September 23, 2022

expert reaction to study linking higher levels of antibodies against Lachnospiraceae bacteria in people with CFS/ME

A study published in Science Advances looks at antibody responses against human microbiota flagellins in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients.

Prof Eleanor Riley, Professor Emerita, Immunology and Infectious Disease, University of Edinburgh, said:

“This study brings together two potential explanations for the underlying pathology of ME/CFS, namely a disturbance in the normal bacterial flora of the gut and a disturbance in the immune system, by looking at antibody responses to bacteria that are normally present in the gut. The methods used allowed the researchers to look for antibodies to a very large array of different organisms – and to different components of these organisms – and found some statistically significant differences in the prevalence of antibodies to some bacterial components between healthy people and people with severe ME/CFS. The authors conclude that the study provides additional evidence in favour of disturbances in the gut bacteria as a potential cause of some ME/CFS symptoms but are wisely very cautious in their interpretations.

“This caution is welcome as the study suffers from many of the limitations of recent ME/CFS research including being small in scale (only 40 patients and 40 healthy controls were tested), comparing patients only with healthy controls rather than with people with other fatiguing conditions (which would control for many of the lifestyle factors that may affect the results) and looking at only one time point in the evolution of their illness (which makes it impossible to determine whether the differences seen are causes or consequences of the disease). 

“It is a sad truth that results from the vast majority of these small studies of ME/CFS fail to be confirmed in subsequent studies. This study should therefore be viewed as hypothesis generating, providing interesting new avenues for future research, rather than as being in any way conclusive.”

Prof Alan Carson, Professor of Neuropsychiatry, University of Edinburgh, said:

“The findings of a potential link between gut microbiome add to a growing literature on such links across a range of neurological and psychiatric disorders. Abnormalities in the immune system have been established in CFS/ME since 1980s but interpretation of what they actually mean is hampered by uncertainty of whether they are cause or effect- activity levels alone will impact, or whether it might link to the confounding effects of depressive or anxiety disorders which have long been linked with similar changes.

“This study adds incrementally to such knowledge but is of only modest interest as the patient phenotype from this biobank is not well characterized, so it is not clear what is actually wrong with the patients and within the study itself it is not clear how the 40 blood samples used were chosen from the several hundred in the biobank. The size of the effect found is quite small so chance findings cannot be ruled out. The necessary first step is for replication by an independent group from a separate sample. It’s a long way from knowing if this is indeed a biomarker specific to ME/CFS.”

‘Systemic antibody responses against human microbiota flagellins are overrepresented in chronic fatigue syndrome patients’ by Thomas Vogl et al. was published in Science Advances at 19:00 UK TIME Friday 23 September 2022.

DOI: 10.1126/sciadv.abq2422

Declared interests

Prof Alan Carson: “I chaired the writing group for the Scottish good practice statement on CFS/ ME. I am an unpaid president of the functional neurologic disorder society. Paid editor of the Journal of neurology neurosurgery and psychiatry and I give independent testimony in court on a range of neuropsychiatry topics, I have no financial or other interests that could be affected by this study.”

Prof Eleanor Riley: Researcher and grant holder (from 2013 to 2018) at the UK ME/CFS Biobank at the London School of Hygiene and Tropical Medicine that provided the samples for this study. She had no involvement in any aspect of this study.