Alexander Khoruts, MD
Professor of Medicine, Division of Gastroenterology Hepatology and Nutrition
Professor of Medicine, Division of Gastroenterology Hepatology and Nutrition
Medical School, University of Minnesota, Minneapolis, MN
Residency, University of Minnesota, Minneapolis, MN
Fellowship, University of Minnesota, Minneapolis, MN
Awards & Recognition
Gut microbiota (commensal microbial communities) is integral to the function of the digestive system and entire body physiology. Disruption of gut microbiota by antibiotics can make the body vulnerable to infections like Clostridium difficile. In addition, gut microbiota likely plays important roles in inflammatory bowel disease, development of the immune system, disorders of energy metabolism like diabetes, and gastrointestinal cancer.
Dr. Khoruts is the Medical Director of the University of Minnesota Microbiota Therapeutics Program. This program brings together multiple investigators from across the Medical School and the University. The primary clinical function at this time is treatment of patients with refractory C. difficile infection. However, additional investigational work is ongoing in metabolic syndrome, gastrointestinal malignancies in cystic fibrosis, blood and marrow transplantation, and inflammatory bowel disease.
Microbiota-host interactions in health and disease
Intestinal microbiota is integral to mammalian physiology and plays important roles in the development and maintenance of the immune system, energy metabolism, and even nervous system function. Over the course of the past century the human population in the Western countries has experienced exposure to antibiotics, markedly altered diet, and increasingly aseptic environment and lifestyle. The full extent of the impact these changes have had on the composition and functionality is yet unknown, but they are hypothesized to have contributed to the emergence of many modern day problems such as autoimmunity, obesity, diabetes, autism, and many others. It is notable that similar disease trends are now apparent in the developing world and newly industrialized nations.
One major consequence of antibiotic pressure experienced by host microbiota is emergence of antibiotic-resistant pathogens. This represents a growing tsunami-like threat to our health care system. Over the past decade we have focused on one such pathogen, Clostridium difficile. Infection with C. difficile commonly cannot be eradicated with standard antibiotics. Our multi-disciplinary team has been one of the world leaders in development in approaches to normalize the intestinal microbial community structure by implanting donor microbiota into patients. This therapeutic approach continues to be central to many of our research projects, which investigate and develop:
- Next generation microbiota therapeutics
- Mechanisms for how restoration microbiota therapies impact disease pathogenesis
- The role of secondary bile acid metabolism in the pathogenesis of C. difficileinfection and development of therapeutic bile acid derivative drugs
- Mechanisms of host-microbiota interactions in energy metabolism
- Microbiota-based therapeutics for inflammatory bowel disease
The fundamental philosophical principles of the laboratory include: (1) multi-disciplinary team science is essential for tackling real life problems; (2) while in vitro and animal models can be critical in research, ultimately we need to do interventional clinical trials in human patients.
- Khoruts, A., Dicksved, J., Jansson, J.K., and M.K. Sadowsky. 2010. Changes in the Composition of the Human Fecal Microbiome after Bacteriotherapy for Recurrent Clostridium Difficile-associated Diarrhea. J. Clin. Gastroenterol. 17:335-342.
- Khoruts, A., and M.J. Sadowsky. 2011. Therapeutic transplantation of the distal gut microbiota. Mucosal Immunol. 4:4-7.
- Bakken, J.S., T. Borody, L.J. Brandt, J.V. Brill, D.C. Demarco, M.A. Franzos, C. Kelly, A. Khoruts, T. Louie, L.P. Martinelli, T.A. Moore, G. Russell, C. Surawicz (The Fecal Microbiota Transplantation Workgroup). 2011. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin. Gastroenterol. Hepatol. 9:1044-1049.
- Borody, T.J., and A. Khoruts. 2011. Fecal microbiota transplantation and emerging applications. Nat. Rev. Gastroenterol. Hepatol. 9:88-96.
- Hamilton, M.J., A.R. Weingarden, M.K. Sadowsky*, and A. Khoruts*. 2012. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. 107:761-767. *Authors equal contributors.
- Hamilton, M.J., A.R. Weingarden, T. Unno, A. Khoruts*, and M.K. Sadowsky*. 2013. High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria. Gut microbes. 4:125-135.
- Weingarden, A.R., Hamilton, M.J., Sadowsky, M.J.*, and Khoruts, A.* 2013. Resolution of Severe Clostridium difficile Infection Following Sequential Fecal Microbiota Transplantation. J. Clin. Gastroenterol. *Authors equally contributed.
- Billings, J.L., Dunitz, J.M., McAllister, S., Herzog, T., Bobr, A., and Khoruts, A. 2013. Early Colon Screening of Adult Patients with Cystic Fibrosis Reveals High Incidence of Adenomatous Colon Polyps. J. Clin. Gastroenterol.
- Kelly, C.R., Kunde, S.S., and Khoruts, A. 2013. A How to Guide: Investigational New Drug Application for Fecal Microbiota Transplantation. Clin Gastroenterol Hepatol.
- Weingarden, A.R., Chen, C., Bobr, A., Yao, D., Lu, Y., Nelson, V.M., Sadowsky, M.J.*, and Khoruts, A.* 2014. Microbiota Transplantation Restores Normal Fecal Bile Acid Composition in Recurrent Clostridium difficile Infection. Am J Physiol Gastointestin Liver Physiol. 306:G310-319. *Authors contributed equally.
- Khoruts, A. Faecal microbiota transplantation 2014: Developing human gut microbiota as a class of therapeutics. Nat. Rev. Gastroenterol. Hepatol. 11:79-80.
- Petrof, E.O. and Khoruts, A. 2014. From stool transplants to next-generation microbiota therapeutics. Gastroenterology, 146:1573-1582.
- Shankar, V., Hamilton, M.J., Khoruts, A., Kilburn, A., Unno, T., Paliy, O., and Sadowsky, M.J. 2014. Species and genus level resolution analysis of microbiota in Clostridium difficile patients following fecal microbiota transplantation. Microbiome.
- Khoruts, A., and Weingarden, A.R. 2014. Emergence of fecal microbiota transplantation as an approach to repair disrupted microbial gut ecology. Immunol. Lett.
- Staley C, Kaiser T, Beura LK, Hamilton MJ, Weingarden AR, Bobr A, Kang J, Masopust D, Sadowsky MJ, Khoruts A. Stable engraftment of human microbiota into mice with a single oral gavage following antibiotic conditioning. Microbiome. 2017 Aug 1;5(1):87.
- Stoltz KL, Erickson R, Staley C, Weingarden AR, Romens E, Steer CJ, KhorutsA, Sadowsky MJ, Dosa PI. Synthesis and Biological Evaluation of Bile Acid Analogues Inhibitory to Clostridium difficile Spore Germination. J Med Chem.2017 Apr 27;60(8):3451-3471
- Staley C, Hamilton MJ, Vaughn BP, Graiziger CT, Newman KM, Kabage AJ, Sadowsky MJ, Khoruts A. Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study. Am J Gastroenterol. 2017 Jun;112(6):940-947
- Khoruts A, Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol. 2016 Sep;13(9):508-16.
University of Minnesota Medical Center
- American Board of Internal Medicine
- American Board of Internal Medicine - Gastroenterology
Gastroenterology; Immune disorders involving the gastrointestinal tract; Microbiota therapeutics