Towards standardized gut microbiota diagnostics: normobiosis beyond geographical borders.

Defining clinically meaningful reference states of the human gut microbiota remains a major barrier to the clinical translation of microbiome testing, largely due to variability across populations. We aimed at evaluating whether dysbiosis can be identified in a standardized, geography-independent manner, using a composite, system-level microbiome diagnostic framework. We performed a retrospective observational analysis of 831 adult stool samples collected from healthy individuals and patients with inflammatory bowel disease, irritable bowel syndrome, or other chronic inflammatory conditions across seven countries. In addition, U.S. National Institute of Standards Technology (NIST) human fecal reference materials were analyzed. Dysbiosis was assessed using a fixed microbial marker panel and composite distance metrics anchored to a clinically validated healthy Scandinavian reference population, using GA-map® Dysbiosis Test as an exemplar of this diagnostic framework. The diagnostic framework reproducibly identified normobiosis and dysbiosis across geographically distinct populations (USA, Canada, Germany, Italy, and the UK). Severe dysbiosis was detected with high specificity (93.6%) and positive predictive value (90.2%), independent of subjects' country of origin. Healthy individuals showed highly comparable dysbiosis index distributions across regions. These findings demonstrate that clinically useful dysbiosis diagnostics do not require geographically tailored reference populations and support the feasibility of standardized, geography-independent microbiome diagnostics for clinical application.