Healthy Siblings of Children With Crohn's Disease Exhibit More Rapid Changes in Microbiota Composition as a Response to Exclusive Enteral Nutrition

Abstract

Background The aim of this study was to determine the impact of exclusive enteral nutrition (EEN) on the microbiota composition of the newly diagnosed Crohn's disease (CD) patients and to determine the effect of EEN received for 2 days in siblings of patients with CD. Methods Newly diagnosed pediatric CD patients (n = 17) and unaffected healthy siblings (n = 10) participated in the study. In CD patients, stool samples were collected at 3 time points: prior to therapy introduction, the second day of EEN therapy, and the last day of EEN therapy. In healthy siblings, stool samples were collected before the introduction of EEN and the second day of EEN. Molecular approach targeting 16S ribosomal RNA was used for analyzing the gut microbiota of participants’ stool samples. Results There was no significant difference in microbial diversity between children with CD and healthy siblings before EEN (P = .127 for HhaI digestion; P = .604 for MspI digestion) as opposed to the second day of EEN (P = .006 HhaI digestion; P = .023 MspI digestion). In healthy controls, significant changes in microbiota composition were apparent by the second day of EEN, contrary to children with CD, in whom similar changes in microbiota composition were apparent on the last day of EEN. Conclusion EEN leads to significant microbiota changes in both healthy children and children with CD. Changes in microbiota composition occur more rapidly in healthy children, whereas in children with CD, significant changes were detected at the end of EEN.

Gut Microbiota Composition Changes following Discontinuation of Exclusive Enteral Nutrition in Children with Crohn’s Disease

“…We previously showed that significant changes in microbial communities already occur on the second day of EEN and continue until the last day of EEN [ 7 ]. That effect was also described by others [ 2 , 5 ], yet only a limited number of studies have performed a follow-up after a return to the free diet, and most commonly only at one time point [ 8 , 11 , 12 , 14 , 17 , 18 ].…”

“…A molecular approach targeting 16S ribosomal RNA was used for analysing the gut microbiota. Microbiota analysis procedures were performed using PCR amplification and terminal restriction fragment length polymorphism (T-RFLP), previously described in detail in Sila et al (2021) [ 7 ].…”

“…EEN is used as a first-line therapy in the treatment of CD in paediatric patients [ 6 ]. The mechanism of action of EEN is not completely understood; however, multiple studies have demonstrated that EEN causes changes in the microbiota of paediatric patients with CD [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Alterations to the microbiota imposed by EEN are, therefore, assumed to be related to its effectiveness in remission induction.…”

“…We previously investigated the effect of EEN on microbiota composition in newly diagnosed, treatment-naïve paediatric CD patients at the following instances: before the introduction of EEN, on the second day of EEN, and at the end of EEN [ 7 ]. We found that EEN causes significant changes in the microbiota, both in CD patients and in their healthy siblings.…”

Review article: Mechanisms underlying the effectiveness of exclusive enteral nutrition in Crohn's disease

“…Understanding how EEN might affect the intestine in a less confounded human situation, such as in healthy subjects, might offer important clues. Such an approach, however, has been seldom taken and is limited to the impact of EEN on the faecal microbiota and their metabolites 58,128,129 . Indeed, EEN reduced bacterial density in healthy subjects, 58 which, as outlined above, was not observed in one of two studies of patients with CD.…”