Infectious Diseases and Metabolomics

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

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

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