Gastrointestinal (GI) dysbiosis has been described as an imbalance in the gut microbial community that may be associated with disease. However it is clear that varied dysbioses are diet-driven, and may not be associated with current overt symptoms or pathologies. Disease specific dysbioses have yet to be definitively identified in the research setting, but a validated PCR-based test for accurate identification and characterization of dysbiosis is available to clinicians.
A eubiotic or normobiotic bacterial community cooperatively maintains microbial and host defense and anti-inflammatory systems. Those systems facilitate tolerance of common intrusions by opportunistic and exogenous pathogens. The intruders benefit from dysbiosis, and the host’s defensive inflammatory response- which can exacerbate dysbiosis. GI inflammation is commonly associated with a degree of secretory diarrhea that can alter the nutritional state of the microenvironment, and the abundance and diversity of the commensal flora. Inflammation is also associated with generation of nitrate, S-oxides and N-oxides. Those compounds provide a competitive growth advantage for potentially pathogenic bacteria, such as species within the Proteobacteria phyla (Enterobacteriaceae family). It is often not clear whether dysbiosis is a cause or an effect of infection or inflammation, but accurate identification and characterization of dysbiosis is important toward appropriate clinical intervention.
Normobiosis is characterized by an abundance of diverse, yet functionally redundant bacterial guilds rather than the presence of just a few “rock star” species. Potentially pathogenic species (Proteobacteria phylum) are present at very low levels. A novel PCR-based test has been developed and CE-marked for assessment of fecal microbiota profile, abundance and clinically relevant deviation from normobiosis. The 45 probes were selected based on their ability to distinguish between samples isolated from healthy individuals and IBS patients. The probes target the 6 predominant bacterial phyla covering over 300 species, and a Dysbiosis Index score (DI) is calculated. A DI ≤2 is indicative of normobiosis based on a healthy reference population (n>1,100); the higher the DI the greater the deviation from normobiosis.
The Dysbiosis Test and DI have been clinically validated in a study (n=330) comparing DI across cohorts of healthy controls, and IBS and IBD patients. Healthy subjects were included based on extensive questionnaire, and IBS and IBD patients were identified by Rome II and III diagnostic criteria and colonoscopy, respectively. Dysbiosis was prevalent among IBS patients (73%) and IBD patients (74%), but infrequent among healthy controls (16%). More discerning, significantly more IBD patients had DI >4 than did IBS patients; DI was not > 3 for the healthy cohort. Differences in microbiota profiles of IBS and IBD patients were evident, but the top targets discriminating normobiosis from dysbiosis for IBS and IBD patients were Actinobacteria, Bacteroides/Prevotella, Firmicutes (Bacilli and Clostridia), Faecalobacterium prausnitzii, Ruminococcus gnavus and Proteobacteria (and Shigella/Escherichia). That 16% of healthy controls were moderately dysbiotic is not surprising given the effects of relatively extreme diets on the microbiota (e.g. high fat, high/low protein, low carbohydrate, etc.). The model has also been successfully applied for identification of dysbioses associated with obesity, low FODMAPS, nonnutritive sweeteners and Ankylosing spondylitis.
There are no doubt many types of GI dysbiosis, and dietary extremes may be associated with dysbioses that are not yet associated with overt diagnostic symptoms, pathologies or metabolic derangements. A focused assessment of clinically relevant microbiota, inclusive of a validated dysbiosis test, facilitates appropriate intervention.