Fecal Microbiota Transplant in Children With and Without IBD
Fecal Microbiota Transplant in Children With and Without IBD
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.
Clostridium difficile infection (CDI) is the leading cause of nosocomial diarrhoea in the USA and is increasing in prevalence both in adult and paediatric populations. Those with inflammatory bowel disease (IBD) are at increased risk of CDI. Recurrence of CDI can occur in 20–30% after initial infection, with frequency of recurrence increasing further after subsequent infections.
Faecal microbiota transplantation (FMT) is an effective treatment for recurrent CDI as shown in randomised controlled trials. In adults, it has been shown that CDI is associated with a decrease in microbiota diversity that is restored after FMT. In small studies in children, FMT appears to be effective for recurrent CDI. However, little data exist in children regarding FMT-associated microbiome changes with this intervention. Such studies are warranted, as there are known differences in the developing microbiome of children compared with adults. Moreover, children with IBD have an underlying dysbiosis and are disproportionately susceptible to CDI; yet, there are little data regarding whether FMT gives sustained clearance of C. difficile in these patients and the microbiome changes that occur. Thus, the goal of our study was to investigate whether there is sustained C. difficile eradication after FMT for recurrent CDI in children with and without IBD, and to evaluate associated microbiome changes. We hypothesised that FMT would be less effective for sustained eradication of C. difficile in children with IBD given their underlying IBD-associated dysbiosis.
Abstract and Introduction
Abstract
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.
Introduction
Clostridium difficile infection (CDI) is the leading cause of nosocomial diarrhoea in the USA and is increasing in prevalence both in adult and paediatric populations. Those with inflammatory bowel disease (IBD) are at increased risk of CDI. Recurrence of CDI can occur in 20–30% after initial infection, with frequency of recurrence increasing further after subsequent infections.
Faecal microbiota transplantation (FMT) is an effective treatment for recurrent CDI as shown in randomised controlled trials. In adults, it has been shown that CDI is associated with a decrease in microbiota diversity that is restored after FMT. In small studies in children, FMT appears to be effective for recurrent CDI. However, little data exist in children regarding FMT-associated microbiome changes with this intervention. Such studies are warranted, as there are known differences in the developing microbiome of children compared with adults. Moreover, children with IBD have an underlying dysbiosis and are disproportionately susceptible to CDI; yet, there are little data regarding whether FMT gives sustained clearance of C. difficile in these patients and the microbiome changes that occur. Thus, the goal of our study was to investigate whether there is sustained C. difficile eradication after FMT for recurrent CDI in children with and without IBD, and to evaluate associated microbiome changes. We hypothesised that FMT would be less effective for sustained eradication of C. difficile in children with IBD given their underlying IBD-associated dysbiosis.
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