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References 2025-12-03 12:30:24
Microbiome Medicine majorpublished
Did you know?
In several diseases, the functional genome of microbes explains more variance in symptoms and treatment responses than human genetics. This means that for many conditions, the most actionable “precision medicine” target may not be human DNA at all, but the metabolic logic of the microbiome.
Microbiome Medicine
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Read MoreKaren 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 medicine reframes humans as holobionts and uses microbial signatures, sequencing, and computational tools to guide diagnosis, prevention, and treatment. By targeting microbial functions rather than isolated taxa, it enables genuinely personalized interventions that are already beginning to move from association studies into clinical practice.
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Karen Pendergrass
Read More
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Read More
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
Overview
Microbiome medicine represents a transformative field in modern healthcare that harnesses the power of microbial communities inhabiting the human body, particularly the gut microbiome, to diagnose, prevent, and treat disease.[1] Rather than viewing the body as a discrete entity, microbiome medicine recognizes humans as holobionts: biomolecular networks composed of a host organism plus its associated microbes collectively known as the hologenome.[2] This paradigm shift fundamentally reshapes how clinicians and researchers approach personalized medicine and disease management.
Understanding the Microbiome and Its Role in Health
The human microbiome comprises approximately 100 trillion microbial cells—bacteria, viruses, fungi, and archaea—that inhabit various body sites, with the gut microbiome being the largest and most extensively studied.[3] These microbial communities function as a virtual metabolic organ, performing numerous critical biochemical functions essential for human health.[4] The gut microbiota regulates immune function, drug metabolism, production of bioactive metabolites including short-chain fatty acids (SCFAs), and influences neurological health through the gut-brain axis.[5] A healthy microbiome demonstrates remarkable diversity and stability, yet remains dynamic and capable of responding to various intrinsic and extrinsic factors.[6] The microbiota’s functional capacity extends beyond simple metabolic support; it shapes host physiology through multiple signaling pathways including the immune system, tryptophan metabolism, vagus nerve signaling, and production of microbial metabolites such as short-chain fatty acids and bile acids.[7] When this delicate microbial balance is disrupted—a condition termed dysbiosis—systemic health consequences cascade throughout the body, affecting not only gastrointestinal function but also cardiovascular, metabolic, immune, and neurological systems.[8]
Precision Medicine and Microbiome Profiling
At its core, microbiome medicine leverages precision medicine strategies, where understanding an individual’s unique microbiota composition and function enables tailored therapeutic interventions.[9] Advanced sequencing technologies, particularly 16S rRNA gene sequencing and shotgun metagenomics, have enabled detailed characterization of microbial communities and their functional potential.[10] These high-throughput sequencing approaches have revealed robust microbial signatures linked to infectious, inflammatory, metabolic, and neoplastic diseases, opening unprecedented opportunities for improved diagnostics and personalized therapeutic development.[11] Machine learning and artificial intelligence technologies are increasingly integrated with microbiome data to identify discriminatory features and develop predictive models for disease.[12] These computational approaches enhance the capacity to analyze vast, complex datasets generated from microbiome studies, facilitating the timely identification of disease-associated microbial signatures and enabling the development of biomarkers for disease diagnosis, prognosis, and treatment response prediction.[13]
Translational Perspectives in Microbiome Medicine
Microbiome medicine represents a transformative paradigm in healthcare that recognizes the microbiota as a critical modulator of human health and disease. Through precision profiling of individual microbiota composition and function, combined with targeted therapeutic interventions ranging from dietary modifications to engineered probiotics and phage therapy, clinicians can now implement personalized approaches to preventing and treating previously intractable diseases.[14] The field is rapidly advancing from descriptive associations toward mechanistic understanding and clinical translation, with several microbiome-targeted interventions already approved by regulatory agencies.[15]
FAQs
How does the current focus on standardization and taxon-centric profiling affect progress in microbiome medicine?
How does the current focus on standardization and taxon-centric profiling affect progress in microbiome medicine?
