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Applications | Infectious Disease

Infectious Diseases and Metabolomics

Explore the power of metabolomics in infectious disease research for precision diagnostics and personalized interventions.

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Infectious Disease and Metabolomics

Metabolomics in Infectious Diseases

Infectious diseases present a formidable challenge in the field of medical research due to their complex and dynamic nature. Traditional approaches often focus on understanding the genetic or proteomic aspects of pathogens, but these methods may fall short in capturing the intricate interactions between host and pathogen during infection. Moreover, the heterogeneity in host responses and the diverse strategies employed by pathogens make it difficult to unravel the molecular intricacies underlying infectious diseases comprehensively. This limitation hinders the identification of biomarkers for early detection, prognosis, and treatment, thus impeding the development of effective therapeutic strategies.

Metabolomics is a transformative tool in infectious disease research, offering a holistic perspective that addresses the shortcomings of conventional methods. By studying the complete set of metabolites within a biological system, metabolomics provides a comprehensive snapshot of the biochemical processes occurring during infection. This approach allows researchers to monitor changes in the host’s metabolic profile and the metabolic footprint of the invading pathogens. Metabolomics not only facilitates the identification of unique biomarkers associated with infectious diseases but also sheds light on the underlying mechanisms driving disease progression. The ability to capture the dynamic interplay between host and pathogen metabolism enhances our understanding of infection dynamics, paving the way for the development of targeted and personalized therapeutic interventions. In essence, metabolomics proves instrumental in advancing our knowledge of infectious diseases, offering a powerful tool to decipher the intricate molecular landscape and ultimately improve patient outcomes.

Infectious Disease

Uncover Functional, Actionable Insights with Metabolomics

More research is needed to understand the various factors impacting infectious disease risk, etiology, and pathogenesis. Metabolon can help researchers capture and describe complex interactions between host and pathogen during infection through metabolomics analysis. Global metabolomics can be used to identify metabolic perturbations during infection, while targeted panels can be used to identify and verify diagnostic, predictive, and therapeutic biomarkers.

Comprehensive Insight into Host-Pathogen Interactions
Biomarker Discovery
Personalized Treatment Strategies

Comprehensive Insight into Host-Pathogen Interactions

Metabolomics provides a comprehensive snapshot of the intricate interactions between host organisms and pathogens during infection. By analyzing the complete set of metabolites in biological samples, researchers can identify subtle changes in metabolic pathways, offering a deeper understanding of how pathogens manipulate host metabolism and how the host responds to infection. This holistic perspective enhances our ability to uncover key molecular events and signaling pathways, ultimately progressing the field of infectious disease research. A  prime  example is  recurrent  Clostridium difficile infection. Metabolite changes in the host microbiome were predictive of the risk of recurrent infection. This information was used to develop a microbiome drug to reduce recurrent risk.

McGovern BH, Ford CB, Henn MR, et al. SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial. Clin Infect Dis. 2021;72(12):2132-2140. doi:10.1093/cid/ciaa387

Feuerstadt P, Louie TJ, Lashner B, et al. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med. 2022;386(3):220-229. doi:10.1056/NEJMoa2106516

Biomarker Discovery

Metabolomics plays a crucial role in the identification of biomarkers associated with infectious diseases. These biomarkers can be used for early detection, accurate diagnosis, determination of disease severity, and monitoring of disease progression. In a study published in Cell Systems, a multiomics approach including RNA-seq, immunophenotyping, and metabolomics was used to identify genetic and metabolic signatures associated with COVID-19 disease severity, identifying the TCA cycle as a key metabolic pathway target for novel COVID-19 therapies. The researchers also built personalized networks from these data, demonstrating how integration of metabolomics with other omics data can pave the way for personalized medicine research.

