Microbiota and dose-response: evolving paradigm of health triangle

Authors: COLEMAN, MARGARET - Coleman Scientific Consulting; ELKINS, CHRISTOPHER - Food And Drug Administration(FDA); GUTTING, B - Us Navy; MONGODIN, E - University Of Maryland; Solano-Aguilar, Gloria; WALLS, I - National Institute Of Food And Agriculture (NIFA)

Submitted to: Risk Analysis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/20/2018
Publication Date: 6/13/2018
Citation: Coleman, M., Elkins, C.A., Gutting, B.W., Mongodin, E.F., Solano Aguilar, G., Walls, I. 2018. Microbiota and dose-response: evolving paradigm of health triangle. Risk Analysis. 10.1111. https://doi.org/10.1111/risa.13121.
DOI: https://doi.org/10.1111/risa.13121

Interpretive Summary: SRA Dose Response and Microbial Risk Analysis Specialty Groups jointly sponsored a symposia to address the intersections between the 'microbiome revolution' and dose-response assessment. Invited speakers presented data on innovations and advances in gut and nasal microbiota in the first decade after the Human Microbiome Project began. The microbiota and their metabolites are now known to influence health and disease directly and indirectly, through the modulation of the immune system. The disruption of healthy microbiota is often associated with changes in abundance and diversity of core microbial species (dysbiosis), caused by stressors including antibiotics, chemotherapy, and disease. Metagenomic methods demonstrated that dysbiotic host microbiota no longer provide normal colonization resistance to pathogens, a critical component of innate immunity of the superorganism. Diverse pathogens, as well as probiotics, prebiotics and model systems, were considered in human and animal models (in vivo and in vitro). Discussion included approaches for the design of future microbial dose-response studies to account for the presence of the indigenous microbiota that provide normal colonization resistance, and the absence of the protective microbiota in dysbiosis. Next Generation microbial dose-response assessments will benefit by the expansion of the framework of the old paradigm (Disease Triangle, including host, pathogen, and environment) to include the microbiome. A proposed new framework, the Health Triangle, may assist researchers in designing experiments to test hypotheses about causality in dose-response relationships for pathogens present in food, water, and the environment that clearly compete with hundreds, sometimes thousands, of species dominating the dense, diverse protective microbiota.

Technical Abstract: SRA Dose-Response and Microbial Risk Analysis Specialty Groups jointly sponsored a symposia that addressed the intersections between the 'microbiome revolution' and dose-response assessment. Invited speakers presented on innovations and advances in gut and nasal microbiota (indigenous microbial communities) in the first decade after the Human Microbiome Project began. The microbiota and their metabolites are now known to influence health and disease directly and indirectly, through the modulation of innate and adaptive immune systems. Disruption of healthy microbiota is often associated with changes in abundance and diversity of core microbial species (dysbiosis), caused by stressors including antibiotics, chemotherapy, and disease. Nucleic acid-based metagenomic methods demonstrated that dysbiotic host microbiota no longer provide normal colonization resistance to pathogens, a critical component of innate immunity of the superorganism. Diverse pathogens, as well as probiotics, prebiotics and model systems, were considered in human and animal models (in vivo and in vitro). Discussion included approaches for design of future microbial dose-response studies to account for the presence of the indigenous microbiota that provide normal colonization resistance, and the absence of the protective microbiota in dysbiosis. Next Generation microbial dose-response assessments will benefit by expansion of the framework of the old paradigm (Disease Triangle, including host, pathogen, and environment) to include the microbiome. A proposed new framework, the Health Triangle, may assist researchers in designing experiments to test hypotheses about causality in dose-response relationships for pathogens present in food, water, and the environment that clearly compete with hundreds, sometimes thousands, of species dominating the dense, diverse protective microbiota.