Dietary Therapy to Improve Nutrition and Gut Health in Paediatric Crohn’s Disease; A Feasibility Study
, Lucy Bray 4, Angela Allen 1, Emma Jones 2, Britta Urban 1, Sarah Moule 5, Duolao Wang 1 and Raymond J. Playford 6,7
Round 1
Reviewer 1 Report
The design of the current study is reasonable, and the topic is of interest to the field. Some information is essential to revisit before concluding:
1. Gender differences in pediatric IBD patients were recognized previously by other studies. The author should consider performing statistical analysis for the gender-specific differences.
2. The nutrition facts tables of the Bovine colostrum and Placebo milk and the daily milk consumption should be provided in the manuscript.
3. Are subjects receiving other nutrition (i.e., food, drink, or dietary supplement) in addition to the assigned colostrum or milk? The authors should clarify it when describing the study design.
Author Response
The design of the current study is reasonable, and the topic is of interest to the field. Some information is essential to revisit before concluding:
- Gender differences in pediatric IBD patients were recognized previously by other studies. The author should consider performing statistical analysis for the gender-specific differences.
Response: Many thanks for this comment. We agree that gender-specific differences occur in paediatric IBD and may have occurred in our study. However, we have not undertaken subgroup analyses, including by gender, because of the small number of participants. This would certainly be relevant in a larger trial.
- The nutrition facts tables of the Bovine colostrum and Placebo milk and the daily milk consumption should be provided in the manuscript.
Response: Nutritional composition has been described as follows:
“The interventions were either daily BC or a comparator milk. As a natural product, the composition of BC varies but is typically composed of 20% fat, 18% lactose and 55% protein (16% immunoglobulin) with energy value 460kCal/100g. A detailed subcomponent analyses of colostrum is provided in the review of BC constituents.12 The placebo had a similar nutritional profile and was comprised of a mixture of milk powder (70%; Nestle Nido Instant Full Cream Milk Powder, Nestle) and milk protein concentrate (30%; Pure Milk Protein Concentrate 85, Bodybuilding Warehouse, Manchester, UK).” Lines 90-96.
We have reported the milk consumption in the results (lines 186-8; table S1).
- Are subjects receiving other nutrition (i.e., food, drink, or dietary supplement) in addition to the assigned colostrum or milk? The authors should clarify it when describing the study design.
Response: Many thanks for highlighting this omission. We have added the sentence to the methods section: “The interventions were given alongside the young person’s usual diet but no other dietary supplements were provided: (lines 104-5).
Reviewer 2 Report
Congratulations on the research carried out.
The main question addressed by the research [Evaluating the acceptability of Bovine colostrum BC in pediatric CD and generated pilot data on its effects on disease symptoms, biomarkers of intestinal integrity and inflammation, and quality of life] is relevant and exciting. It is a well-conducted, laborious investigation with restrictive inclusion and exclusion criteria and adds value to what has been published. The methods are very refined. The paper is well-written, straightforward, and easy to read. The conclusions are consistent with the evidence and arguments presented, clearly addressing the main issue posed.
Minor objections include:
#The authors acknowledge the limitation of the small number of patients recruited. It is noteworthy that no mention is made in the statistical analysis of the sample calculation to obtain plausible results.
#To improve the palatability of bovine colostrum, the authors have proposed various methods, including sweetening with honey, a nutrient with a high fructose content (35g per 100g) that increases the risk of producing gastrointestinal symptoms such as flatulence and even diarrhea, which can influence acceptability and, in some cases, alter some items of health-related quality of life.
#The study included 2/3 of patients in clinical remission and 1/3 with mild-moderate activity. This criterion seems acceptable, but the small sample size adds difficulty to interpreting the results.
The authors should consider these aspects in the discussion.
Author Response
The main question addressed by the research [Evaluating the acceptability of Bovine colostrum BC in pediatric CD and generated pilot data on its effects on disease symptoms, biomarkers of intestinal integrity and inflammation, and quality of life] is relevant and exciting. It is a well-conducted, laborious investigation with restrictive inclusion and exclusion criteria and adds value to what has been published. The methods are very refined. The paper is well-written, straightforward, and easy to read. The conclusions are consistent with the evidence and arguments presented, clearly addressing the main issue posed.
Minor objections include:
#The authors acknowledge the limitation of the small number of patients recruited. It is noteworthy that no mention is made in the statistical analysis of the sample calculation to obtain plausible results.
Response: We did not undertake a formal sample size calculation for this feasibility study but considered that a total of 50 CYP would be sufficient to evaluate acceptability and also provide preliminary data for future sample size calculations.
#To improve the palatability of bovine colostrum, the authors have proposed various methods, including sweetening with honey, a nutrient with a high fructose content (35g per 100g) that increases the risk of producing gastrointestinal symptoms such as flatulence and even diarrhea, which can influence acceptability and, in some cases, alter some items of health-related quality of life.
Response. We agree with this concern and have added the sentences to the discussion “Although CYP continued their usual diet during the study, a concern is the potential adverse effects of additives to improve the palatability of BC. These include high fructose containing foods, such as honey, as a high fructose diet had a pro-colitic effect in a mouse model of inflammatory bowel disease.28 This should be considered in future trials.” Lines 313-6.
The following reference has been added: 28. Montrose DC, Nishiguchi R, Basu S, Staab HA, Zhou XK, Wang H, Meng L, Johncilla M, Cubillos-Ruiz JR, Morales DK, Wells MT, Simpson KW, Zhang S, Dogan B, Jiao C, Fei Z, Oka A, Herzog JW, Sartor RB, Dannenberg AJ. Dietary Fructose Alters the Composition, Localization, and Metabolism of Gut Microbiota in Association With Worsening Colitis. Cell Mol Gastroenterol Hepatol. 2021;11(2):525-550. doi: 10.1016/j.jcmgh.2020.09.008.
#The study included 2/3 of patients in clinical remission and 1/3 with mild-moderate activity. This criterion seems acceptable, but the small sample size adds difficulty to interpreting the results.
The authors should consider these aspects in the discussion.
Response: We agree with this comment and have already highlighted this in the discussion: “Although the small number of CYP recruited impaired our ability to assess the efficacy of BC,…” line 324.
Reviewer 3 Report
This is an innovative and preliminary study on the beneficial effect of a colostrum-based diet on CD.
Well-structured study, with methodology relevant to what is proposed, and tracing results and discussion based on the findings obtained by the study.
Thus, the author provided the reader, exactly what was proposed in the title, a preliminary and feasibility study, without further elaboration.
Author Response
We thank the reviewer for his/her psotiive comments.
