Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after fecal microbiota transplant in inflammatory bowel disease

Yanjia Jason Zhang, Gastroenterology/Nutrition, Boston Children's Hospital, 300 Longwood Ave., Boston, MA, USA.
Athos Bousvaros, Gastroenterology/Nutrition, Boston Children's Hospital, 300 Longwood Ave., Boston, MA, USA.
Michael Docktor, Gastroenterology/Nutrition, Boston Children's Hospital, 300 Longwood Ave., Boston, MA, USA.
Abby L. Kaplan, Gastroenterology/Nutrition, Boston Children's Hospital, 300 Longwood Ave., Boston, MA, USA.
Paul A. Rufo, Gastroenterology/Nutrition, Boston Children's Hospital, 300 Longwood Ave., Boston, MA, USA.
McKenzie Leier, Gastroenterology/Nutrition, Boston Children's Hospital, 300 Longwood Ave., Boston, MA, USA.
Madison Weatherly, Gastroenterology/Nutrition, Boston Children's Hospital, 300 Longwood Ave., Boston, MA, USA.
Lori Zimmerman, Gastroenterology/Nutrition, Boston Children's Hospital, 300 Longwood Ave., Boston, MA, USA.
Le Thanh Nguyen, Department of Biological Engineering, Massachusetts Institute of Technology, 21 Ames St., Cambridge, MA, USA.
Brenda Barton, Gastroenterology/Nutrition, Boston Children's Hospital, 300 Longwood Ave., Boston, MA, USA.
George Russell, Gastroenterology/Nutrition, Maine Medical Center, 22 Bramhall St., Portland, ME, USA.

Abstract

Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.