The study subjects were 50 patients with ME/CFS from four sites across the US (meeting 1994 CDC Fukuda and 2003 Canadian consensus criteria) and 50 healthy controls. Some of the ME/CFS patients (21/50) reported a diagnosis of irritable bowel syndrome, absent in all the controls. Whether IBS leads to ME/CFS or is a consequence is unclear.
Genomic DNA was extracted from a fecal sample from each patient and subjected to high-throughput sequencing. Bacterial sequences were identified after computational subtraction of human genomic, mitochondrial, and ribosomal sequences.
The results show that bacterial taxa in ME/CFS patients with and without IBS were distinct. The most reliable markers of ME/CFS with IBS were increased abundance of Alistipes (pictured) and a decrease in Faecalibacterium genera of bacteria. In contrast, an increase in Bacteriodes and a decrease in Bacteroides vulgatus were associated with ME/CFS without IBS.
The bacterial genes identified in the sequence analysis were used to predict alterations in metabolic pathways. Some pathways are altered only in ME/CFS patients, while others are linked to IBS. Enrichment in the pathway of vitamin B6 biosynthesis appeared to be independent of IBS. This vitamin plays a role in many aspects of metabolism, neurotransmitter synthesis, histamine synthesis, hemoglobin synthesis and function, and more, and is a cofactor for many essential reactions.
The unsaturated fatty acid biosynthesis pathway was also found to be reduced in ME/CFS patients independent of IBS. A reduction of specific fatty acids has been linked to pro-inflammatory responses and immune activation in ME/CFS patients.
These and other metabolic findings in ME/CFS patients validate additional work on bacterial metabolic pathways and the metabolome – the set of small-molecule chemicals – of ME/CFS patients.
Others have previously shown increased levels of cytokines in the plasma and cerebrospinal fluid of ME/CFS patients who had been ill for a short period of time. No such association was found in the current study, perhaps because most subjects had been ill for extended periods of time.
The dysbiosis and bacterial metabolic disturbances identified in this study of ME/CFS patients are intriguing. The results suggest that abundance of certain bacterial taxa could be used as diagnostic markers for the disease. The more important question is whether these changes are a cause or a consequence of ME/CFS. Answering this question is relevant to the potential for using microbiome transplants, or metabolic therapeutic strategies to ameliorate the disease.