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Vol. 89. Num. 3.01 September 2018
Pages 135-190
Vol. 89. Num. 3.01 September 2018
Pages 135-190
Scientific Letter
DOI: 10.1016/j.anpede.2017.10.004
Open Access
Faecal microbiota transplant in a child with very early onset inflammatory bowel disease
Trasplante de microbiota fecal en niño con enfermedad inflamatoria intestinal de inicio muy precoz
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Carlos Sierra Salinasa,b, María Isabel Vicioso Recioc, Javier Blasco-Alonsoa,b, María Juliana Serrano Nietoa, Víctor Manuel Navas-Lópeza,b,
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victor.navas@gmail.com

Corresponding author.
a Unidad de Gastroenterología y Nutrición Infantil, Unidad de Gestión Clínica de Pediatría, Hospital Materno-Infantil, Málaga, Spain
b Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain
c Unidad de Gestión Clínica de Laboratorio, Hospital Materno-Infantil, Málaga, Spain
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Tables (2)
Table 1. Donor screening criteria.
Table 2. Patient progress.
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The intestinal dysbiosis found in patients with inflammatory bowel disease (IBD) has partly guided the development of treatment strategies. Faecal microbiota transplantation (FMT), which consists in the infusion of a faecal suspension from a healthy donor into the gastrointestinal tract of a recipient to cure a specific disease associated with changes in the intestinal microbiota, has proven efficient in the treatment of recurrent infection by Clostridium difficile in adults and children. This treatment modality could also contribute significantly to the control of IBD. Diverting ileostomy is a surgical intervention that has been used as a temporising therapy in children with refractory colitis to stabilise symptoms, improve nutritional status and taper or discontinue steroid therapy.1 We describe the first paediatric case of FMT via diverted ileostomy performed in Spain.

The patient was a boy aged 6 years and 7 months whose mother had Crohn disease. He had received a diagnosis of inflammatory bowel disease unclassified (IBDU) at age 2 years based on a history of recurrent episodes of bloody diarrhoea, anaemia and hypoalbuminaemia. Tests for the differential diagnosis of immunodeficiencies and monogenic inflammatory diseases were negative, and diagnostic tests for detection of infection including tuberculosis and cytomegalovirus were repeatedly negative, except in the assessment of 3 episodes of bloody diarrhoea, when the patient tested positive for C. difficile toxin. Three endoscopic examinations with histological examination of biopsy specimens did not provide significant findings that would allow the diagnostic classification of colitis. The patient did not respond to conventional treatment with mesalamine, systemic steroids, thiopurines and infliximab (with drug level monitoring revealing levels within the normal range for both). With the agreement of the family, the decision was made not to perform a colectomy, opting for the alternative of diverting ileostomy, and scheduling a FMT via the inferior stoma before closure of the ileostomy. The family provided informed consent, and the clinical ethics board of the hospital approved the procedure. Stringent criteria for donor selection were applied with the aim of preventing or reducing the severity of potential donor-related events in the recipient (Table 1).

Table 1.

Donor screening criteria.

Age >18 years 
BMI within normal range 
No personal or family history of autoimmune disease 
No evidence of current transmissible disease 
No evidence of psychiatric disorders 
No use of antibiotic agents or proton pump inhibitors in the past 3 months 
Food diary to verify healthy diet 
Stool cultures negative for pathogenic bacteria, parasites, Clostridium difficile, rotavirus, adenovirus 
Faecal calprotectin <50μg/g of faeces 
Negative for Helicobacter pylori stool antigen 
Negative serologic tests for hepatitis A, B and C, HIV, syphilis and CMV 
Normal blood panel results (complete blood count, creatinine, electrolytes, transaminases, cholesterol, triglycerides, ferritin, albumin, immunoglobulins, CRP and vitamin D3) 
Absence of high-risk sexual behaviour (multiple partners, sex work) 
No history of travel to endemic regions with a high prevalence of diarrheal diseases 

BMI, body mass index; CMV, cytomegalovirus; CRP, C-reactive protein; HIV, human immunodeficiency virus.

The procedure involved the preparation of a suspension of fresh donor faeces, which had been produced 3h prior and stored at room temperature in a sterile container. In the hospital laboratory, a 50g sample of the fresh faeces was blended in 150mL of nonbacteriostatic physiological saline, the slurry filtered, and the resulting suspension collected in a sterile container. A sterile syringe was used to deliver 50mL of the faecal suspension through the inferior stoma of the ileostomy. The patient remained in the supine position for 2h after transplantation. Twenty days later, the patient underwent a second transplantation of faecal matter from the same donor following the same procedure. The patient tolerated the intervention very well. Table 2 describes the progress of the patient after transplantation.

Table 2.

Patient progress.

