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A framework for microbiome science in public health

Abstract

Human microbiome science has advanced rapidly and reached a scale at which basic biology, clinical translation and population health are increasingly integrated. It is thus now possible for public health researchers, practitioners and policymakers to take specific action leveraging current and future microbiome-based opportunities and best practices. Here we provide an outline of considerations for research, education, interpretation and scientific communication concerning the human microbiome and public health. This includes guidelines for population-scale microbiome study design; necessary physical platforms and analysis methods; integration into public health areas such as epidemiology, nutrition, chronic disease, and global and environmental health; entrepreneurship and technology transfer; and educational curricula. Particularly in the near future, there are both opportunities for the incorporation of microbiome-based technologies into public health practice, and a growing need for policymaking and regulation around related areas such as prebiotic and probiotic supplements, novel live-cell therapies and fecal microbiota transplants.

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Fig. 1: Opportunities for microbiome science in public health.
Fig. 2: Study design considerations for microbiome epidemiology.
Fig. 3: Curriculum suggestions for microbiome sciences in public health.

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References

  1. Thomas, A. M. et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat. Med. 25, 667–678 (2019).

    Article  CAS  PubMed  Google Scholar 

  2. Aron-Wisnewsky, J. et al. Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders. Nat. Rev. Gastroenterol. Hepatol. 17, 279–297 (2020).

    Article  PubMed  Google Scholar 

  3. Garrett, W. S. Cancer and the microbiota. Science 348, 80–86 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Khoruts, A. Targeting the microbiome: from probiotics to fecal microbiota transplantation. Genome Med. 10, 80 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kolodziejczyk, A. A., Zheng, D. & Elinav, E. Diet–microbiota interactions and personalized nutrition. Nat. Rev. Microbiol. 17, 742–753 (2019).

    Article  CAS  PubMed  Google Scholar 

  6. Donia, M. S. & Fischbach, M. A. Small molecules from the human microbiota. Science 349, 1254766 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Carmody, R. N. & Turnbaugh, P. J. Host–microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics. J. Clin. Invest. 124, 4173–4181 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Mallick, H. et al. Experimental design and quantitative analysis of microbial community multiomics. Genome Biol. 18, 228 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Sinha, R. et al. Assessment of variation in microbial community amplicon sequencing by the Microbiome Quality Control (MBQC) project consortium. Nat. Biotechnol. 35, 1077–1086 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Costea, P. I. et al. Towards standards for human fecal sample processing in metagenomic studies. Nat. Biotechnol. 35, 1069–1076 (2017).

    Article  CAS  PubMed  Google Scholar 

  11. Zhernakova, A. et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352, 565–569 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lloyd-Price, J. et al. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature 550, 61–66 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Aagaard, K. et al. The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters. FASEB J. 27, 1012–1022 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Everett, C. et al. Prospective characterization of the microbiome within cohort studies: overview of the Microbiome Among Nurses study (Micro-N). Nat. Protoc. (in the press).

  15. Franzosa, E. A. et al. Sequencing and beyond: integrating molecular ‘omics’ for microbial community profiling. Nat. Rev. Microbiol. 13, 360–372 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lloyd-Price, J. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569, 655–662 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lloyd-Price, J., Abu-Ali, G. & Huttenhower, C. The healthy human microbiome. Genome Med. 8, 51 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Lam, K. N., Alexander, M. & Turnbaugh, P. J. Precision medicine goes microscopic: engineering the microbiome to improve drug outcomes. Cell Host Microbe 26, 22–34 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Haiser, H. J. et al. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 341, 295–298 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Maier, L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555, 623–628 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gensollen, T. & Blumberg, R. S. Correlation between early-life regulation of the immune system by microbiota and allergy development. J. Allergy Clin. Immunol. 139, 1084–1091 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kim, S. & Jazwinski, S. M. The gut microbiota and healthy aging: a mini-review. Gerontology 64, 513–520 (2018).

