Groundbreaking research led by a physician-scientist and pain management specialist at Rambam Healthcare Campus (Rambam) in Haifa, Israel, reveals how the microbiome can alleviate some symptoms associated with fibromyalgia.
Dr. Amir Minerbi. Photography: Rambam HCC
Dr. Amir Minerbi, MD/PhD, deputy director of the Institute for Pain Medicine at Rambam, member of the Clinical Research Institute at Rambam, and a senior lecturer at the Technion – Ruth and Bruce Rappaport Faculty of Medicine led a groundbreaking study of the effects of gut bacteria (microbiomes) transplanted from healthy individuals to female patients with severe fibromyalgia. The research was conducted in collaboration with colleagues from McGill University in Canada, Professors Yoram Shir and Arkady Khotorsky, and physician-scientist, Dr. Milena Pitashny, head of the Clinical and Research Microbiome Center at Rambam.
Fibromyalgia is a disorder affecting 2%–4% of the population and is more common in women. It is characterized by widespread and persistent pain, fatigue, and concentration and memory-related issues.
In this study, conducted by MA student Rana Haddad, fifteen Rambam patients grappling with treatment-resistant severe fibromyalgia participated in this novel study. The microbiomes of healthy research subjects were given to fibromyalgia patients via an ingestible capsule. Eleven study participants reported less pain, fatigue, and memory disturbances, surpassing the effects of prior treatments. This improvement continued for months, and the patients returned to work, studies, and their usual lifestyles.
“Because of its elusive nature, fibromyalgia is categorized as a disorder rather than a disease,” explains Dr. Minerbi. “There are many symptoms, but its cause is unclear.
Currently, there is no method for diagnosis other than the subjective reports of patients.” According to Minerbi, the medical establishment has neglected the disorder, and female patients often encounter skepticism from their healthcare providers. “The underlying cause of the symptoms remains unknown and this hinders development of specific treatments. We rely on pain management and treatment of the fatigue and memory loss; however, these are all palliative and ineffective.” Minerbi points out that despite the best available treatments, most patients will continue to suffer from severe symptoms and a significant impairment in their quality of life. The pilot study was funded by the Weston Family Foundation and Israel Ministry of Health.
Finding the microbiome-fibromyalgia connection
Dr. Minerbi’s study of the link between gut bacteria and fibromyalgia began in 2017 when he was working on his postdoctoral fellowship at McGill University under the supervision of Prof. Yoram Shir. He and his colleagues wanted to find out if the gut microbiota could also influence pain processes. They focused on pain in fibromyalgia for several reasons: the unknown cause, its prevalence, and the lack of an effective diagnostic or treatment method.
The initial research phase, conducted in collaboration with McGill bioinformatics expert Dr. Emanuel Gonzalez and with Dr. Nicholas Brereton from the University of Montreal, examined the statistical differences in microbiome composition between healthy individuals and those with fibromyalgia. Indeed, they found marked differences between 20 bacterial species that varied in prevalence between the two groups, and the greater the differences in the fibromyalgia group, the more severe their symptoms.
Further analysis showed that these bacteria released certain substances linked to the nervous system and the severity of pain reported by the patients. Minerbi explains the importance of this finding: “We found an almost direct connection between the concentration of specific substances influenced by bacterial activity and the intensity of reported pain by the patients. Importantly, these substances can be measured in the blood! This finding may enable the development of blood tests for diagnosing and monitoring fibromyalgia.”
Now the team had to establish causality, i.e., did these specific microbiomes cause fibromyalgia? This question was addressed in collaboration with Prof. Arkady Khoutorsky’s lab at McGill. The research scientists transplanted microbiomes from healthy female patients into bacteria-free mice. Within two weeks, the mice exhibited symptoms of fibromyalgia that persisted for months, providing compelling evidence of the microbiome’s role in the development of fibromyalgia. Further investigation revealed an impact on the immune system, disrupting its balance and causing it to target areas of the nervous system responsible for pain sensation. The mice were given antibiotics to treat the diseased microbiome, after which, microbiomes from healthy women were transplanted into the mice. Remarkably, pain symptoms in the mice quickly disappeared.
What lays ahead?
Recently, Minerbi and colleagues uploaded their initial findings to a pre-peer review website, and a manuscript submitted for publication in a prominent medical journal.
The initial success of the study has encouraged the research team to prepare a more comprehensive investigation. “The study lacked a control group and randomization. Soon, we will recruit 80 patients for a larger, controlled trial, which we expect to confirm our findings,” Dr. Minerbi adds.
Dr. Minerbi is excited by the dramatic results of this groundbreaking research, which opens the way for further understanding and possible diagnostic and treatment breakthroughs for people suffering from fibromyalgia.
Based on an article that first appeared on the YNet Hebrew lifestyle website.