High levels of antibodies against specific gut bacteria may be linked to chronic fatigue

The findings of a new research suggest that combining Lachnospiraceae antibody screening with blood tests could improve the diagnosis of ME/CFS.
Table of Contents

What is already known
People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience prolonged, extreme exhaustion as well as other symptoms including mental clouding, muscle pain and gut problems. Although the triggers of ME/CFS are unclear, some studies have suggested that imbalances in immune responses and the gut microbiota may play a role. However, how the immune system and gut microbes interact remains poorly understood.

What this research adds
Researchers analyzed the antibody responses of 40 people with severe ME/CFS and 40 healthy controls against a database of more than 200,000 microbiota and viral antigens. Compared with healthy people, those with ME/CFS had higher levels of antibodies that target Lachnospiraceae bacteria. Combining conventional blood tests with antibody screening improved by 25% the diagnosis of ME/CFS compared with blood tests alone.

Conclusions
The findings provide additional evidence of a link between gut bacteria and ME/CFS. They also suggest that combining Lachnospiraceae antibody screening with blood tests could improve the diagnosis of ME/CFS.

Chronic fatigue syndrome, also known as myalgic encephalomyelitis, is a debilitating disease whose triggers are unknown and for which there are no standard diagnostic tools. Now, a small study suggests that people with chronic fatigue tend to have high levels of antibodies against a specific type of gut bacteria.

The findings, published in Science Advances, suggest that combining antibody screening with blood tests could improve the diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

People with ME/CFS experience prolonged, extreme exhaustion as well as other symptoms including mental clouding, muscle pain and gut problems. Although the triggers of the condition are unclear, some studies have suggested that imbalances in immune responses and the gut microbiota may play a role. However, how the immune system and gut microbes interact remains poorly understood.

A team of researchers led by Thomas Vogl and Eran Segal at the Weizmann Institute of Science set out to investigate the link between immune responses and gut microbes in 40 people with ME/CFS.

Antibody response

The researchers collected blood from 40 people with severe ME/CFS and 40 healthy controls. Then, they analyzed the antibody responses of each person against a database of 244,000 microbiota and viral antigens.

Compared with healthy people, those with ME/CFS had higher levels of antibodies that target flagellins of Lachnospiraceae bacteria, which include species such as Roseburia inulinivornas and Roseburia faeci

Flagellins are structural proteins of the flagellum, a surface filament dedicated to bacterial motility, and a similar overrepresentation of antibodies against Lachnospiraceae flagellins has been reported in Crohn’s disease, a type of inflammatory bowel disease.

Disease biomarker

Next, the team used machine learning to assess whether screening for antibodies against Lachnospiraceae could be used together with blood tests that are typically used to diagnose ME/CFS.

Combining conventional blood tests with antibody screening improved by 25% the diagnosis of ME/CFS compared with blood tests alone, the researchers found.

“Elevated Lachnospiraceae abundances have not explicitly been reported in gut microbiome sequencing of patients with severe ME/CFS, … pointing toward a peculiar role of anti-Lachnospiraceae [antibody] responses,” the researchers say. 

Although stool samples or metagenomic data are unavailable for the individuals analyzed in this study, the findings provide additional evidence of a link between gut bacteria and ME/CFS, the authors say.