Skip to main content
SpringerLink
Log in

Targeting friend and foe: Emerging therapeutics in the age of gut microbiome and disease

  • Review
  • Human Microbiomes and Probiotics
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Mucosal surfaces that line our gastrointestinal tract are continuously exposed to trillions of bacteria that form a symbiotic relationship and impact host health and disease. It is only beginning to be understood that the cross-talk between the host and microbiome involve dynamic changes in commensal bacterial population, secretion, and absorption of metabolites between the host and microbiome. As emerging evidence implicates dysbiosis of gut microbiota in the pathology and progression of various diseases such as inflammatory bowel disease, obesity, and allergy, conventional treatments that either overlook the microbiome in the mechanism of action, or eliminate vast populations of microbes via wide-spectrum antibiotics need to be reconsidered. It is also becoming clear the microbiome can influence the body’s response to therapeutic treatments for cancers. As such, targeting the microbiome as treatment has garnered much recent attention and excitement from numerous research labs and biotechnology companies. Treatments range from fecal microbial transplantation to precision-guided molecular approaches. Here, we survey recent progress in the development of innovative therapeutics that target the microbiome to treat disease, and highlight key findings in the interplay between host microbes and therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Andremont, A. 2017. Too early to recommend early fecal microbiota transplantation (FMT) in patients with severe Clostridium difficile infections (CDI), or not too early? Clin. Infect. Dis. DOI: 10.1093/cid/cix763 (in press).

    Google Scholar 

  • Aron-Wisnewsky, J. and Clement, K. 2016. The gut microbiome, diet, and links to cardiometabolic and chronic disorders. Nat. Rev. Nephrol. 12, 169–181.

    Article  CAS  PubMed  Google Scholar 

  • Bagdasarian, N., Rao, K., and Malani, P.N. 2015. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA 313, 398–408.

    Article  PubMed  Google Scholar 

  • Belkaid, Y. and Naik, S. 2013. Compartmentalized and systemic control of tissue immunity by commensals. Nat. Immunol. 14, 646–653.

    Article  CAS  PubMed  Google Scholar 

  • Bennet, J.D. and Brinkman, M. 1989. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet 1, 164.

    Article  CAS  PubMed  Google Scholar 

  • Bikard, D. and Barrangou, R. 2017. Using CRISPR-Cas systems as antimicrobials. Curr. Opin. Microbiol. 37, 155–160.

    Article  CAS  PubMed  Google Scholar 

  • Bikard, D., Euler, C.W., Jiang, W., Nussenzweig, P.M., Goldberg, G.W., Duportet, X., Fischetti, V.A., and Marraffini, L.A. 2014. Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials. Nat. Biotechnol. 32, 1146–1150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borody, T.J., Warren, E.F., Leis, S., Surace, R., and Ashman, O. 2003. Treatment of ulcerative colitis using fecal bacteriotherapy. J. Clin. Gastroenterol. 37, 42–47.

    Article  PubMed  Google Scholar 

  • Brown, S.L., Riehl, T.E., Walker, M.R., Geske, M.J., Doherty, J.M., Stenson, W.F., and Stappenbeck, T.S. 2007. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J. Clin. Invest. 117, 258–269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Browne, A.S. and Kelly, C.R. 2017. Fecal transplant in inflammatory bowel disease. Gastroenterol. Clin. North Am. 46, 825–837.

    Article  PubMed  Google Scholar 

  • Colman, R.J. and Rubin, D.T. 2014. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J. Crohns Colitis 8, 1569–1581.

    Article  PubMed  PubMed Central  Google Scholar 

  • DeGruttola, A.K., Low, D., Mizoguchi, A., and Mizoguchi, E. 2016. Current understanding of dysbiosis in disease in human and animal models. Inflamm. Bowel Dis. 22, 1137–1150.

    Article  PubMed  PubMed Central  Google Scholar 

  • Donaldson, G.P., Lee, S.M., and Mazmanian, S.K. 2016. Gut biogeography of the bacterial microbiota. Nat. Rev. Microbiol. 14, 20–32.

    Article  CAS  PubMed  Google Scholar 

  • Dubberke, E.R., Mullane, K.M., Gerding, D.N., Lee, C.H., Louie, T.J., Guthertz, H., and Jones, C. 2016. Clearance of vancomycin-resistant Enterococcus concomitant with administration of a microbiota-based drug targeted at recurrent Clostridium difficile infection. Open Forum Infect. Dis. 3, ofw133.

    Article  PubMed  PubMed Central  Google Scholar 

  • Duncan, S.H., Scott, K.P., Ramsay, A.G., Harmsen, H.J., Welling, G.W., Stewart, C.S., and Flint, H.J. 2003. Effects of alternative dietary substrates on competition between human colonic bacteria in an anaerobic fermentor system. Appl. Environ. Microbiol. 69, 1136–1142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farber, J., Illiger, S., Berger, F., Gartner, B., von Muller, L., Lohmann, C.H., Bauer, K., Grabau, C., Zibolka, S., Schluter, D., et al. 2017. Management of a cluster of Clostridium difficile infections among patients with osteoarticular infections. Antimicrob. Resist. Infect. Control 6, 22.

