Antibiotic-induced Changes in Microbiota Composition

The intestinal microbiota consists of complex populations of microbes that contribute to nutrient absorption, vitamin production, immune development and resistance to infection.  Antibiotics, while highly effective at treating and preventing infections, can have adverse effects on the intestinal microbiota. We have found that antibiotic-administration can dramatically reduce the density and diversity of bacteria in the intestines of mice (Ubeda et al. Journal of Clinical Investigation, 2010; Buffie et al. Infection and Immunity, 2012).

Figure 1A single dose of clindamycin alters microbiota composition in the ileum and cecum for 28 days following treatment.  Each bar represents the microbiota composition from the indicated tissue and the indicated times. Panels A and B are derived from mice that were not treated with clindamycin and demonstrate typical stability of microbiota composition over time. Panels C and D demonstrate the marked loss of pretreatment bacterial populations following clindamycin administration on day -1, and the subsequent fluctuations in microbiota composition at later time points.  (Buffie et al. 2012  Infection and Immunity).

We have found that patients undergoing allogeneic hematopoietic stem cell transplantation undergo dramatic changes in microbiota composition, some of which correlate with the subsequent development of bloodstream infection (Taur et al. Clinical Infectious Diseases, 2012), and our studies have also demonstrated that loss of microbiota diversity following transplantation is correlated with higher mortality rate (Taur et al.  Blood, 2014).

Ubeda C, Taur Y, Jenq RR, Equinda MJ, Son T, Samstein M, Viale A, Socci ND, van den Brink MR, Kamboj M, Pamer EG. Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J Clin Invest. 2010 Dec 1;120(12):4332-41.

Buffie CG, Jarchum I, Equinda M, Lipuma L, Gobourne A, Viale A, Ubeda-Morant C, Xavier J, Pamer EG. Profound alterations of intestinal microbiota following a single dose of Clindamycin results in sustained susceptibility to C. difficile-induced colitis. Infect Immun. 2012; 80(1):62-73.

Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, Lee YJ, Dubin KA, Socci ND, Viale A, Perales MA, Jenq RR, van den Brink MR, Pamer EG. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2012 Oct;55(7):905-14.

Taur Y, Jenq RR, Perales MA, Littmann ER, Morjaria S, Ling L, No D, Gobourne A, Viale A, Dahi PB, Ponce DM, Barker JN, Giralt S, van den Brink M, Pamer EG. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014 Aug 14; 124(7):1174-82.

Buffie CG, Pamer EG. Microbiota-mediated colonization resistance against intestinal pathogens. Nat Rev Immunol. 2013 Nov; 13(11):790-801.

Caballero S, Pamer EG. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annual Review of Immunology. 2015; 33:227-258.