Microbiome changes associated with sustained eradication of Clostridium difficile after single faecal microbiota transplantation in children with and without inflammatory bowel disease

Abstract

Summary Background Little data are available regarding the effectiveness and associated microbiome changes of faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in children, especially in those with inflammatory bowel disease (IBD) with presumed underlying dysbiosis. Aim To investigate C. difficile eradication and microbiome changes with FMT in children with and without IBD. Methods Children with a history of recurrent CDI (≥3 recurrences) underwent FMT via colonoscopy. Stool samples were collected pre‐FMT and post‐FMT at 2–10 weeks, 10–20 weeks and 6 months. The v4 hypervariable region of the 16S rRNA gene was sequenced. C. difficile toxin B gene polymerase chain reaction was performed. Results Eight children underwent FMT for CDI; five had IBD. All had resolution of CDI symptoms. All tested had eradication of C. difficile at 10–20 weeks and 6 months post‐FMT. Pre‐FMT patient samples had significantly decreased bacterial richness compared with donors (P = 0.01), in those with IBD (P = 0.02) and without IBD (P = 0.01). Post‐FMT, bacterial diversity in patients increased. Six months post‐FMT, there was no significant difference between bacterial diversity of donors and patients without IBD; however, bacterial diversity in those with IBD returned to pre‐FMT baseline. Microbiome composition at 6 months in IBD‐negative patients more closely approximated donor composition compared to IBD‐positive patients. Conclusions FMT gives sustained C. difficile eradication in children with and without IBD. FMT‐restored diversity is sustained in children without IBD. In those with IBD, bacterial diversity returns to pre‐FMT baseline by 6 months, suggesting IBD host‐related mechanisms modify faecal microbiome diversity.

Involvement of Reduced Microbial Diversity in Inflammatory Bowel Disease

“…To investigate the eradication of C. difficile and changes in the microbiome following FMT in children with and without IBD, 8 children (5 with IBD and 3 without IBD) with a history of recurrent CDI (≥3 recurrences) received FMT via colonoscopy. All 8 children showed the resolution of CDI symptoms and eradication of C. difficile at 10–20 weeks and 6 months after the administration of FMT [41]. There was also an increase in the intestinal microbial diversity after FMT therapy [41].…”

“…All 8 children showed the resolution of CDI symptoms and eradication of C. difficile at 10–20 weeks and 6 months after the administration of FMT [41]. There was also an increase in the intestinal microbial diversity after FMT therapy [41]. Three systematic reviews and a meta-analysis on CDI treated with FMT showed an average curative rate of approximately 90% [42–44].…”

Transmission and clearance of potential procarcinogenic bacteria during fecal microbiota transplantation for recurrent Clostridioides difficile

“…Both durable transmission and clearance of procarcinogenic bacteria occurred following FMT, suggesting that additional studies on appropriate screening measures for FMT donors and the long-term consequences and/or benefits of FMT are warranted. cohorts, including a multicenter cohort of 335 children (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Given its successes in rCDI, FMT is being increasingly explored as a therapeutic option for a number of gastrointestinal disorders, as well as other conditions associated with microbial dysbiosis, with recent promising results in clinical trials in ulcerative colitis (UC) (17)(18)(19) and immune checkpoint inhibitor-associated colitis in cancer patients (20).…”

Fecal microbial transplant for the treatment of pediatric inflammatory bowel disease

“…This is partly due to the significantly lower incidence of C. difficile colitis in the pediatric age group[21]. However, small case series have shown similar treatment success of FMT in pediatric RCDI as adults, with rates of remission between 89%-100% in children[22] (Table 2). …”

“…At 6 mo post FMT, microbiota profiles of patients with IBD returned closer to their pre-FMT baseline composition while those patients without IBD retained similarity to FMT donor stool. This suggests the IBD microbiome may involve a dysbiosis that is more resistant to change than the microbiome of an otherwise healthy individual[22]. …”