Title: Dietary triggers of gut inflammation following exclusive enteral nutrition in children with
Crohn’s disease: a pilot study
Version: 1 Date: 22 Jul 2021
Reviewer's report:
Thanks for the opportunity to review the manuscript “Dietary triggers of gut inflammation
following exclusive enteral nutrition in children with Crohn’s disease: a pilot study”.
This study is interesting and addresses a very important topic to both patients and health care
providers above. I have several comments for the authors to consider while reporting on this
topic.
Regarding nutrient intake, was dietary fibre considered as a homogenous entity, or was this
sub-divided into soluble, insoluble, resistant starch, etc? Each of these fibre sub-types may be
associated with different microbial and clinical consequences.
Furthermore, dietary fiber in both groups is very low, 12 and 10 g respectively. It is really
difficult to draw any clinically meaningful conclusions with this level of low fiber intake
Can the authors provide protein intake on a per kg basis in addition to the current presentation?
I would imagine that children would have variable weights depending on age, and in fact some
of the protein intakes may be quite low on a per kg basis.
In the discussion, please discuss protein in greater detail. Where do vegan sources of protein fit
into the potential adverse role for total proteins? Why did the authors not collect vegan protein
data? If these were collected, they should be presented. While protein intake between the groups
was higher, as discussed above, was there an effort to correct for other factors such as nutritional
status, physical activity, and disease activity?
Please discuss this statement in the discussion further about protein fermentation: “This could
potentially result from adequate intake of dietary fibre in those patients, hence exceeding the
threshold below which excessive protein fermentation occurs in the colon. “Is this correctly
worded? Please discuss the role of fiber adequacy in protecting against protein fermentation,
and supply a reference.
How were macronutrient requirements calculated given these were pediatric patients, and
had active disease during the induction phase? Did RNI consider disease activity? Or were
values used for healthy pediatric groups? How did malnutrition influence energy and protein
requirements?
Were data captured for legumes, resistant starches, dairy, fermented dairy, food additives? Please
discuss whether these factors were considered in the predictive model.
Did the authors attempt to identify food/nutrient factors that may have protective benefits to
relapse (green leafy, oily fish, fruit, B-carotene etc)?
Please comment on protein/energy malnutrition prevalence (SGA, pgSGA, GLIM etc)
“MEN was prescribed to provide 20-25% of daily energy requirements.” Did all patients receive
MEN at baseline to provide 20-25% of energy requirements? Or did some patients receive only
whole food diet?
What MEN formula was used?
While biomarker inflammation is undoubtedly important, patient symptoms are of importance
as well. Were data about symptoms captured after reintroduction?
“None had commenced or were receiving another induction therapy.” Were any patients
receiving maintenance medical therapies?
The methods for fecal starch and gluten immunogenic peptide require description, beyond  a
reference. Please describe the rationale for these readouts. Why were these readouts chosen as
opposed to gut microbiome and/or metabolomic readouts? Did the authors capture fecal bile
acids ?
In the abstract, please provide the units over time period. Was the time unit per day for all
variables?
In conclusions, authors need to be cautious about drawing conclusions about fiber as if it is a
single entity. Authors should attempt to sub-categorize fiber into soluble, insoluble, and resistant
starches..
Figure 2 – Do the green bars indicate protective factors against relapse? The authors should
discuss this in the manuscript
How was processed meat defined? Did the authors distinguish between fresh meat that was
preserved with celery salt for example compared  to smoked meat?
Title: Dietary triggers of gut inflammation following exclusive enteral nutrition in children with
Crohn’s disease: a pilot study
Version: 1 Date: 22 Jul 2021
Reviewer's report:
Thanks for the opportunity to review the manuscript “Dietary triggers of gut inflammation
following exclusive enteral nutrition in children with Crohn’s disease: a pilot study”.
This study is interesting and addresses a very important topic to both patients and health care
providers above. I have several comments for the authors to consider while reporting on this
topic.
Regarding nutrient intake, was dietary fibre considered as a homogenous entity, or was this
sub-divided into soluble, insoluble, resistant starch, etc? Each of these fibre sub-types may be
associated with different microbial and clinical consequences.
Furthermore, dietary fiber in both groups is very low, 12 and 10 g respectively. It is really
difficult to draw any clinically meaningful conclusions with this level of low fiber intake
Can the authors provide protein intake on a per kg basis in addition to the current presentation?
I would imagine that children would have variable weights depending on age, and in fact some
of the protein intakes may be quite low on a per kg basis.
In the discussion, please discuss protein in greater detail. Where do vegan sources of protein fit
into the potential adverse role for total proteins? Why did the authors not collect vegan protein
data? If these were collected, they should be presented. While protein intake between the groups
was higher, as discussed above, was there an effort to correct for other factors such as nutritional
status, physical activity, and disease activity?
Please discuss this statement in the discussion further about protein fermentation: “This could
potentially result from adequate intake of dietary fibre in those patients, hence exceeding the
threshold below which excessive protein fermentation occurs in the colon. “Is this correctly
worded? Please discuss the role of fiber adequacy in protecting against protein fermentation,
and supply a reference.