Much of the field currently emphasizes methodological standardization and taxon-centric profiling as prerequisites for defining “true” microbiome signatures to help determine correct paths in microbiome medicine.
While robust methods are important, treating standardization as a gatekeeper risks systemic bias and unnecessary delay in clinical translation. It prioritizes consensus on technical pipelines over mechanistic understanding and can inadvertently filter out signal that does not fit prevailing models or dominant platforms. A more productive path for microbiome medicine is to focus on the functional architecture of microbiome signatures: what the community is doing rather than which single taxa are present.
This includes integrating metabolomics, metallomics, microbial metallomics, and inter-kingdom ecology, and then using a logic-based validation framework similar to the Bradford Hill criteria to connect microbiome changes with plausibly causal mechanisms and clinically meaningful outcomes.
Instead of waiting for perfect standardization and large randomized controlled trials for every condition, clinicians and researchers can triangulate evidence across multiple data streams, mechanistic plausibility, coherence with prior biology, and intervention responses.
This “time and resource-sensitive” approach allows microbiome medicine to move forward in an explicitly hypothesis-driven, cautious, and transparent way, using existing data to refine microbiome signatures and microbiome-targeted interventions while remaining open to revision as higher-level evidence accumulates.
How can clinicians begin applying microbiome medicine now, despite incomplete standardization and limited RCT data?
How can clinicians begin applying microbiome medicine now, despite incomplete standardization and limited RCT data?
Clinicians can already integrate microbiome medicine into practice by using microbiome findings as mechanistic context rather than as absolute diagnostic labels. First, they can map condition-specific microbiome signatures to plausible functional consequences, such as increased production of specific toxins, reduced butyrate generation, altered metal handling, or dysregulated bile acid signaling. Second, they can select microbiome-targeted interventions that are supported by converging evidence: observational data, mechanistic studies, early clinical trials, and consistency with established physiology.
Examples include targeted dietary patterns, specific fibers and prebiotics, rationally chosen probiotics or live biotherapeutics, and, in selected cases, more advanced approaches such as fecal microbiota transplantation (FMT) or phage therapy where regulatory frameworks permit. Finally, using a Bradford Hill style logic, clinicians can evaluate whether changes in microbiome composition and function align with symptom changes or biomarker shifts in their own patients, documenting both positive and negative outcomes.
This iterative, intuitive, evidence-informed, and critically reflective approach allows clinicians to practice microbiome medicine today while contributing to a growing body of real-world data that will ultimately refine standards, signatures, and formal guidelines.
What does a “functional” interpretation of a microbiome signature mean in practice?
What does a “functional” interpretation of a microbiome signature mean in practice?
A functional interpretation reframes a microbiome signature from a static list of taxa into a network of capabilities and constraints. Instead of asking only “which microbes are enriched or depleted,” clinicians and researchers of the Microbiome Medicine database ask: Which metabolic pathways are upregulated or suppressed? How are metal handling and nutritional immunity altered at the host and community level? How does the metallomic signature of tissues, mismetallation signals, and subsequent metal dyshomeostasis influence the microbial shift seen in the microbiome signature? Are key metabolites such as short-chain fatty acids, bile acid derivatives, tryptophan catabolites, or uremic toxins likely to be increased or decreased? Which microbial enzymes are metal dependent, and how might metallomic shifts (for example in iron, zinc, or nickel availability) favor specific pathobionts or virulence factors? And How do bacteria, fungi, and viruses interact in this signature, and what does that imply for barrier integrity, immune tone, functional shielding, co-aggregation, and host signaling pathways? By focusing on these functional dimensions, microbiome medicine can identify leverage points for intervention, such as diet, prebiotics, probiotics, phage, or metal-targeted strategies, even when taxonomic profiles differ across studies or platforms.
Research Feed
The Microbiome in Precision Medicine: The Way Forward
February 22, 2018
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Microbiome Signatures •
Microbiome Signatures
Did you know?
This expanded microbiome signatures definition promotes a more integrative, mechanistic, and clinically translational understanding of host-microbiome interactions.
Microbiome-Targeted Interventions (MBTIs) •
Microbiome-Targeted Interventions (MBTIs)
Did you know?