Hb, g/dL  Platelets, /mm3  CRP, mg/L  Albumin, g/dL  Faecal calprotectin, μg/g  Weight, kg  Height, cm 
Day 0  Diverting ileostomy  7.2  890,000  136  1.9  570  12.500  101.5 
Day 74  74th day of diverting ileostomy  9.5  914,000  70  2.5  130 (ileostomy)  14.800  104.5 
Day 74  1st FMT infusion 
Day 93  2nd FMT infusion 
Day 113  Post-FMT outcome  9.6  565,000  11.6  3.5  115 (ileostomy)  16  105 
Day 113  Ileostomy closure 
Day 127  14 days post-ileostomy closure  9.4  995,000  92.8  2.3  650  14.600  105.5 
Day 163  49 days post-ileostomy closure  8.9  887,000  42.1  2.6  730  14.400  105.5 

CRP, C-reactive protein; FMT, faecal microbiota transplantation; Hb, haemoglobin.

The case presented here is relevant in part due to the performance of diverting ileostomy in a child with severe colitis refractory to treatment, a technique that was recently described by Maxwell et al.1 for treatment of this type of situation. We did observe clinical improvement in our patient, with significant recovery of body weight and a moderate decrease in CRP. Once the patient had stabilised, FMT was performed with the aim of amplifying the benefits of treatment. There is still very little data on the use of FMT in paediatrics, especially for treatment of IBD. On the other hand, there are substantial methodological differences between published studies, which makes it difficult to draw valid conclusions. We are not aware of any previous publication reporting the delivery of the faecal suspension via ileostomy in paediatric patients. Although there is no consensus on the optimal delivery route, the evidence suggests that infusion via colonoscopy is superior to retention enema and the nasogastric and nasoenteric routes, not only because of patient acceptance but also because it achieves infusion of the entire colon.2 In our case, we considered that FMT through the stoma of the ileostomy offered the best possible conditions, as direct delivery of the faecal suspension to the terminal ileum guaranteed the gradual passage through the entire colon. After 2 infusions, there was a very satisfactory improvement of symptoms, probably due to the additive beneficial effects of ileal diversion and FMT. Few paediatric studies have been published on the use of FMT in children with colitis in the context of IBD, and their results are contradictory. In our case, unlike the studies mentioned above,3–6 the suspension was delivered by direct infusion to the distal ileum and not via enema, colonoscopy or nasoenteric tube, as direct infusion probably increases the chances of anterograde deposition of the infusion at the colonic level, avoiding potential interferences during the gastrointestinal transit. Unfortunately, we are unable to present favourable outcome data for our patient. We do not know how many infusions of faecal solution he may have needed. Performance of randomised clinical trials in children is of the essence in order to clarify the numerous doubts we have at present.

References
[1]
E.C. Maxwell,N. Dawany,R.N. Baldassano,P. Mamula,P. Mattei,L. Albenberg
Diverting ileostomy for the treatment of severe, refractory. Pediatric inflammatory bowel disease
J Pediatr Gastroenterol Nutr, 65 (2017), pp. 299-305 http://dx.doi.org/10.1097/MPG.0000000000001498
[2]
L.J. Brandt,O.C. Aroniadis
An overview of fecal microbiota transplantation: techniques, indications, and outcomes
Gastrointest Endosc, 78 (2013), pp. 240-249 http://dx.doi.org/10.1016/j.gie.2013.03.1329
[3]
S. Kunde,A. Pham,S. Bonczyk,T. Crumb,M. Duba,H.J. Conrad
Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis
J Pediatr Gastroenterol Nutr, 56 (2013), pp. 597-601 http://dx.doi.org/10.1097/MPG.0b013e318292fa0d
[4]
D.L. Suskind,N. Singh,H. Nielson,G. Wahbeh
Fecal microbial transplant via nasogastric tube for active pediatric ulcerative colitis
J Pediatr Gastroenterol Nutr, 60 (2015), pp. 27-29 http://dx.doi.org/10.1097/MPG.0000000000000544
[5]
Y. Vandenplas,G. Veereman,J. van der Werff Ten Bosch,A. Goossens,D. Pierard,J.N. Samsom
Fecal microbial transplantation in early-onset colitis: caution advised
J Pediatr Gastroenterol Nutr, 61 (2015), pp. e12-e14 http://dx.doi.org/10.1097/MPG.0000000000000281
[6]
H. Kumagai,K. Yokoyama,T. Imagawa,S. Inoue,J. Tulyeu,M. Tanaka
Failure of fecal microbiota transplantation in a three-year-old child with severe refractory ulcerative colitis
Pediatr Gastroenterol Hepatol Nutr, 19 (2016), pp. 214-220 http://dx.doi.org/10.5223/pghn.2016.19.3.214

Please cite this article as: Sierra Salinas C, Vicioso Recio MI, Blasco-Alonso J, Serrano Nieto MJ, Navas-López VM. Trasplante de microbiota fecal en niño con enfermedad inflamatoria intestinal de inicio muy precoz. An Pediatr (Barc). 2018;89:184–186.

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