ena-STUDY-UCSF-03-08-2019-23:11:12:215-193
A Single Fecal Microbial Transplantation Alters Viable Mucosa-associated Microbiota and Reduces Mucosal Inflammation in Clinically-responsive Ulcerative Colitis Patients.
Background Gut microbiome perturbation, characterized by loss of microbial species and their encoded genomic functions, is characteristic of patients with ulcerative colitis (UC) and considered a key contributor to chronic immune activation in this patient population. Fecal microbial transplant (FMT) represents an approach to restore depleted microbiomes and promote immune homeostasis in UC patients. Methods Eighteen UC patients were assigned to one of two study arms: a pre-FMT antimicrobial (rifaximin) or no antimicrobial treatment prior to receipt of a single, pre-screened FMT donor suspension via colonoscopy. Clinical response was defined as =3 point decrease in Mayo score. Peripheral blood and stool samples were collected to evaluate markers of inflammation, and paired colonic biopsies were evaluated for histological response, host gene expression, and transcriptionally active mucosa-associated microbiota pre- and post-FMT. Results Delivery of a single colonoscopic FMT effectively reduced clinical symptoms in one third of ulcerative colitis patients, irrespective of antimicrobial pre-treatment; antimicrobial pre-treatment did not significantly increase the likelihood of clinical response [Relative risk: 1.25 (0.61, 2.25)]. Clinical response was independent of evidence for microbiota engraftment based on fecal samples. Mucosal gene expression of Toll-like receptors (TLR1 and 9) and inflammatory markers (IL6, IL8, IFN?, TGF?) decreased significantly in clinical responders; occludin and IRF3 (a regulator of type I interferon) gene expression increased in these patients. Transcriptionally active mucosa-associated Prevotella, Ruminococcaceae, Faecalibacterium and Eggerthella positively associated with markers of mucosal inflammation, while specific Bacteroides and Dorea correlated with less inflammation. Conclusions Antimicrobial pre-treatment did not increase single dose FMT efficacy in UC patients. Clinical response was not associated with engraftment of donor microbiota, but rather related to enrichment of specific bacteria both in the feces and on the colonic mucosa. Specific, transcriptionally active mucosa-associated bacteria correlated with immune markers of active and resolved disease.
Background Gut microbiome perturbation, characterized by loss of microbial species and their encoded genomic functions, is characteristic of patients with ulcerative colitis (UC) and considered a key contributor to chronic immune activation in this patient population. Fecal microbial transplant (FMT) represents an approach to restore depleted microbiomes and promote immune homeostasis in UC patients. Methods Eighteen UC patients were assigned to one of two study arms: a pre-FMT antimicrobial (rifaximin) or no antimicrobial treatment prior to receipt of a single, pre-screened FMT donor suspension via colonoscopy. Clinical response was defined as =3 point decrease in Mayo score. Peripheral blood and stool samples were collected to evaluate markers of inflammation, and paired colonic biopsies were evaluated for histological response, host gene expression, and transcriptionally active mucosa-associated microbiota pre- and post-FMT. Results Delivery of a single colonoscopic FMT effectively reduced clinical symptoms in one third of ulcerative colitis patients, irrespective of antimicrobial pre-treatment; antimicrobial pre-treatment did not significantly increase the likelihood of clinical response [Relative risk: 1.25 (0.61, 2.25)]. Clinical response was independent of evidence for microbiota engraftment based on fecal samples. Mucosal gene expression of Toll-like receptors (TLR1 and 9) and inflammatory markers (IL6, IL8, IFN?, TGF?) decreased significantly in clinical responders; occludin and IRF3 (a regulator of type I interferon) gene expression increased in these patients. Transcriptionally active mucosa-associated Prevotella, Ruminococcaceae, Faecalibacterium and Eggerthella positively associated with markers of mucosal inflammation, while specific Bacteroides and Dorea correlated with less inflammation. Conclusions Antimicrobial pre-treatment did not increase single dose FMT efficacy in UC patients. Clinical response was not associated with engraftment of donor microbiota, but rather related to enrichment of specific bacteria both in the feces and on the colonic mucosa. Specific, transcriptionally active mucosa-associated bacteria correlated with immune markers of active and resolved disease.