. 2017;5(1):153. Published 2017 Nov 25. doi:10.1186/s40168-017-0373-4
Clinical consideration: While MetaXplore metagenomic analysis can detect fungal species such as Candida albicans, it is rare for it to be reported. It is important to note that Candida is only present at very low levels in healthy people, so even if detected at even lower levels with more sensitive methods, it is unlikely to be clinically relevant at such low levels.
The pathogenic role of Dientamoeba fragilis and Blastocystis hominis subtypes has not been established. These protists are often observed at similar or higher levels in asymptomatic controls than individuals with gastrointestinal symptoms1,2, indicating they are likely not causal of GI symptoms. Some studies have even observed higher microbial diversity in individuals with Blastocystis3.
Most cases do not require antimicrobial treatment, and this will often not clear the protozoa but may disrupt the normal gut microbiome. If symptomatic, other causes should be excluded (e.g. other infections, irritable bowel syndrome, food intolerances). Screening for clearance of the organism or testing of family members is not recommended.
1. de Boer MD, Schuurs TA, Vermeer M, et al. Distribution and relevance of Dientamoeba fragilis and Blastocystis species in gastroenteritis: results from a case-control study. Eur J Clin Microbiol Infect Dis. 2020;39(1):197-203. doi:10.1007/s10096-019-03710-z
2. Shasha D, Grupel D, Treigerman O, et al. The clinical significance of Dientamoeba fragilis and Blastocystis in human stool-retrospective cohort study. Clin Microbiol Infect. 2024;30(1):130-136. doi:10.1016/j.cmi.2023.09.003
3. Stensvold CR, Sørland BA, Berg RPKD, et al. Stool Microbiota Diversity Analysis of Blastocystis-Positive and Blastocystis-Negative Individuals. Microorganisms. 2022;10(2):326.
Clinical consideration: Focus on a healthy balance within the whole gut microbiome. MetaXplore provides both clinical and research insights that can help support your patients towards a more robust microbiome by focusing on increasing microbial diversity and the growth of beneficial gut species using science-backed diet and prebiotic interventions.
High levels of oral species in the gut microbiome may indicate an imbalance in the microbial community. Studies have shown they can promote gut inflammation and are increased in several disease states1.
Previously it was thought that oral bacteria only reached and colonised the gut under specific circumstances such as when there is low gastric acidity (often due to the use of proton pump inhibitor (PPI) medications), during antibiotic use (reduces native gut microbes and favours colonisation of oral bacteria), or if the oral bacterial species are acid resistant (e.g. Streptococcus mutans, Porphyromonas gingivalis)1. However, now studies have shown that low levels of microbes from the mouth regularly make it to the gut (even in healthy people), and colonisation levels are higher in individuals with disease (in addition to individuals that use PPIs/antibiotics)2. Studies have also indicated oral bacteria in the gut can trigger inflammation3. Thus, assessing the levels of oral species present in the gut microbiome can be another indicator of gut microbiome health.
1. Kunath BJ, De Rudder C, Laczny CC, Letellier E, Wilmes P. The oral-gut microbiome axis in health and disease. Nat Rev Microbiol. 2024; doi:10.1038/s41579-024-01075-5
2. Schmidt TS, Hayward MR, Coelho LP, et al. Extensive transmission of microbes along the gastrointestinal tract. Elife. 2019;8:e42693. doi:10.7554/eLife.42693
3. Kitamoto S, Nagao-Kitamoto H, Jiao Y, et al. The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis. Cell. 2020;182(2):447-462.e14. doi:10.1016/j.cell.2020.05.048
Clinical consideration: The levels of oral species in the gut can be an indicator of microbiome health. Use MetaXplore to determine the presence of oral species in your patient’s gut microbiome.
These two measures of SCFAs will answer different questions. By measuring the overall capacity of the gut microbiome to produce SCFAs, you can answer the question of “How does the ability to produce SCFAs in my patient compare to healthy people?”