    Article  PubMed  PubMed Central  Google Scholar 

  • Flint, H.J., Scott, K.P., Duncan, S.H., Louis, P., and Forano, E. 2012. Microbial degradation of complex carbohydrates in the gut. Gut Microbes 3, 289–306.

    Article  PubMed  PubMed Central  Google Scholar 

  • Furusawa, Y., Obata, Y., Fukuda, S., Endo, T.A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. 2013. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450.

    Article  CAS  PubMed  Google Scholar 

  • Ge, P., Scholl, D., Leiman, P.G., Yu, X., Miller, J.F., and Zhou, Z.H. 2015. Atomic structures of a bactericidal contractile nanotube in its pre-and postcontraction states. Nat. Struct. Mol. Biol. 22, 377–382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gebhart, D., Lok, S., Clare, S., Tomas, M., Stares, M., Scholl, D., Donskey, C.J., Lawley, T.D., and Govoni, G.R. 2015. A modified R-type bacteriocin specifically targeting Clostridium difficile prevents colonization of mice without affecting gut microbiota diversity. MBio 6, e02368–14.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gebhart, D., Williams, S.R., Bishop-Lilly, K.A., Govoni, G.R., Willner, K.M., Butani, A., Sozhamannan, S., Martin, D., Fortier, L.C., and Scholl, D. 2012. Novel high-molecular-weight, R-type bacteriocins of Clostridium difficile. J. Bacteriol. 194, 6240–6247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geirnaert, A., Calatayud, M., Grootaert, C., Laukens, D., Devriese, S., Smagghe, G., De Vos, M., Boon, N., and Van de Wiele, T. 2017. Butyrate-producing bacteria supplemented in vitro to Crohn’s disease patient microbiota increased butyrate production and enhanced intestinal epithelial barrier integrity. Sci. Rep. 7, 11450.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gopalakrishnan, V., Spencer, C.N., Nezi, L., Reuben, A., Andrews, M.C., Karpinets, T.V., Prieto, P.A., Vicente, D., Hoffman, K., Wei, S.C., et al. 2018. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103.

    Article  CAS  PubMed  Google Scholar 

  • Guo, L., McLean, J.S., Yang, Y., Eckert, R., Kaplan, C.W., Kyme, P., Sheikh, O., Varnum, B., Lux, R., Shi, W., et al. 2015. Precisionguided antimicrobial peptide as a targeted modulator of human microbial ecology. Proc. Natl. Acad. Sci. USA 112, 7569–7574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haurwitz, R.E., Jinek, M., Wiedenheft, B., Zhou, K., and Doudna, J.A. 2010. Sequence-and structure-specific RNA processing by a CRISPR endonuclease. Science 329, 1355–1358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hemarajata, P. and Versalovic, J. 2013. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap. Adv. Gastroenterol. 6, 39–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelly, C.R., Kahn, S., Kashyap, P., Laine, L., Rubin, D., Atreja, A., Moore, T., and Wu, G. 2015. Update on fecal microbiota transplantation 2015: Indications, methodologies, mechanisms, and outlook. Gastroenterology 149, 223–237.

    Article  PubMed  PubMed Central  Google Scholar 

  • Khanna, S. 2018. Microbiota replacement therapies: Innovation in gastrointestinal care. Clin. Pharmacol. Ther. 103, 102–111.

    Article  CAS  PubMed  Google Scholar 

  • Khanna, S. and Raffals, L.E. 2017. The microbiome in Crohn’s Disease: Role in pathogenesis and role of microbiome replacement therapies. Gastroenterol. Clin. North Am. 46, 481–492.

    Article  PubMed  Google Scholar 

  • Kirk, J.A., Gebhart, D., Buckley, A.M., Lok, S., Scholl, D., Douce, G.R., Govoni, G.R., and Fagan, R.P. 2017. New class of precision antimicrobials redefines role of Clostridium difficile S-layer in virulence and viability. Sci. Transl. Med. 9, eaah6813.

    Article  PubMed  PubMed Central  Google Scholar 

  • Knight, D.R., Elliott, B., Chang, B.J., Perkins, T.T., and Riley, T.V. 2015. Diversity and evolution in the genome of Clostridium difficile. Clin. Microbiol. Rev. 28, 721–741.

    Article  PubMed  PubMed Central  Google Scholar 

  • LeBlanc, J.G., Milani, C., de Giori, G.S., Sesma, F., van Sinderen, D., and Ventura, M. 2013. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr. Opin. Biotechnol. 24, 160–168.

