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The promise of the gut microbiome as part of individualized treatment strategies

Abstract

Variability in disease presentation, progression and treatment response has been a central challenge in medicine. Although variability in host factors and genetics are important, it has become evident that the gut microbiome, with its vast genetic and metabolic diversity, must be considered in moving towards individualized treatment. In this Review, we discuss six broad disease groups: infectious disease, cancer, metabolic disease, cardiovascular disease, autoimmune or inflammatory disease, and allergic and atopic diseases. We highlight current knowledge on the gut microbiome in disease pathogenesis and prognosis, efficacy, and treatment-related adverse events and its promise for stratifying existing treatments and as a source of novel therapies. The Review is not meant to be comprehensive for each disease state but rather highlights the potential implications of the microbiome as a tool to individualize treatment strategies in clinical practice. Although early, the outlook is optimistic but challenges need to be overcome before clinical implementation, including improved understanding of underlying mechanisms, longitudinal studies with multiple data layers reflecting gut microbiome and host response, standardized approaches to testing and reporting, and validation in larger cohorts. Given progress in the microbiome field with concurrent basic and clinical studies, the microbiome will likely become an integral part of clinical care within the next decade.

Key points

  • The gut microbiome, with substantially greater genetic diversity than the host, is an important factor in determining the variability in disease development, progression and treatment response.

  • Tremendous progress has been made in characterizing the microbiome and its influence on biology.

  • Stratifying to species or strain level is important as microorganisms within the same genus might have a differing effect on the same disease process; the same organism might also have different effects on separate disease processes, making the definition of a universal ‘healthy’ microbiota based on composition alone difficult.

  • To incorporate the microbiome in the clinic, large patient cohorts with multidimensional and longitudinal analyses are needed to understand the contribution of the microbiome on disease development, progression and treatment in the context of systems biology.

  • The gut microbiome is an important component in personalized medicine; most of the progress has been in metabolic and cardiovascular disorders as well as in cancer therapies.

  • The gut microbiome is influenced by numerous factors (including age, diet and host genetics) and hence serves as a readout for those factors, simplifying the input for machine learning-based models in clinical practice being developed to predict disease outcomes or treatment response.

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Fig. 1: Maturity of the gut microbiome as a precision medicine tool.
Fig. 2: Association between the gut microbiome and medication therapy.
Fig. 3: The gut microbiome as a readout of host variables in prediction models.

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Acknowledgements

The authors thank L. Busby for her secretarial assistance. This work is supported by funding from NIH DK114007, Center for Individualized Medicine and Department of Medicine Mayo Clinic, Rochester, MN, USA.

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D.A.S., R.A.T.M., D.H.V., J.P.A. and P.C.K. researched data for the article, contributed substantially to discussion of the content and wrote the article. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Purna C. Kashyap.

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P.C.K. serves on the advisory board of Novome Biotechnologies and is an ad hoc consultant for Otsuka Pharmaceuticals, Pendulum Therapeutics and IP group. The other authors declare no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks M. Nieuwdorp, O. Pedersen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Schupack, D.A., Mars, R.A.T., Voelker, D.H. et al. The promise of the gut microbiome as part of individualized treatment strategies. Nat Rev Gastroenterol Hepatol (2021). https://doi.org/10.1038/s41575-021-00499-1

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