Microbiome Targeted Interventions (MBTIs) are revolutionizing modern medicine. These interventions can precisely modulate the microbiome, offering unprecedented precision in targeting pathogens while preserving beneficial microbes.
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Update History
Microbial Metallomics
Microbial Metallomics is the study of how microorganisms acquire, use, regulate, and transform metals in any biological or environmental context.
Fecal Microbiota Transplantation (FMT)
Fecal Microbiota Transplantation (FMT) involves transferring fecal bacteria from a healthy donor to a patient to restore microbiome balance.
Phage Therapy
Phage therapy uses viruses to target and kill specific bacteria, offering a precise alternative to antibiotics, especially for resistant infections.
Microbiome Signatures
Microbiome signatures are reproducible ecological and functional patterns—encompassing traits, interactions, and metabolic functions—that reflect microbial adaptation to specific host or environmental states. Beyond taxonomy, they capture conserved features like metal metabolism or immune modulation, enabling systems-level diagnosis and intervention in health and disease.
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.
References
- Precision medicine strategy based on microbiome.. Guo.. (Life Studies. 2025.)
- Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes.. S. R. Bordenstein and K. R. Theis.. (Public Library of Science, Aug. 2015.)
- The Human Gut Microbiome – A Potential Controller of Wellness and Disease.. Kho.. (Frontiers in Microbiology. 2018.)
- Microbiota in health and diseases.. Hou.. (Signal Transduction and Targeted Therapy. 2022.)
- The Microbiota-Gut-Brain Axis.. Cryan.. (Physiological Reviews. 2019.)
- Understanding dysbiosis and resilience in the human gut microbiome: biomarkers, interventions, and challenges.. Safarchi.. (Frontiers in Microbiology. 2025.)
- The Microbiota-Gut-Brain Axis.. Cryan.. (Physiological Reviews. 2019.)
- Microbiota in health and diseases.. Hou et al. (Signal Transduction and Targeted Therapy. 2022.)
- Understanding dysbiosis and resilience in the human gut microbiome: biomarkers, interventions, and challenges.. Safarchi.. (Frontiers in Microbiology. 2025.)
- Gut microbiome metagenomics in clinical practice: bridging the gap between research and precision medicine.. Tegegne.. (Gut Microbes. 2025.)
- Gut microbiome metagenomics in clinical practice: bridging the gap between research and precision medicine.. Tegegne.. (Gut Microbes. 2025.)
- Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action.. D’Elia.. (Frontiers in Microbiology. 2023.)
- Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action.. D’Elia.. (Frontiers in Microbiology. 2023.)
- Precision medicine strategy based on microbiome.. Guo.. (Life Studies. 2025.)
- Microbiome-Targeted Therapies in Gastrointestinal Diseases: Clinical Evidence and Emerging Innovations.. Lim.. (Acta Microbiologica Hellenica. 2025.)
S. R. Bordenstein and K. R. Theis.
Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes.Public Library of Science, Aug. 2015.
Kho.
The Human Gut Microbiome – A Potential Controller of Wellness and Disease.Frontiers in Microbiology. 2018.
Safarchi.
Understanding dysbiosis and resilience in the human gut microbiome: biomarkers, interventions, and challenges.Frontiers in Microbiology. 2025.
Safarchi.
Understanding dysbiosis and resilience in the human gut microbiome: biomarkers, interventions, and challenges.Frontiers in Microbiology. 2025.
Tegegne.
Gut microbiome metagenomics in clinical practice: bridging the gap between research and precision medicine.Gut Microbes. 2025.
Tegegne.
Gut microbiome metagenomics in clinical practice: bridging the gap between research and precision medicine.Gut Microbes. 2025.
D’Elia.
Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action.Frontiers in Microbiology. 2023.
D’Elia.
Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action.Frontiers in Microbiology. 2023.
Lim.
Microbiome-Targeted Therapies in Gastrointestinal Diseases: Clinical Evidence and Emerging Innovations.Acta Microbiologica Hellenica. 2025.