Address non-communicable diseases and disorders.

Microbiome Engineering

Health & Medicine Challenge:

Address non-communicable diseases and disorders.

Develop prophylactic or health-improving interventions for non-communicable diseases and disorders.

Engineer microbiomes to prevent allergies and autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, diabetes).

Technical Achievement: Engineer microbiomes to synthesize and secrete controllable levels of immune-stimulating antigens to tune down allergy-inducing immune responses.
Technical Achievement: Engineer microbiomes to sequester and degrade allergy-causing particles to prevent immune responses.
Technical Achievement: Identify changes in the gut microbiome that contribute to autoimmune diseases and engineer microbiomes to resist those shifts.

Engineer gut microbiomes to reduce mental health problems and neurodegenerative diseases.

Technical Achievement: Engineer gut microbiomes to prevent dysbiosis associated with depression or other mental health disorders.¹,²
Technical Achievement: Engineer gut microbiomes to detect and break down aggregated proteins associated with Parkinson’s Disease, to mitigate disease progression.³

Engineer probiotic gut microbiomes.

Technical Achievement: Design gut microbiomes that produce beneficial molecules such as butyrate.⁴
Technical Achievement: Engineer gut microbiomes that consume unwanted or unhealthy metabolites.
Technical Achievement: Engineer gut microbiomes that degrade or sequester toxins to prevent food poisoning.

Design microbiomes that improve quality of life.

Technical Achievement: Engineer microbiomes that regulate caloric intake to prevent obesity.
Technical Achievement: Engineer microbiomes that allow humans to obtain energy from nontraditional carbon sources when food is not available (e.g., consume grass and lignocellulosic material for energy).
Technical Achievement: Create microbiomes that enhance or alter mental health (e.g., memory, mental acuity, emotional state) for short or long time periods.
Technical Achievement: Engineer microbiomes that prevent fatigue and increase alertness.

Dynamically treat diseases and disorders.

Engineer microbiomes (e.g., gut, skin, oral) to produce a missing metabolite or consume a toxic intermediate that builds up in a disease state.

Technical Achievement: Engineer microbiomes that compete with oral microbes to prevent plaque formation and degrade plaque-derived extracellular matrices.
Technical Achievement: Engineer microbiomes that monitor the levels of key metabolites and maintain homeostasis (i.e., produce or degrade them if the levels are too low or high).

Engineer microbiomes to enhance drug efficacy by preventing undesired drug metabolism or metabolizing leftover chemicals once treatment is complete.

Technical Achievement: Engineer gut microbiomes to couple their metabolism with metabolic or hormonal changes in a host (e.g., human patient).
Technical Achievement: Engineer microbiomes to monitor, record, and report on drug metabolite and degradation product concentrations to improve drug dosing.

Rapid point-of-care diagnostic tools to assess patient health (e.g., immune status, blood pressure, cholesterol level).

Model individual health from native microbiome composition and function (e.g., microbiome sequencing or transcriptomics for diagnosis).

Technical Achievement: Determine microbiome composition and individual species’ functions under healthy conditions.
Technical Achievement: Generate computational models that can determine an individual’s immune status from microbiome composition.
Technical Achievement: Model a host’s disease or health status based on a microbiome’s functional status (e.g., transcriptional states).

Engineer microbiome-based diagnostics.

Technical Achievement: Engineer ingestible microbiomes that capture environmental data from the human gut and provide a measurable read-out (e.g., altered gene expression, protein modification) after excretion.⁵^,⁶^,⁷
Technical Achievement: Engineer modular microbiome-based diagnostic systems to increase flexibility and adaptability of diagnostic tests (e.g., one platform that can test blood count, enzyme markers, and sexually transmitted diseases by switching out species in microbiome).
Technical Achievement: Identify sensitive and specific microbiome biomarkers for any disease (e.g., determine gut microbiome changes during co-located diseases like colon cancer or systemic diseases like lymphomas or leukemias).
Technical Achievement: Engineer non-pathogenic microbiomes that can be administered to a person and used to assess immunosuppression or other alterations in immune status (i.e., tuberculin skin test for a broader range of conditions).
Technical Achievement: Engineer microbiomes to constitutively monitor immune-response biomarkers (e.g., gut microbiome that changes color in response to low CD8+ T cell counts).
Technical Achievement: Engineer skin microbiomes to detect biomarkers of early-stage skin diseases (e.g., microbiome that produces dark pigment in response to UV damage).

