Ian Lipkin’s CII team shows gut bacteria in ME/CFS may influence disease severity

“Much like IBS, ME/CFS may involve a breakdown in the bidirectional communication between the brain and the gut mediated by bacteria, their metabolites, and the molecules they influence. By identifying the specific bacteria involved, we are one step closer to more accurate diagnosis and targeted therapies.” ~ Ian Lipkin, director of CII and John Snow Professor of Epidemiology at Columbia’s Mailman School.

 

Anticipated work from the CII teams’ early investigative research into ME/CFS is starting to be published. The new study in the journal Microbiome from Drs Ian Lipkin and Mady Horning at Columbia University Center for Infection and Immunity (CII) finds abnormal levels of certain types of bacteria in the gut microbiome of ME/CFS patients. It also found disturbances in bacterial metabolic pathways that, in combination with the changes in bacteria, may influence disease severity.

The CII team collaborated with some of the top clinicians in the field, including Klimas, Peterson, Montoya, Bateman and Levine, to ensure they had rigorously-diagnosed patients. Harvard Professor Tony Komaroff was part of the team too. The open access paper is titled ‘Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome’.

Researchers took fecal and blood samples from 50 patients and 50 healthy controls. They analysed cytokines in the blood, as they did in their original cytokine study and they applied metagenomics to the fecal samples. Metagenomics is a new field that combines remarkable technology for sequencing huge amounts of DNA with a kind of sophisticated genetic detective work to not only identify which bacteria are present, but also which bacterial metabolic pathways are active too. ME/CFS patients differed from controls in both.

Additionally, the authors state that their findings indicate that features unique to ME/CFS may be masked by disturbances arising from irritable bowel syndrome. They recommend that for more accurate results, microbiome studies should factor in whether or not ME/CFS patients have irritable bowel syndrome, IBS, which is very common among ME/CFS patients. This may help gain insight for the development of therapeutic strategies for both ME/CFS subgroups.

 

Some types of bacteria were strongly linked with ME/CFS cases whether or not they had IBS, while other bacteria were linked with those ME/CFS patients who also have IBS. This complex research paper is not easy reading, the research team analyzed a lot of data and highlighted many bacteria and metabolic pathways, but here are some interesting things:

  • Levels of distinct intestinal bacterial species—Faecalibacterium, Roseburia, Dorea, Coprococcus, Clostridium, Ruminococcus, Coprobacillus—were strongly associated with ME/CFS; their combined relative abundance appears to predict if someone has the illness.

 

  • Increased abundance of the Alistipes group of bacteria, and decreased Faecalibacterium were the top biomarkers of ME/CFS with IBS.

 

  • Enrichment in the pathway for vitamin B6 biosynthesis and salvage (i.e. recycling B6) was the strongest predictor of ME/CFS, regardless of whether or not patients had IBS. Vitamin B6 helps the body use and store both proteins and carbohydrate, as well as help form the haemoglobin that carries oxygen round the body. There is some evidence B6 is low in patients, but this could be down to changes in the body rather than in gut bacteria.

 

  • No changes were observed in immune markers which may reflect the lack of participants who had been ill for a short time; earlier research suggests immune changes may only be evident when comparing short and long duration cases

 

Bacterial types and metabolic data combined correlate with symptom severity

An intriguing finding was from analysis that combined data on changes in metabolic pathways with data on bacterial types. In ME/CFS subgroups, symptom severity measures, including pain and fatigue, correlated with the abundance of distinct bacterial types and metabolic pathways.

“Individuals with ME/CFS have a distinct mix of gut bacteria and related metabolic disturbances that may influence the severity of their disease,” says co-lead investigator Dorottya Nagy-Szakal, postdoctoral research scientist at CII.

 

It is important to note that it is not clear if dysbiosis is contributing to metabolism changes. The researchers state “more work is needed to assess the relationship between the bacterial metabolic pathways identified by using gene content, bacterial metatranscriptomics, and metabolome in ME/CFS” and they concluded with:

“Our results confirm and extend previous work indicating intestinal dysbiosis in ME/CFS. We further demonstrate that patterns of dysbiosis vary with IBS co-morbidity. Future prospective studies should consider more detailed exploration of IBS subtypes, associated GI symptoms, and their relationship to ME/CFS dysbiosis. The identification of ME/CFS networks—characterized by specific profiles that integrate microbiota, metabolic pathways, and plasma immune molecules—may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies.”

 

Cort Johnson has done serious homework on this latest research and more in a blog on the Simmaron Research website which is well worth reading.

Our MDP team is looking forward to the CII teams’ early investigative work in ME/CFS using proteomics and metabolomics – yet to be published. You can see some information on their program of research into ME/CFS on our homepage.

Imagine what this team could achieve with the huge study combining multiple areas of research on 125 patients and 125 controls with multiple sample types at 4 time points using a systems-biology approach. The Columbia CII team needs donations for this work please read about this brilliant study and consider making a donation.