Safety Of Fecal Microbiota Transplantation In Children And The Clinical Efficacy And Fecal Bile Acid Changes In Pediatric Recurrent Clostridium Difficile Infection Treated With Fecal Microbiota Transplantation

【Aim】 To evaluate the safety of fecal microbiota transplantation(FMT)and to investigate the clinical efficacy and fecal bile acid pattern of pediatric recurrent clostridium difficile infections(RCDI)treated with FMT.【Methods】(1)Fifty-seven pediatric patients who underwent FMT in our hospital from October 2013 to September 2018 were recruited and followed up.The safety of FMT was evaluated through adverse events.(2)Stool sample from 14 RCDI patients were collected for fecal bile acids measure.Clinical efficacy and fecal bile acid changes in pediatric RCDI treated with FMT were analyzed.【Results】(1)Safety of FMT in children: FMT was well tolerated in children with only few self-limited short-term adverse events,which are common in abdominal pain,diarrhea,fever and vomiting.No related long-term adverse events happened.Immunocompromised patients are more likely to have adverse events.(2)Clinical efficacy and fecal bile acid changes in pediatric RCDI treated with FMT: FMT can significantly improve the clinical symptoms of RCDI patients.It would be necessary to accept multiple FMT treatment for some RCDI patients.After FMT,DCA,CA,ACA,7-keto LCA and 3-DHCA were significantly decreased.【Conclusion】 FMT is safe and tolerable for pediatric patients and can significantly improve the clinical symptoms of pediatric RCDI.The changes of fecal bile acid may be related to FMT clinical efficacy.Part 1 Safety of fecal microbiota transplantation in children【Aim】 To investigate the safety of FMT in children.【Content】 A retrospective study was conducted on 57 patients who underwent FMT in our hospital until September 2018.For all 126 times of FMT were followed uniform standards.Adverse events(AEs)related to FMT were divided into short-term AEs(48h post-FMT)and long-term(3 months).All the potential influencing factors AEs,such as age,gender,time of FMT infusion,route of administration,disease type,immune function state and donor genetic background were analyzed in order to further development for FMT in pediatric practice.【Methods】 The clinical information of all the patients and donors were collected.The influence factors were analyzed by chi-square test or rank sum test.Hierarchical chi-square test was used to correct confounding factors and calculate the risk rate of the significant influence factors.【Results】 Fifty-seven patients(mean age 69.6 months,range 4 to 193 months)were recruited.Their average follow-up time after the first FMT was 28.4 months.The most common short-term AEs were abdominal pain,diarrhea,fever and vomiting,all of which were self-limited and symptom-free within 48 h.Two patients had severe AEs.One patient died in the fourth week post-FMT,which considered unrelated to FMT.Among all the influence factors,elder age(P=0.027)and immune function(P=0.003)are more likely to have adverse events.Considering age as a confounding factor,immune function cannot be regarded as independent risk factor for AEs(P=0.061).【Conclusion】 Although children are well tolerated to FMT treatment,pediatrician need to be more cautious for using FMT to those immunocompromised patients.The long-term follow-up observation for the child cohort is required and the effects of FMT on children is still unpredictable.Part 2 Clinical efficacy and fecal bile acid changes in pediatric recurrent clostridium difficile infection treated with fecal microbiota transplantation【Aim】 The clinical efficacy of FMT for treating pediatric recurrent clostridium difficile infection(RCDI)and fecal bile acids changes were analyzed retrospectively.【Content】 The clinical manifestations,AEs and efficacy evaluation of children with RCDI who underwent FMT were analyzed retrospectively.The effects of FMT for changing fecal bile acid metabolism in RCDI children were compared and analyzed between pre and after FMT.【Methods】 All the clinical information of RCDI patients who underwent FMT were collected.The fecal samples were collected before and after FMT and well saved until experiment.The changes in fecal bile acid concentration were measured by UPLC-MS/MS.The differences in bile acid spectra between pre-FMT and post-FMT were analyzed by OPLS-DA,and the changes in different bile acids were compared by t test or Mann-Whitney rank sum test.【Results】 Fourteen RCDI patients,mean aged 53.9 months(12-149 months)had clinical symptoms priority with diarrhea,blood stool,abdominal distension and abdominal pain.After accepting FMT,13 patients’ symptoms improved obviously such as abdominal pain mitigated,frequency of diarrhea decreased,blood stool disappeared and pseudo membrane disappeared.One case got mild symptom remission with blood still existed.Some of patients had symptoms onset in 48 h after FMT.There were 4 AEs occurred for fever,diarrhea,abdominal pain and vomiting respectively.The bile acid spectrum of RCDI patients showed highly difference,which got much approached after FMT and distinct from pre-FMT in OPLS-DA.By comparing the changes of different bile acids,it was found that CDCA,CA,ACA,7-keto LCA and 3-DHCA decreased significantly after FMT(P<0.05),and CDCA decreased the most significantly(P=0.01).【Conclusion】 FMT can significantly improve the clinical symptoms of children with RCDI.However,some children may need multiple FMT treatments.The cure rate of single FMT(14.3%)was lower than multiple FMT(100%).The bile acid spectrum of RCDI children was obvious changed after FMT and CDCA decreased the most significantly(P=0.01),which may be related to the patients’ clinical efficacy.