    Article  CAS  PubMed  Google Scholar 

  23. Sze, M. A. & Schloss, P. D. Looking for a signal in the noise: revisiting obesity and the microbiome. MBio https://doi.org/10.1128/mBio.01018-16 (2016).

  24. Wang, D. D. et al. The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk. Nat. Med. 27, 333–343 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gibson, G. R. et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 14, 491–502 (2017).

    Article  PubMed  Google Scholar 

  26. Marco, M. L. et al. Health benefits of fermented foods: microbiota and beyond. Curr. Opin. Biotechnol. 44, 94–102 (2017).

    Article  CAS  PubMed  Google Scholar 

  27. McNulty, N. P. et al. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Sci. Transl. Med. 3, 106ra106 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Suez, J. et al. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell 174, 1406–1423 (2018).

    Article  CAS  PubMed  Google Scholar 

  29. Ballal, S. A. et al. Host lysozyme-mediated lysis of Lactococcus lactis facilitates delivery of colitis-attenuating superoxide dismutase to inflamed colons. Proc. Natl Acad. Sci. USA 112, 7803–7808 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang, Y. et al. Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: implications of probiotics in acne vulgaris. Appl. Microbiol. Biotechnol. 98, 411–424 (2014).

    Article  CAS  PubMed  Google Scholar 

  31. Norman, J. M. et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160, 447–460 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Howitt, M. R. et al. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351, 1329–1333 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Vehik, K. et al. Prospective virome analyses in young children at increased genetic risk for type 1 diabetes. Nat. Med. 25, 1865–1872 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cryan, J. F. et al. The microbiota–gut–brain axis. Physiol. Rev. 99, 1877–2013 (2019).

    Article  CAS  PubMed  Google Scholar 

  35. Pasolli, E., Truong, D. T., Malik, F., Waldron, L. & Segata, N. Machine learning meta-analysis of large metagenomic datasets: tools and biological insights. PLoS Comput. Biol. 12, e1004977 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Geller, L. T. et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 357, 1156–1160 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103 (2018).

    Article  CAS  PubMed  Google Scholar 

  38. Garrett, W. S. The gut microbiota and colon cancer. Science 364, 1133–1135 (2019).

    Article  CAS  PubMed  Google Scholar 

  39. Libertucci, J. & Young, V. B. The role of the microbiota in infectious diseases. Nat. Microbiol. 4, 35–45 (2019).

    Article  CAS  PubMed  Google Scholar 

  40. Hendriksen, R. S. et al. Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage. Nat. Commun. 10, 1124 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Hagan, T. et al. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell 178, 1313–1328 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Eyre, D. W. et al. A Candida auris outbreak and its control in an intensive care setting. N. Engl. J. Med. 379, 1322–1331 (2018).

    Article  PubMed  Google Scholar 

  43. Drekonja, D. et al. Fecal microbiota transplantation for Clostridium difficile infection: a systematic review. Ann. Intern. Med. 162, 630–638 (2015).

    Article  PubMed  Google Scholar 

  44. Krismer, B., Weidenmaier, C., Zipperer, A. & Peschel, A. The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota. Nat. Rev. Microbiol. 15, 675–687 (2017).

    Article  CAS  PubMed  Google Scholar 

  45. Hsu, B. B. et al. Dynamic modulation of the gut microbiota and metabolome by bacteriophages in a mouse model. Cell Host Microbe 25, 803–814 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gosmann, C. et al. Lactobacillus-deficient cervicovaginal bacterial communities are associated with increased HIV acquisition in young South African women. Immunity 46, 29–37 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mukherjee, D., Chora, A. F. & Mota, M. M. Microbiota, a third player in the host–plasmodium affair. Trends Parasitol. 36, 11–18 (2020).

    Article  PubMed  Google Scholar 

  48. Negatu, D. A. et al. Gut microbiota metabolite indole propionic acid targets tryptophan biosynthesis in Mycobacterium tuberculosis. MBio https://doi.org/10.1128/mBio.02781-18 (2019).

