Did you know?
This expanded microbiome signatures definition promotes a more integrative, mechanistic, and clinically translational understanding of host-microbiome interactions.
Microbiome Signatures Definition: A Conceptual Advancement for Translational Microbiome Science
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Microbiome signatures represent reproducible ecological and functional patterns within microbial communities across environments such as the human gut, skin, or oral cavity. Rather than relying solely on the types and abundances of bacteria, viruses, fungi, or archaea, these signatures encompass microbial traits, interactions, and metabolic functions that reflect adaptations to specific host states or environmental pressures. By capturing conserved features—such as metal ion metabolism, immune modulation, or structural degradation—microbiome signatures serve as critical tools for diagnosing, interpreting, and intervening in health and disease from a mechanistic and systems-level perspective.
-
Karen Pendergrass
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
The term microbiome signatures has become increasingly prominent in microbiome research, yet its definition remains inconsistently applied and often oversimplified. However, a precise microbiome signatures definition is nonetheless essential for advancing both basic science and translational applications. Most commonly, microbiome signatures have been equated with lists of differentially abundant taxa associated with disease states. However, this approach fails to capture the complexity and dynamics of microbial ecosystems. A more robust, complete, and actionable microbiome signatures definition must account not only for the presence or absence of taxa but also for their traits, interactions, and functional roles within specific environmental or host contexts.
Proposed Microbiome Signatures Definition
A microbiome signature is a reproducible ecological or functional pattern—reflected through taxa, their features, or their interactions—that emerges in association with a specific host state, environmental condition, or intervention. These signatures may not rely on identical taxa across all contexts, but instead on conserved microbial traits, directional shifts, or networked relationships that reflect underlying dysbiosis or homeostasis.
Rationale and Conceptual Framework
Existing definitions of microbiome signatures often emphasize taxonomic reproducibility and statistical significance in differential abundance. While these are incredibly valuable, a reductionist framing can obscure the importance of ecological and functional consistency that persists across studies, populations, and analytical methods. Our definition of microbiome signatures expands the scope to include not only microbial identities but also their traits, interactions, and emergent ecological relationships, thus capturing the true complexity of host-microbiome systems.
This definition rests on the following conceptual pillars:
• Functional Redundancy and Trait Conservation: Taxa may vary, but conserved microbial functions (e.g., bile acid deconjugation, urease activity, MMP induction, heavy metal tolerance, or efflux pump expression) persist across environments and cohorts, underscoring functional stability despite taxonomic variability.
• Ecological Plasticity and Environmental Filtering: Microbial community structures reflect selective pressures (e.g., diet, metals, host inflammation), which drive predictable patterns of trait enrichment.
• Networked and Directional Relationships: Signatures often include directional shifts in taxa ratios (e.g., Firmicutes: Bacteroidetes), co-occurrence patterns, or keystone dynamics.
Comparison to Prevailing Microbiome Signature Definitions
Most existing frameworks rely on statistical overrepresentation of taxa across case-control comparisons. However, such approaches are limited by cohort variability, methodological heterogeneity, and geographic or dietary differences. The proposed definition incorporates these realities, allowing for interpretation of conserved functional trajectories even in the absence of fixed taxonomic recurrence. Thus, our microbiome signatures definition transcends static taxonomic lists and acknowledges the emergent, context-dependent relationships between microbes, their environment, and the host.
| Feature | Proposed Definition | |
|---|---|---|
| Conceptual Unit | Traits, features, interactions, and taxa | Taxa (species, genus, OTU) |
| Reproducibility | Functional/ecological consistency, and taxonomic recurrence | Taxonomic recurrence |
| Generalizability | High, even across geographies or interventions | Low if taxa are highly varied |
| Translational Utility | Supports mechanistic insights and interventions | Often descriptive only |
| Scope | Systemic, functional, ecological, taxonomic, and statistical | Narrow, taxonomic, statistical |
Advantages for Translational Microbiome Research
This enriched conceptualization of microbiome signatures enhances their relevance in clinical and translational applications by supporting the development of microbiome-targeted interventions (MBTIs) based on microbial function, environmental pressures, and inter-species relationships, not merely taxonomic identity. It also facilitates the formulation of STOP advisories by linking host pathophysiology to trait-enriched dysbiosis, providing a mechanistic rationale for discontinuing practices that exacerbate microbial imbalance. Additionally, it strengthens the Microbial Signature Confidence Score (MSCS) framework by incorporating ecological and functional coherence, thereby improving the reliability of signature-based diagnostics. Finally, this definition enables cross-condition mapping of conserved dysbiotic features, such as MMP-expressing pathobionts shared between endometriosis and cancer, broadening the utility of microbiome signatures in comparative disease analysis.
Conclusion
This definition represents a conceptual advancement in the understanding of microbiome signatures. It aligns with ecological theory, systems biology, and translational medicine, providing a foundation for actionable and mechanistically grounded microbiome science. By recognizing the emergent, adaptive, and context-dependent nature of microbial patterns, this new microbiome signatures definition and framework enables improved mechanistic insight, and a new generation of signature-based diagnostics, therapeutics, and interventions.
Microbiome-Targeted Interventions (MBTIs)
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.
STOPs
A STOP (Suggested Termination Of Practices) is a recommendation that advocates for the discontinuation of certain medical interventions, treatments, or practices based on emerging evidence indicating that these may be ineffective, harmful, or counterproductive in the management of specific conditions.