By measuring the amount of faecal SCFAs, you can answer the question of “What amount of SCFAs are left over after absorption by intestinal cells?” It is important to note that faecal SCFA levels do not reflect the rate of SCFA production or absorption by the gut microbiome1. This is because most SCFAs are quickly absorbed by intestinal cells as soon as they are produced, and absorption rates differ by individual2. This makes measures of faecal SCFAs difficult to interpret without additional information. For example, a high faecal level of SCFAs could indicate high SCFA production and an average rate of intestinal absorption (not a concern), or it could also indicate average/low SCFA production, and a low rate of intestinal absorption (a concern).
1. Sakata T. Pitfalls in short-chain fatty acid research: A methodological review. Anim Sci J. 2019; 90: 3–13.
2. Stumpff F. A look at the smelly side of physiology: transport of short chain fatty acids. Pflugers Arch. 2018;470(4):571-598. doi:10.1007/s00424-017-2105-9
Clinical consideration: Measuring the overall capacity of the gut microbiome to produce SCFAs provides an easy to interpret measure of the microbiome’s ability to produce SCFAs and is not confounded by an individual’s rate of SCFA absorption.
The presence of Gram-negative bacteria is not necessarily indicative of an inflammatory state, as this category also includes commensals. Over-reliance on the G+/G− ratio could lead to misdiagnosis or inappropriate treatment.
An inflammatory response depends on the structure of lipopolysaccharides (LPS), which are components of Gram-negative bacterial cell walls1. MetaXplore measures the number of microbial cells with the genetic capacity to produce hexa-LPS, the specific structure of LPS found in Gammaproteobacteria, that triggers inflammation1. Most other Gram-negative bacteria produce under-acylated LPS, which cannot trigger inflammation and may actually play a beneficial role by inhibiting inflammatory signaling2.
MetaXplore also assesses the body’s potential response to hexa-LPS by factors such as the integrity of the gut barrier and presence of anti-inflammatory mechanisms.
1. Di Lorenzo, F., De Castro, C., Silipo, A. & Molinaro,A. Lipopolysaccharide structures of gram-negative populations in the gutmicrobiota and effects on host interactions. FEMS Microbiol Reviews. 2019;257-272.Doi: 10.1093/femsre/fuz002
2. d'Hennezel E, Abubucker S, Murphy LO, Cullen TW. Total Lipopolysaccharide fromthe Human Gut Microbiome Silences Toll-Like Receptor Signaling. mSystems.2017;2(6):e00046-17. doi:10.1128/mSystems.00046-17
Clinical consideration: Don’t risk being misguided by using the gram-positive/gram-negative ratio to indicate inflammation. Instead, use MetaXplore to measure the hexa-LPS production potential, the specific structure of LPS found in Gammaproteobacteria, that triggers inflammation1. MetaXplore also considers the health of the entire gut microbiome by assessing the body’s potential response to LPS through evaluation of gut barrier integrity and the presence of anti-inflammatory mechanisms.
Not necessarily. Every patient will have a unique gut microbiome and there are many different microbial communities that are deemed healthy. We can learn more about the gut microbiome by looking at the function of the whole community rather than just a few well-known celebrity species. Instead of focusing on a few well-known species, you can look at promoting overall microbial diversity, as diverse microbiomes can help prevent the overgrowth of pathogens and pathobionts1,2.
1. Leshem A, Liwinski T, Elinav E. Immune-Microbiota Interplay and Colonization Resistance in Infection. Mol Cell. 2020;78(4):597-613. doi:10.1016/j.molcel.2020.03.001
2. Fassarella M, Blaak EE, Penders J, et al. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health. Gut 2021;70:595-605.
Clinical consideration: Rather than search through a MetaXplore report looking for well-known celebrity species, it is important to look at the function of the whole gut microbiome community by assessing microbial markers and diversity. There may be other, less known species in the individual’s microbiome that are performing the same function.
The Firmicutes to Bacteroidetes (F/B ratio) is a simplistic measure of two common bacterial phyla in the gut and historically was suggested as being associated with body mass index. However, later studies demonstrated the F/B ratio does not hold up when assessed across more datasets and larger sample sizes1,2. Science now knows that there are many beneficial and detrimental microbes present in both phyla, and so looking at the phylum level doesn’t provide enough accuracy to understand what’s really going on in your gut.