Combine biomarkers into microbiome-based biosensor platforms.

Technical Achievement: Engineer gut microbiomes that can assess and report cardiovascular disease-associated microbiome shifts, such as increases in uric acid production.⁸
Technical Achievement: Engineer oral microbiomes that can assess early stage periodontal disease by detecting pathogens (e.g., Streptococcus mutans) and salivary biomarkers (e.g., MIP‐1α).⁹

Footnotes

Johnson, K. V.-A. (2020). Gut microbiome composition and diversity are related to human personality traits. Human Microbiome Journal, 15, 100069. https://doi.org/10.1016/j.humic.2019.100069
Valles-Colomer, M., Falony, G., Darzi, Y., Tigchelaar, E. F., Wang, J., Tito, R. Y., Schiweck, C., Kurilshikov, A., Joossens, M., Wijmenga, C., Claes, S., Van Oudenhove, L., Zhernakova, A., Vieira-Silva, S., & Raes, J. (2019). The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology, 4(4), 623–632. https://doi.org/10.1038/s41564-018-0337-x
Ghaisas, S., Maher, J., & Kanthasamy, A. (2016). Gut microbiome in health and disease: Linking the microbiome–gut–brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacology & Therapeutics, 158, 52–62. https://doi.org/10.1016/j.pharmthera.2015.11.012
Guo, C.-J., Allen, B. M., Hiam, K. J., Dodd, D., Van Treuren, W., Higginbottom, S., Nagashima, K., Fischer, C. R., Sonnenburg, J. L., Spitzer, M. H., & Fischbach, M. A. (2019). Depletion of microbiome-derived molecules in the host using Clostridium genetics. Science, 366(6471), eaav1282. https://doi.org/10.1126/science.aav1282
Mimee, M., Tucker, A. C., Voigt, C. A., & Lu, T. K. (2015). Programming a Human Commensal Bacterium, Bacteroides thetaiotaomicron, to Sense and Respond to Stimuli in the Murine Gut Microbiota. Cell Systems, 1(1), 62–71. https://doi.org/10.1016/j.cels.2015.06.001
Naydich, A. D., Nangle, S. N., Bues, J. J., Trivedi, D., Nissar, N., Inniss, M. C., Niederhuber, M. J., Way, J. C., Silver, P. A., & Riglar, D. T. (2019). Synthetic Gene Circuits Enable Systems-Level Biosensor Trigger Discovery at the Host-Microbe Interface. MSystems, 4(4), e00125-19, /msystems/4/4/mSys.00125-19.atom. https://doi.org/10.1128/mSystems.00125-19
Riglar, D. T., Giessen, T. W., Baym, M., Kerns, S. J., Niederhuber, M. J., Bronson, R. T., Kotula, J. W., Gerber, G. K., Way, J. C., & Silver, P. A. (2017). Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation. Nature Biotechnology, 35(7), 653–658. https://doi.org/10.1038/nbt.3879
Tang, W. H. W., Kitai, T., & Hazen, S. L. (2017). Gut Microbiota in Cardiovascular Health and Disease. Circulation Research, 120(7), 1183–1196. https://doi.org/10.1161/CIRCRESAHA.117.309715
Kc, S., Wang, X. Z., & Gallagher, J. E. (2020). Diagnostic sensitivity and specificity of host‐derived salivary biomarkers in periodontal disease amongst adults: Systematic review. Journal of Clinical Periodontology, 47(3), 289–308. https://doi.org/10.1111/jcpe.13218