Ambikan AT, Yang H, Krishnan S et al. Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity. Cell Syst. 2022;13(8):665-681. doi: 10.1016/j.cels.2022.06.006

Personalized Treatment Strategies

​Metabolomics allows for the development of personalized treatment strategies in infectious disease management. The detailed understanding of host-pathogen interactions and the associated metabolic changes enables the identification of specific targets for therapeutic intervention. This personalized approach considers individual variation in host response to infection, leading to more effective and tailored treatment regimens. Metabolomics, therefore, contributes to the advancement of precision medicine in infectious disease research, offering the potential for improved therapeutic outcomes and reduced adverse effects by optimizing treatments based on an individual’s unique metabolic profile. For example, Fulani children are less susceptible to malaria infection than Gouin children. In a study published in Nature Metabolism, metabolomics detected opposite trends in these groups in metabolites associated with parasitemia and immune response, specifically, anti-inflammatory steroids. Understanding differences in disease mechanisms between  people and groups can guide prevention and treatment decisions.

Abdrabou W, Dieng MM, Diawara A, et al. Metabolome modulation of the host adaptive immunity in human malaria. Nat Metab. 2021;3(7):1001-1016. doi: 10.1038/s42255-021-00404-9

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Metabolomics Applications for Infectious Disease Research

  • EBiomarker discovery
  • EPersonalized medicine research
  • EDisease risk assessment
  • EMonitoring treatment response
  • EUnderstanding disease progression
  • EDrug discovery and development
  • EEarly disease detection
  • EUnderstanding molecular mechanisms of disease
  • EGene-metabolite associations
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“Taken together, these data highlight the importance of evaluating microbiome pharmacokinetics (ie, engraftment of SER-109 species) and pharmacodynamics (ie, changes in microbe-associated metabolites and overall microbiome changes) in parallel with assessment of clinical efficacy.”

McGovern BH, Ford CB, Henn MR, et al.
SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial. Clin Infect Dis. 2021;72(12):2132-2140. doi:10.1093/cid/ciaa387

Metabolomics Insights into Infectious Diseases

Clostridiodes difficile infection (CDI) leads to over 223,900 hospital cases and 12,800 deaths annually in the United States. Symptoms include diarrhea, colitis, dehydration, and sepsis. Antibiotics treat CDI symptoms by killing germinating C. difficile bacteria, but they do not eliminate spores, allowing rapid regrowth and microbiome imbalance, contributing to recurrent CDI (rCDI). Seres Therapeutics developed a microbiome therapeutic to treat rCDI and completed an 8-week clinical trial. Results of this study indicated that subjects receiving the therapeutic had more diverse species of gut microbes, a response which endured over the 8-week study. This response in beneficial the microbes produce metabolites such as bile acids which inhibit C. difficile spore germination and growth.

Metabolon’s Good Clinical Practice (GCP)-validated Bile Acids Targeted Panel helped demonstrate the therapeutic’s mechanism of action (MOA) by confirming increased secondary bile acids, associated with an inhibition of C. difficile spore germination. The research group also leveraged Metabolon’s proprietary Global Discovery Panel to gain a clear picture of the biological activity of the microbial community and to identify potential metabolite-based biomarkers that could inform drug pharmacokinetics and pharmacodynamics.

The FDA approval of Seres Therapeutics’ microbiome-based therapy signifies the essential contribution of metabolomics in developing an effective and easy-to-administer treatment for rCDI and paves the way for a novel category of therapeutics that utilize microbiome interventions. Metabolon is an established and reliable metabolomics collaborator, having executed over 10,000 projects over the last 20 years. Our proprietary and comprehensive Global Discovery platform uniquely positions Metabolon to address the complex and diverse research questions facing the infectious disease research community, while our Targeted Panel offerings allow for a more focused approach to further the journey to drug development.

McGovern BH, Ford CB, Henn MR, et al. SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial. Clin Infect Dis. 2021;72(12):2132-2140. doi:10.1093/cid/ciaa387

Feuerstadt P, Louie TJ, Lashner B, et al. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med. 2022;386(3):220-229. doi:10.1056/NEJMoa2106516

Infectious Diseases Publications and Citations

Metabolon has contributed extensively to publications ranging from basic research to clinical trials.

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