Barrier Repair in ME/CFS: Lessons from Prototype Diseases

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is marked by heterogeneous symptom clusters and only partial or short-lived responses to interventions. While gut involvement has been implicated in ME/CFS, it has not been proven to be the root cause, nor have symptoms been consistently responsive to treatment.Methods: We analyze prototype illnesses with known gut barrier dysfunctions from the duodenum to the colon to identify similarities and symptoms that are direct results of barrier dysfunction. In particular, we assess what can be learned from these prototype diseases that depends not on pathogenesis, but on barrier breakdown and metabolite leakage.Results: Prototype diseases showed consistent involvement of pore pathways, frequent histamine leakage, and parallel treatment responses, despite differing in pathogenesis.