How were macronutrient requirements calculated given these were pediatric patients, and
had active disease during the induction phase? Did RNI consider disease activity? Or were
values used for healthy pediatric groups? How did malnutrition influence energy and protein
requirements?
Were data captured for legumes, resistant starches, dairy, fermented dairy, food additives? Please
discuss whether these factors were considered in the predictive model.
Did the authors attempt to identify food/nutrient factors that may have protective benefits to
relapse (green leafy, oily fish, fruit, B-carotene etc)?
Please comment on protein/energy malnutrition prevalence (SGA, pgSGA, GLIM etc)
“MEN was prescribed to provide 20-25% of daily energy requirements.” Did all patients receive
MEN at baseline to provide 20-25% of energy requirements? Or did some patients receive only
whole food diet?
What MEN formula was used?
While biomarker inflammation is undoubtedly important, patient symptoms are of importance
as well. Were data about symptoms captured after reintroduction?
“None had commenced or were receiving another induction therapy.” Were any patients
receiving maintenance medical therapies?
The methods for fecal starch and gluten immunogenic peptide require description, beyond  a
reference. Please describe the rationale for these readouts. Why were these readouts chosen as
opposed to gut microbiome and/or metabolomic readouts? Did the authors capture fecal bile
acids ?
In the abstract, please provide the units over time period. Was the time unit per day for all
variables?
In conclusions, authors need to be cautious about drawing conclusions about fiber as if it is a
single entity. Authors should attempt to sub-categorize fiber into soluble, insoluble, and resistant
starches..
Figure 2 – Do the green bars indicate protective factors against relapse? The authors should
discuss this in the manuscript
How was processed meat defined? Did the authors distinguish between fresh meat that was
preserved with celery salt for example compared  to smoked meat?
Please review this paper.
user
Title: Dietary triggers of gut inflammation following exclusive enteral nutrition in children with
Crohn’s disease: a pilot study
Version: 1 Date: 22 Jul 2021
Reviewer's report:
Thanks for the opportunity to review the manuscript “Dietary triggers of gut inflammation
following exclusive enteral nutrition in children with Crohn’s disease: a pilot study”.
This study is interesting and addresses a very important topic to both patients and health care
providers above. I have several comments for the authors to consider while reporting on this
topic.
Regarding nutrient intake, was dietary fibre considered as a homogenous entity, or was this
sub-divided into soluble, insoluble, resistant starch, etc? Each of these fibre sub-types may be
associated with different microbial and clinical consequences.
Furthermore, dietary fiber in both groups is very low, 12 and 10 g respectively. It is really
difficult to draw any clinically meaningful conclusions with this level of low fiber intake
Can the authors provide protein intake on a per kg basis in addition to the current presentation?
I would imagine that children would have variable weights depending on age, and in fact some
of the protein intakes may be quite low on a per kg basis.
In the discussion, please discuss protein in greater detail. Where do vegan sources of protein fit
into the potential adverse role for total proteins? Why did the authors not collect vegan protein
data? If these were collected, they should be presented. While protein intake between the groups
was higher, as discussed above, was there an effort to correct for other factors such as nutritional
status, physical activity, and disease activity?
Please discuss this statement in the discussion further about protein fermentation: “This could
potentially result from adequate intake of dietary fibre in those patients, hence exceeding the
threshold below which excessive protein fermentation occurs in the colon. “Is this correctly
worded? Please discuss the role of fiber adequacy in protecting against protein fermentation,
and supply a reference.
How were macronutrient requirements calculated given these were pediatric patients, and
had active disease during the induction phase? Did RNI consider disease activity? Or were
values used for healthy pediatric groups? How did malnutrition influence energy and protein
requirements?
Were data captured for legumes, resistant starches, dairy, fermented dairy, food additives? Please
discuss whether these factors were considered in the predictive model.
Did the authors attempt to identify food/nutrient factors that may have protective benefits to
relapse (green leafy, oily fish, fruit, B-carotene etc)?
Please comment on protein/energy malnutrition prevalence (SGA, pgSGA, GLIM etc)
“MEN was prescribed to provide 20-25% of daily energy requirements.” Did all patients receive
MEN at baseline to provide 20-25% of energy requirements? Or did some patients receive only
whole food diet?
What MEN formula was used?
While biomarker inflammation is undoubtedly important, patient symptoms are of importance
as well. Were data about symptoms captured after reintroduction?
“None had commenced or were receiving another induction therapy.” Were any patients
receiving maintenance medical therapies?
The methods for fecal starch and gluten immunogenic peptide require description, beyond  a
reference. Please describe the rationale for these readouts. Why were these readouts chosen as
opposed to gut microbiome and/or metabolomic readouts? Did the authors capture fecal bile
acids ?
In the abstract, please provide the units over time period. Was the time unit per day for all
variables?
In conclusions, authors need to be cautious about drawing conclusions about fiber as if it is a
single entity. Authors should attempt to sub-categorize fiber into soluble, insoluble, and resistant
starches..
Figure 2 – Do the green bars indicate protective factors against relapse? The authors should
discuss this in the manuscript
How was processed meat defined? Did the authors distinguish between fresh meat that was
preserved with celery salt for example compared  to smoked meat?
assistant