An approach to finding specific forms of dysbiosis that associate with different disorders

Abstract

Background: Many disorders display dysbiosis of the enteric microbiome, compared with healthy controls. Different disorders share a pattern of dysbiosis that may reflect "reverse causation", due to non-specific effects of illness-in-general. Combining a range of disorders into an "aggregate non- healthy active control" (ANHAC) group should highlight such non-specific dysbiosis. Differential dysbiosis between the ANHAC group and specific disorders may then reflect effects of treatment or bowel dysfunction, or may potentially be causal. Here, we illustrate this logic by testing if individual genera can differentiate an ANHAC group from two specific diagnostic groups. Methods: We constructed an ANAHC group (n=17) that had 14 different disorders. We then used random forest analyses to test differential dysbiosis between the ANHAC group and two other disorders that have no known pathology, but: (i) symptoms of illness (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome - ME/CFS - n = 38); or (ii) both illness and bowel dysfunction (ME/CFS comorbid with Irritable Bowel Syndrome - IBS - n=27). Results: Many genera differentiated the ANHAC group from co-morbid IBS. However, only two genera - Roseburia and Dialister - discriminated the ANHAC group from ME/CFS. Conclusions: Different disorders can associate with specific forms of dysbiosis, over-and-above non-specific effects of illness-in-general. Bowel dysfunction may contribute to dysbiosis in IBS via reverse causation. However, ME/CFS has symptoms of illness-in-general, but lacks known pathology or definitive treatment that could cause dysbiosis. Therefore, the specific dysbiosis in ME/CFS may be causal.