    Article  CAS  PubMed  Google Scholar 

  • Lopez, C.A., Kingsbury, D.D., Velazquez, E.M., and Baumler, A.J. 2014. Collateral damage: microbiota-derived metabolites and immune function in the antibiotic era. Cell Host Microbe 16, 156–163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathewson, N.D., Jenq, R., Mathew, A.V., Koenigsknecht, M., Hanash, A., Toubai, T., Oravecz-Wilson, K., Wu, S.R., Sun, Y., Rossi, C., et al. 2016. Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease. Nat. Immunol. 17, 505–513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matson, V., Fessler, J., Bao, R., Chongsuwat, T., Zha, Y., Alegre, M.L., Luke, J.J., and Gajewski, T.F. 2018. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359, 104–108.

    Article  CAS  PubMed  Google Scholar 

  • Moayyedi, P., Surette, M.G., Kim, P.T., Libertucci, J., Wolfe, M., Onischi, C., Armstrong, D., Marshall, J.K., Kassam, Z., Reinisch, W., et al. 2015. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149, 102–109.e6.

    Article  PubMed  Google Scholar 

  • Neish, A.S. 2009. Microbes in gastrointestinal health and disease. Gastroenterology 136, 65–80.

    Article  PubMed  Google Scholar 

  • Nishida, A., Inoue, R., Inatomi, O., Bamba, S., Naito, Y., and Andoh, A. 2017. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin. J. Gastroenterol. 11, 1–10.

    Article  PubMed  Google Scholar 

  • Paramsothy, S., Kamm, M.A., Kaakoush, N.O., Walsh, A.J., van den Bogaerde, J., Samuel, D., Leong, R.W.L., Connor, S., Ng, W., Paramsothy, R., et al. 2017. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 389, 1218–1228.

    Article  PubMed  Google Scholar 

  • Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., and Medzhitov, R. 2004. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118, 229–241.

    Article  CAS  PubMed  Google Scholar 

  • Rossen, N.G., MacDonald, J.K., de Vries, E.M., D’Haens, G.R., de Vos, W.M., Zoetendal, E.G., and Ponsioen, C.Y. 2015. Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. World J. Gastroenterol. 21, 5359–5371.

    Article  PubMed  PubMed Central  Google Scholar 

  • Round, J.L. and Mazmanian, S.K. 2009. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313–323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Routy, B., Le Chatelier, E., Derosa, L., Duong, C.P.M., Alou, M.T., Daillere, R., Fluckiger, A., Messaoudene, M., Rauber, C., Roberti, M.P., et al. 2018. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97.

    Article  CAS  PubMed  Google Scholar 

  • Schwan, A., Sjolin, S., Trottestam, U., and Aronsson, B. 1983. Relapsing Clostridium difficile enterocolitis cured by rectal infusion of homologous faeces. Lancet 2, 845.

    Article  CAS  PubMed  Google Scholar 

  • Suskind, D.L., Brittnacher, M.J., Wahbeh, G., Shaffer, M.L., Hayden, H.S., Qin, X., Singh, N., Damman, C.J., Hager, K.R., Nielson, H., et al. 2015. Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn’s disease. Inflamm. Bowel Dis. 21, 556–563.

    Article  PubMed  PubMed Central  Google Scholar 

  • Talbot, A.M. 2017. Vedanta biosciences announces initiation of phase 1a/1b trial for new drug class of rationally-defined bacterial consortia derived from the human microbiome. Business Wire. PureTech Health. Available at https://www.businesswire. com/news/home/20171206006422/en/Vedanta-Biosciences-An nounces-Initiation-Phase-1a1b-Trial (accessed December 07, 2017).

    Google Scholar 

  • Vindigni, S.M. and Surawicz, C.M. 2017. Fecal microbiota transplantation. Gastroenterol. Clin. North Am. 46, 171–185.

    Article  PubMed  Google Scholar 

  • Yosef, I., Manor, M., Kiro, R., and Qimron, U. 2015. Temperate and lytic bacteriophages programmed to sensitize and kill antibioticresistant bacteria. Proc. Natl. Acad. Sci. USA 112, 7267–7272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, F., Wen, Y., and Guo, X. 2014. CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum. Mol. Genet. 23, R40–R46.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Food and Nutrition, Chungnam National University, Daejeon, 34134, Republic of Korea

    Jin Ah Cho

  2. Division of Gastroenterology, Boston Children’s Hospital, Boston, 02115, USA

    Daniel J.F. Chinnapen

  3. Department of Pediatrics, Harvard Medical School, Boston, 02115, USA

    Daniel J.F. Chinnapen

  4. Harvard Digestive Diseases Center, Boston, 02115, USA

    Daniel J.F. Chinnapen

Authors
  1. Jin Ah Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel J.F. Chinnapen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel J.F. Chinnapen.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cho, J.A., Chinnapen, D.J. Targeting friend and foe: Emerging therapeutics in the age of gut microbiome and disease. J Microbiol. 56, 183–188 (2018). https://doi.org/10.1007/s12275-018-8037-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-018-8037-z

Keywords

Search

Navigation