  49. Blanton, L. V., Barratt, M. J., Charbonneau, M. R., Ahmed, T. & Gordon, J. I. Childhood undernutrition, the gut microbiota, and microbiota-directed therapeutics. Science 352, 1533 (2016).

    Article  CAS  PubMed  Google Scholar 

  50. Gehrig, J. L. et al. Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Science https://doi.org/10.1126/science.aau4732 (2019).

  51. National Academies of Sciences, Engineering, and Medicine Environmental Chemicals, the Human Microbiome, and Health Risk: A Research Strategy (National Academies Press, 2018).

  52. Claus, S. P., Guillou, H. & Ellero-Simatos, S. The gut microbiota: a major player in the toxicity of environmental pollutants? NPJ Biofilms Microbiomes 2, 16003 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Meadow, J. F. et al. Bacterial communities on classroom surfaces vary with human contact. Microbiome 2, 7 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Fahimipour, A. K. et al. Antimicrobial chemicals associate with microbial function and antibiotic resistance indoors. mSystems https://doi.org/10.1128/mSystems.00200-18 (2018).

  55. Georges, M., Charlier, C. & Hayes, B. Harnessing genomic information for livestock improvement. Nat. Rev. Genet. 20, 135–156 (2019).

    Article  CAS  PubMed  Google Scholar 

  56. Attwood, G. T. et al. Applications of the soil, plant and rumen microbiomes in pastoral agriculture. Front. Nutr. 6, 107 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Dreher-Lesnick, S. M., Stibitz, S. & Carlson, P. E. Jr U.S. regulatory considerations for development of live biotherapeutic products as drugs. Microbiol. Spectr. 5 https://doi.org/10.1128/microbiolspec.BAD-0017-2017 (2017).

  58. Markey, K. A. et al. The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD. Blood 136, 130–136 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Ossorio, P. N. & Zhou, Y. Regulating stool for microbiota transplantation. Gut Microbes 10, 105–108 (2019).

    Article  PubMed  Google Scholar 

  60. DeFilipp, Z. et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N. Engl. J. Med. 381, 2043–2050 (2019).

    Article  PubMed  Google Scholar 

  61. Chuong, K. H. et al. Navigating social and ethical challenges of biobanking for human microbiome research. BMC Med. Ethics 18, 1 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Franzosa, E. A. et al. Identifying personal microbiomes using metagenomic codes. Proc. Natl Acad. Sci. USA 112, E2930–E2938 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Turnbaugh, P. J. Making millennial medicine more meta. mSystems https://doi.org/10.1128/mSystems.00154-17 (2018).

  64. Kelly, C. R., Kim, A. M., Laine, L. & Wu, G. D. The AGA’s Fecal Microbiota Transplantation National Registry: an important step toward understanding risks and benefits of microbiota therapeutics. Gastroenterology 152, 681–684 (2017).

    Article  PubMed  Google Scholar 

  65. Kelly, B. J. et al. Power and sample-size estimation for microbiome studies using pairwise distances and PERMANOVA. Bioinformatics 31, 2461–2468 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Song, S. J. et al. Preservation methods differ in fecal microbiome stability, affecting suitability for field studies. mSystems https://doi.org/10.1128/mSystems.00021-16 (2016).

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Acknowledgements

We thank the Harvard Chan School administration for their support of the Microbiome in Public Health Center. This work was supported in part by NIH NIDDK R24DK110499 (W.S.G. and C.H.) and by the Cancer Research UK Grand Challenge Initiative C10674/A27140 (W.S.G.).

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Correspondence to Wendy S. Garrett or Curtis Huttenhower.

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C.H. is a scientific advisor for Seres Therapeutics, Empress Therapeutics and ZOE Nutrition. W.S.G. is a scientific advisor for Senda Therapeutics, Leap Therapeutics, Evelo Biosciences, Tenza Inc. and SanaRx.

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Wilkinson, J.E., Franzosa, E.A., Everett, C. et al. A framework for microbiome science in public health. Nat Med 27, 766–774 (2021). https://doi.org/10.1038/s41591-021-01258-0

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