Beyond the gut microbe: Rethinking infection, microbiome harmony, and the one-health continuum

Abstract

Emerging microbial discoveries have transformed infectious-disease science, yet detection alone does not equate to pathogenicity. Human health is mediated by complex microbiomes, and dysbiosis can convert commensals into opportunists, a concept captured by the “pathobiome”. Across infectious-disease literature, gaps remain in integrating ecological context, host response, longitudinal data, and one-health perspectives. Misinterpretation of culture or sequencing results drives antimicrobial misuse, resistance, and ecological harm. We propose an eight-principle framework to distinguish pathogen from non-pathogen: (1) Clinical localization; (2) Temporal host response; (3) Exclusion of alternative sources; (4) Ecological context; (5) Host susceptibility; (6) Contamination assessment; (7) Transparent reporting of methods and quantitative thresholds; and (8) Ethical use of diagnostic technology. Adoption of this framework to any specialty, including gut, promotes accurate infection identification, stewardship, and transparency. Expanding perspective from the individual microbiome to planetary health, this approach aligns discovery with ecological and ethical responsibility, transforming infectious-disease practice from reactionary treatment to preservation of microbial harmony.

Keywords: Microbiome; Pathobiome; Diagnostic stewardship; One Health; Pathogen identification

Core Tip: Advances in culture and sequencing have expanded microbial detection, but presence does not equal pathogenicity. Many infections reflect disruption of the human microbiome rather than invasion by a novel pathogen. Misinterpretation of isolates drives antimicrobial misuse, resistance, and ecological harm. This opinion proposes an eight-question, clinically grounded framework to distinguish pathogens from non-pathogens by integrating host site and response, ecological context, contamination assessment, and transparent reporting. Applying this approach aligns infectious-disease practice with diagnostic stewardship, one health principles, and preservation of microbial harmony from individual patients to planetary health.