As research into the human micro- and myco-biome continues to expand, scientists have uncovered several correlations between various disease states and the prevalence/abundance of certain yeasts, bacteria, and fungi. Many difficult-to-diagnose conditions correlate with changes in gut flora, which may offer a potential route for diagnosis or perhaps even prevention.

Fibromyalgia has presented a diagnostic challenge for many years now.^1-2 Yet it is one of the most common kinds of widespread chronic pain, affecting an estimated 2-8% of the population.³ For primary care clinicians, treatment challenges remain, as fibromyalgia is a chronic illness persisting across the lifespan.⁴ Researchers suggest that many cases of fibromyalgia are undiagnosed, in part because of the difficulty in obtaining a definitive diagnosis.⁵

A new Canadian study offers hope for accurate, rapid diagnosis through analysis of the microbiome.⁶ In the study, two female cohorts were examined: one with fibromyalgia (n=77) and one without (n=79). Family members and others cohabitating with the patients with fibromyalgia were also included to reduce variability due to environmental factors, as well as unrelated controls (48 of the 79). Stool samples were subjected to genomic analysis, and substantial, significant differences were found between individuals with and without fibromyalgia. This was despite the overall microbial population and diversity being relatively similar across the two groups. Diet quality, caloric intake, and vitamin, mineral, sugar, and fatty acids intake did not differ between groups.⁶

Fibromyalgia disease severity correlated with prevalence of certain taxa in the microbiome.⁶ Notably, the fibromyalgia cohort had lower levels of Faecalibacterium prausnitzii (butyrate-producing), Bacteroides uniformis (butyrate-producing), Prevotella copri, and Blautia faecis, as well as higher levels of these butyrate producers:

• Intestinimonas butyriciproducens
• Flavonifractor plautii
• Butyricoccus desmolans
• Eisenbergiella tayi
• Eisenbergiella massiliensis

Serum levels of both butyrate and propionate also differed between the two cohorts. Two microbes responsible for conversion of cortisol to androgens were elevated in the fibromyalgia cohort: Clostridium scindens and B. desmolans.⁶

When these populations were compared to previous studies in patients with chronic fatigue syndrome (CFS), there was some overlap, but there were also distinct differences between groups of patients with each diagnosis; for instance, P. merde was elevated in fibromyalgia but depleted in CFS.⁶ Distinct microbial signatures have also been found predictive of or correlated with other diagnoses, including colorectal cancer,⁷ non-alcoholic fatty liver disease,^8-9 and many more.

This study offers potential for developing microbial signatures of fibromyalgia, enabling diagnosis, particularly when paired with existing standards for fibromyalgia diagnosis. However, the study had 90% Caucasian participants, so testing the hypothesis in other populations is still necessary. Techniques to restore the microbiome could potentially offer an avenue for treatment, once the causality has been determined.

As Joël Doré, director of research at the French National Institute for Agricultural Research and scientific director of MetaGenoPolis, a unit of the Micalis Institute “Food and Gut Microbiology for Human Health,” stated in an interview:

Microbiome signatures may be far more discriminant in their predictive value than any single or even combination of human genetic markers.”¹⁰

That said, microbiome research is ongoing. At this time, accurate diagnosis of complex gut flora for signatures of chronic illnesses is not clinically available.¹¹ The promise, however, continues to grow.

References

1. Borchers AT, Gershwin ME. Fibromyalgia: a critical and comprehensive review. Clin Rev Allergy Immunol. 2015;49(2):100-151. doi:1007/s12016-015-8509-4
2. Ghavidel-Parsa B, Bidari A, Hajiabbasi A, Shenavar I, Ghalehbaghi B, Sanaei O. Fibromyalgia diagnostic model derived from combination of American College of Rheumatology 1990 and 2011 criteria. Korean J Pain. 2019;32(2):120-128. doi:3344/kjp.2019.32.2.120
3. Clauw DJ. Fibromyalgia: a clinical review. 2014;311(15):1547-1555. doi:10.1001/jama.2014.3266
4. Clauw DJ, D’Arcy Y, Gebke K, Semel D, Pauer L, Jones KD. Normalizing fibromyalgia as a chronic illness. Postgrad Med. 2018;130(1):9-18. doi:1080/00325481.2018.1411743
5. Arnold LM, Gebke KB, Choy EH. Fibromyalgia: management strategies for primary care providers. Int J Clin Pract. 2016;70(2):99-112. doi:1111/ijcp.12757
6. Minerbi A, Gonzalez E, Brereton NJB, et al. Altered microbiome composition in individuals with fibromyalgia.Published online June 18, 2019. doi:10.1097/j.pain.0000000000001640
7. Yachida S, Mizutani S, Shiroma H, et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat Med. 2019;25(6):968-976. doi:1038/s41591-019-0458-7
8. Loomba R, Seguritan V, Li W, et al. Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease. Cell Metab. 2017;25(5):1054-1062.e5. doi:1016/j.cmet.2017.04.001
9. Caussy C, Tripathi A, Humphrey G, et al. A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease. Nat Commun. 2019;10(1):1406. doi:1038/s41467-019-09455-9
10. Versalovic J, Dore J, Guarner F, Luna RA, Ringel Y. Microbiome-based diagnostics: ready for applications in laboratory medicine? Clin Chem. 2017;63(11):1674-1679. doi:1373/clinchem.2016.264473
11. Cani PD. Human gut microbiome: hopes, threats and promises. 2018;67(9):1716-1725. doi:10.1136/gutjnl-2018-316723