For this reason, you will not find a F/B ratio calculation in MetaXplore reports, however you will find reporting on the Firmicutes and Bacteroidetes phyla. This information is available in the species table in our reports (note that Firmicutes has been divided into several phyla “_A, _B, _C,” etc. based on genetic differences).
MetaXplore measures the composition of the microbiome at the species level. This is the resolution needed to unravel how the different organisms in your gut contribute to health. Even more important is understanding the beneficial or detrimental functions those microbes can perform, which can be found in our reports.
1. Finucane MM, Sharpton TJ, Laurent TJ, Pollard KS. A Taxonomic Signature of Obesity in the Microbiome? Getting to the Guts of the Matter. Heimesaat MM, ed. PLoS ONE. 2014;9(1):e84689. doi:https://doi.org/10.1371/journal.pone.0084689
2. Walters WA, Xu Z, Knight R. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Letters. 2014;588(22):4223-4233. doi:https://doi.org/10.1016/j.febslet.2014.09.039
Clinical consideration: Instead of reporting on the Firmicutes/Bacteroidetes ratio that doesn’t provide enough accuracy into what is happening in the gut, MetaXplore measures the composition of the microbiome at the species level. This is needed to understand the different organisms in your patient’s gut and how they are performing beneficial or detrimental functions that can impact their health. You can use the MetaXplore Species Explorer to find out more about health associations and functions of different species within the phyla.
We understand there is a common belief that antimicrobial herbs are needed to change the composition of the gut microbiome. However, this is based on outdated findings where the whole microbiome has not been assessed. As gut microbiome guardians, you will find only one antimicrobial herb out of over 70 diet, lifestyle and supplement recommendations featured in MetaXplore. This is because we understand non-specific antimicrobial herbs can impact both detrimental and commensal species and may promote dysbiosis instead of re-balance.
Clinical consideration: Rather than defaulting to antimicrobial herbs for gastrointestinal symptoms, test the whole gut microbiome using MetaXplore and get answers on markers of gastrointestinal health, gut terrain and dysbiosis. You can then utilise the diet, lifestyle and supplement insights for personalised patient management.
Everyone’s microbiome is unique and there are many different healthy microbial communities. It is important not to focus on a few well-studied probiotic bacterial species, but to instead focus on the microbial community as a whole.
When assessing the entire microbial community with metagenomic technology used in MetaXplore, the presence of probiotic species is typically rare and if present, are at very low amounts relative to the rest of the microbial community. This is because many probiotic strains are not native colonisers of the adult human gut and are only present for a short period of time after ingestion (probiotic strains are often derived from the infant gut or from fermented foods)1.
Research also tells us that the microbiomes of healthy people typically have a good diversity of anaerobic, fibre-degrading species that produce beneficial short-chain fatty acids such as butyrate, propionate and acetate2-4.
1. Walter J. Ecological Role of Lactobacilli in the Gastrointestinal Tract: Implications for Fundamental and Biomedical Research. Applied and Environmental Microbiology. 2008;74(16):4985-4996. doi:https://doi.org/10.1128/aem.00753-08
2. van der Hee B, Wells JM. Microbial Regulation of Host Physiology by Short-chain Fatty Acids. Trends Microbiol. 2021;29(8):700-712. doi:10.1016/j.tim.2021.02.001
3. Blaak EE, Canfora EE, Theis S, et al. Short chain fatty acids in human gut and metabolic health. Benef Microbes. 2020;11(5):411-455. doi:10.3920/BM2020.0057
4. Fassarella M, Blaak EE, Penders J, et al. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health. Gut 2021;70:595-605.
Clinical consideration: Rather than search through a MetaXplore report looking for probiotic species, it may be better to look at the overall diversity of the microbiome and its capacity to produce beneficial short-chain fatty acids such as butyrate, propionate and acetate.