Potential Targets for ME/CFS Clinical Trials
This week showcased Bateman Horne Center’s strategic plan in action. The new research published in two separate papers in the prestigious journal, Cell Host & Microbe, provided further evidence that the microbiome and metabolome contribute to the pathology of ME/CFS. Both papers reveal significant differences in the microbiome diversity, abundance, and functional biological pathways of research participants with ME/CFS compared to healthy controls. They validate similar findings from previous studies, identify potential biomarkers, and point toward a path for ME/CFS treatment trials.
BHC served as the Clinical Core for The Jackson Laboratory ME/CFS Collaborative Research Center (JAX) that published the paper titled, “Multi-‘omics of host-microbiome interactions in short- and long-term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).” A unique and important aspect of this study was the inclusion of ME/CFS patients with short-duration illness. Dr. Lucinda Bateman saw “new onset” patients as one of the biggest gaps in ME/CFS research and designed the study to compare short-duration ME/CFS patients to ME/CFS patients sick for a long time. We brought patients into the clinic who had experienced ME/CFS symptoms for no more than 3 years (this was 2017 so they had to have become ill in 2014 or later). Medical records were obtained for all patients and reviewed. If they met strict eligibility criteria, they were invited to participate in this 4-year study. Our initial aim was to enroll 150 ME/CFS patients that had been sick for <3 years but after a year of (really hard work) reviewing medical histories and clinical characterization, we realized it was important to compare short-duration ME/CFS patients to long-duration ME/CFS patients. As you will read below, this was a fortuitous change of course.
As Clinical Core, we were responsible for identifying, screening, enrolling, collecting blood and stool samples and comprehensive medical history and clinical data on 150 ME/CFS patients (75 short-duration ME/CFS patients and 75 long-duration ME/CFS patients) and 90 healthy controls. All ME/CFS patients were followed for up to 4 years with blood and stool and surveys collected each year. The JAX CRC results compare ME/CFS patients and controls from year 1 of the study. So there are many more exciting results to come! At a high level, this paper found that short-duration illness ME/CFS patients had more microbial imbalance or dysbiosis in the gut, while longer-duration ME/CFS patients’ gut microbiome was more like healthy controls. However, the longer duration ME/CFS patients had more severe disease presentation including pain and sleep problems and metabolic abnormalities. Finding that short-duration ME/CFS patients have different ongoing pathophysiology compared to long-duration ME/CFS patients is very important as it highlights targeting treatment to the appropriate ME/CFS group. For example, a dietary or probiotic intervention may be more appropriate for short-duration ME/CFS patients whereas long-duration illness ME/CFS patients may benefit from treatment(s) that target metabolomic disturbances.
BHC was also one of the five clinical sites involved in the study described in, “Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS.” The laboratory team at the Center for ME/CFS Solutions analyzed stool samples from 106 ME/CFS cases and 91 health controls. The metagenomic and metabolic analyses findings indicate that gut bacteria Faecalibacterium prausnitzii and Eubacterium rectale, which are both normally abundant and health-promoting, were reduced in ME/CFS participants. Loss of these important bacteria in individuals with ME/CFS contributed to deficient microbial capacity for synthesizing butyrate, a multifunctional bacterial metabolite with anti-inflammatory properties and the main fuel for the body’s colon cells. The abundance of Faecalibacterium prausnitzii was inversely associated with fatigue severity in ME/CFS, providing a direct link between the microbiome and disease symptoms.
FDA-approved treatments for ME/CFS are urgently needed and BHC’s strategic goal is to engage patients to participate in clinical research that accelerates ME/CFS clinical trials. The success of the research described in these two landmark studies is due in large part to the heroic participation of ME/CFS patients. The results generated from these two NIH-funded collaborative research centers provide solid evidence for promising targets that will be pursued in ME/CFS clinical trials.
This research was funded by the National Institutes of Health (NIH) with grants to the Center for Solutions for ME/CFS at Columbia University (grant number 1U54A138370) and The Jackson Laboratory (grant number 1U54NS105539).
Read the NIH press release about the studies here.
Read the BHC press release about the studies here.
Read the JAX research highlight here.