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Microbiome-based therapeutics

Abstract

Symbiotic microorganisms inhabiting the gastrointestinal tract promote health by decreasing susceptibility to infection and enhancing resistance to a range of diseases. In this Review, we discuss our increasing understanding of the impact of the microbiome on the mammalian host and recent efforts to culture and characterize intestinal symbiotic microorganisms that produce or modify metabolites that impact disease pathology. Manipulation of the intestinal microbiome has great potential to reduce the incidence and/or severity of a wide range of human conditions and diseases, and the biomedical research community now faces the challenge of translating our understanding of the microbiome into beneficial medical therapies. Our increasing understanding of symbiotic microbial species and the application of ecological principles and machine learning are providing exciting opportunities for microbiome-based therapeutics to progress from faecal microbiota transplantation to the administration of precisely defined and clinically validated symbiotic microbial consortia that optimize disease resistance.

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Fig. 1: Classes of microbiome-based therapeutics.
Fig. 2: Major factors in using faecal microbiota transplantation treatment to restore the microbiome.
Fig. 3: Registered clinical trials using faecal microbiota transplantation.
Fig. 4: Generation of symbiotic microbial consortia.

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Acknowledgements

This work was supported by US NIH grants R01 AI095706, P01 CA023766, U01 AI124275, and R01 AI042135 to E.G.P. and the Duchossois Family Institute of the University of Chicago. M.T.S. was supported by a postdoctoral fellowship from the Canadian Institute for Health Research (FRN#152527) and a postdoctoral fellowship from Emerald Foundation Inc.

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The authors contributed equally to all aspects of the article.

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Correspondence to Eric G. Pamer.

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Competing interests

E.G.P. serves on the advisory board of Diversigen, has received speaker honoraria from Bristol Myers Squibb, Celgene, Seres Therapeutics, MedImmune, Novartis and Ferring Pharmaceuticals, is an inventor on patent applications WPO2015179437A1, entitled “Methods and compositions for reducing Clostridium difficile infection”, and WO2017091753A1, entitled “Methods and compositions for reducing vancomycin-resistant enterococci infection or colonization”, and holds patents that receive royalties from Seres Therapeutics Inc. M.T.S. declares no competing interests.

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Glossary

Microbiota restoration

Re-establishment of the diversity, density and beneficial functions of the microbiota following perturbation.

Colonization resistance

Inhibition of exogenous species, including pathogens, by the resident microbiota.

Colitis

Inflammation occurring in the large intestine.

Engraftment

Establishment of a replicating, self-sustaining population of an introduced species or strain in a community.

Alpha diversity

Measure of community diversity within a sample based on taxonomic richness (number of species) and evenness.

Hepatic steatosis

A condition of non-alcoholic fatty liver disease defined by the accumulation of intrahepatic fat to greater than 5% of liver weight.

Bacteroicins

Short ribosomally synthesized antimicrobial peptides produced by bacteria that often target closely related species but are, in general, not harmful to producing bacteria owing to immune mechanisms.

Mucins

A family of large, highly glycosylated proteins secreted at mucosal surfaces. In the intestine, secreted mucins form a protective and selective barrier between epithelial cells and luminal contents.

Checkpoint immunotherapy

Cancer therapy that functions by promoting an antitumour immune response by targeting proteins such as CTLA4 or PD1/PDL1 that normally function to limit immune responses.

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Sorbara, M.T., Pamer, E.G. Microbiome-based therapeutics. Nat Rev Microbiol 20, 365–380 (2022). https://doi.org/10.1038/s41579-021-00667-9

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