Peer Review History

Original SubmissionJune 18, 2019
Decision Letter - Florian Reichmann, Editor

PONE-D-19-17293

Dietary inulin alters the gut microbiome, enhances systemic metabolism and reduces neuroinflammation in an APOE4 relevant mouse model of preclinical Alzheimer’s Disease

PLOS ONE

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Additional Editor Comments (if provided):

Reviewer #1: This is a very interesting paper showing how preserving metabolic function through microbiota modulation AD risk can be reduced.

In my opinion the author should mention recent papers demonstrating that upon probiotics administration AD progression is counteracted based on microbiota modulation, reduction of inflammatory cytokinesm increased SCFAs, increased neuroprotective gut hormones (Bonfili L. et al. Scientific Reports 2017)

Reviewer #2: 1 The expression of APOE4 should be included after the adminstration of inulin. And more AD biomaker as Tau, BACE, p-Tau, or histopathology of brain and colon.

2 I think there are at lest two does of inulin treated groups should be proved.

3 What the dose judgment, 8% of inulin? AS: Vishal Singh et al., (2018), Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer, Cell, DOI: https://doi.org/10.1016/j.cell.2018.09.004.

4 More the correction analysis bteween the AD biomaker and gut microbiota, Metabolite.

5 Are the metabolite of Scyllo-inositol and myo-inositol is related to AD?

Reviewer #3: In their manuscript, the Authors have investigated the neuroprotective role of inulin ingestion by in vivo tests on E4FAD mice. The Authors have demonstrated that inulin has beneficial effects on microbiota and neuroinflammation. In fact, the experiments were performed to demonstrate that inulin compound have an anti-neurodegenerative role in mice fed with inulin diet. The topic is really interesting and the experiments are well designed. For this reason, I suggest only some corrections.

1. The references Nuzzo D, et al. Nutrients 2018 and Amato A et al. Nutrients 2017 should be added in the introduction to describe the link between oxidative stress and diseases.

2. I suggest to give more information regarding the mouse treatment. The Authors may add some additional information like food consumption (g for a day) and total caloric intake. How many grams of inulin are daily supplied to mice?

3. In Figure 1(D) the image of E3-control is missing.

4. The title of the article is inappropriate because the data reported are insufficient to claim a potential role of inulin for the Alzheimer disease. I suggest to remove "[…] relevant mouse model of preclinical Alzheimer's Disease" from the title.

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Revision 1

We have included the point-by-point response to the reviewer's comments in a separate file. We also addressed to the editor's request by adding the method of euthanasia and the source of the animals in our Methods section.

Attachments
Attachment
Submitted filename: Inulin Rebuttal Letter_08.06.19_final_rev.docx
Decision Letter - Florian Reichmann, Editor

Dietary inulin alters the gut microbiome, enhances systemic metabolism and reduces neuroinflammation in an APOE4 mouse model

PONE-D-19-17293R1

Dear Dr. Ai-Ling Lin,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Florian Reichmann, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Florian Reichmann, Editor

PONE-D-19-17293R1

Dietary inulin alters the gut microbiome, enhances systemic metabolism and reduces neuroinflammation in an APOE4 mouse model

Dear Dr. Lin:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Florian Reichmann

Academic Editor

PLOS ONE

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