Microbiota and Dose Response: Evolving Paradigm of Health Triangle

Abstract

SRA Dose-Response and Microbial Risk Analysis Specialty Groups jointly sponsored symposia that addressed the intersections between the "microbiome revolution" and dose response. Invited speakers presented on innovations and advances in gut and nasal microbiota (normal 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 modulation of innate and adaptive immune systems and barrier function. 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 the dysbiotic host microbiota no longer provide normal colonization resistance to pathogens, a critical component of innate immunity of the superorganism. Diverse pathogens, probiotics, and prebiotics 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. As NextGen risk analysis methodology advances with the "microbiome revolution," a proposed new framework, the Health Triangle, may replace the old paradigm based on the Disease Triangle (focused on host, pathogen, and environment) and germophobia. Collaborative experimental designs are needed for testing hypotheses about causality in dose-response relationships for pathogens present in our environments that clearly compete in complex ecosystems with thousands of bacterial species dominating the healthy superorganism.

Whole genome sequencing and metagenomics for outbreak investigation, source attribution and risk assessment of food‐borne microorganisms

“…Finally, metagenomics approaches also can provide information on the interaction of biological hazards with the human gut microbiota, which potentially might be valuable for hazard characterisation, since the health outcome can greatly depend on the prior gut microbiota status (i.e. intestinal dysbiosis can facilitate colonisation by food-borne pathogens) (Coleman et al, 2018).…”

Examining Evidence of Benefits and Risks for Pasteurizing Donor Breastmilk

“…Knowledge about the microbiota of milks is contributing to a dramatic transformation of roles, not just of medical professionals, but also of parents and regulators, as 'microbial managers' of healthy microbiomes, to reduce susceptibility to or prevent disease and actively promote health [23]. This microbial management strategy is consistent with a need to shift emphasis from the epidemiologic disease triangle to a health triangle featuring the microbiota [49], as endorsed by others [55,56].…”

“…The body of evidence for factors influencing the microbiota of milks related to the 'environment' aspect of the traditional 'disease triangle' (e.g., air quality and pollution; diet; supplements and pharmaceuticals; behavior/lifestyle/environment including farm and non-farm environments, built and natural environments, dust, soil; and water) is extensive and relevant to modeling dose-response relationships for pathogens amidst the natural microbiota of raw breastmilk and GI systems [49]. Some notable recent studies relevant for future dialogue with stakeholders include the following [50][51][52].…”

“…Similarly, direct and indirect microbial competition of the breastmilk microbiota with potential enteropathogens provide a primary disease prevention strategy with opportunities for more holistic, ecological approaches to 'optimized colonization resistance' in neonatology [9]. The importance of including evidence on dose-and time-dependent colonization resistance in microbial benefit and risk assessments was emphasized in recent studies [23,49].…”

Integrating Whole-Genome Sequencing Data Into Quantitative Risk Assessment of Foodborne Antimicrobial Resistance: A Review of Opportunities and Challenges

“…This would lead to a substantial improvement in the accuracy of exposure assessment models (Den Besten et al, 2018). Metagenomics could also be used to describe how the hazard interacts with the rest of the microbiome in the human gastrointestinal tract, accounting for the presence of an indigenous microbiota that provide a certain degree of colonization resistance, and the absence of protective microbiota in case of dysbiosis (Coleman et al, 2018). It represents an opportunity to move toward a new ‘health triangle’ paradigm in dose–response modeling that would replace the more conventional ‘disease triangle’ approach (focused on host, pathogen and environment) (Coleman et al, 2018).…”