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Review
Peer-Review Record

The Metabolites Produced by Lactic Acid Bacteria and Their Role in the Microbiota–Gut–Brain Axis

Fermentation 2025, 11(7), 378; https://doi.org/10.3390/fermentation11070378
by Yulma Lizbeth Aguirre-Garcia 1, Neftiti Carolina Cerda-Alvarez 1, Rosa María Santiago-Santiago 1, Adriana Rocío Chantre-López 1, Sarahi Del Carmen Rangel-Ortega 2 and Raúl Rodríguez-Herrera 1,*
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 3: Anonymous
Fermentation 2025, 11(7), 378; https://doi.org/10.3390/fermentation11070378
Submission received: 1 May 2025 / Revised: 8 June 2025 / Accepted: 14 June 2025 / Published: 30 June 2025

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This paper presents an overview of the available research regarding the interplay between the host organism and the gut microbiota, particularly within the brain-gut axis. In my opinion, the issue is a fairly well-studied and described topic. Extensive studies on this topic have already appeared in the last years, 2023-2025. However, it can be considered that the prepared manuscript allows a quick and simple familiarisation with the topic; the tables and figures present key information taken from research papers, which facilitates the assimilation of basic information.

On the other hand, I believe that the collection of cited research papers lacked several publications, including those addressing the topic of EPSs produced by microorganisms that make up the gut microbiota and the importance of these substances in the proper functioning of the brain-gut axis. Suggested publications include:

https://doi.org/10.1038/s41598-020-65147-1

https://doi.org/10.1016/j.procbio.2021.04.003

https://doi.org/10.3389/fmicb.2023.1209067

In addition, it is worth highlighting the role of bacteria belonging to probiotic strains of the genus Bifidobacterium, if only to provide additional information on their role in ASDs (autism spectrum disorders). Suggested publications include:

Please correct the errors listed below:

Line 286 – I assume that there should be LAB, not BAL

Table 4 – „Albino rats” not „Rats albinas”

Author Response

Consulte el archivo adjunto.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

This article presents a comprehensive overview of the role of lactic acid bacteria (LAB) and their metabolites in modulating the microbiota-gut-brain axis (MGBA). The authors effectively summarize current research on LAB's ability to produce bioactive compounds, such as lactic acid, short-chain fatty acids (SCFAs), and gamma-aminobutyric acid (GABA), which have been shown to impact brain function and overall health. The paper is well-organized, citing numerous studies to support its claims and providing valuable insights into potential therapeutic applications.

  1. The review is comprehensive; however, the novelty is a little lacking, the review primarily summarizes existing research rather than presenting new findings or hypotheses. This limits its potential impact in driving forward the field.
  2. The review needs to depth in some areas, such as the specific mechanisms by which LAB metabolites influence the MGBA, are discussed at a high level. More in-depth analyses could provide further insights.

‌3. ‌Expand on Mechanisms‌: Providing a more in-depth discussion of the underlying mechanisms by which LAB metabolites affect the MGBA would strengthen the paper's scientific merit.

Comments on the Quality of English Language

This article presents a comprehensive overview of the role of lactic acid bacteria (LAB) and their metabolites in modulating the microbiota-gut-brain axis (MGBA). The authors effectively summarize current research on LAB's ability to produce bioactive compounds, such as lactic acid, short-chain fatty acids (SCFAs), and gamma-aminobutyric acid (GABA), which have been shown to impact brain function and overall health. The paper is well-organized, citing numerous studies to support its claims and providing valuable insights into potential therapeutic applications.

  1. The review is comprehensive; however, the novelty is a little lacking, the review primarily summarizes existing research rather than presenting new findings or hypotheses. This limits its potential impact in driving forward the field.
  2. The review needs to depth in some areas, such as the specific mechanisms by which LAB metabolites influence the MGBA, are discussed at a high level. More in-depth analyses could provide further insights.

‌3. ‌Expand on Mechanisms‌: Providing a more in-depth discussion of the underlying mechanisms by which LAB metabolites affect the MGBA would strengthen the paper's scientific merit.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

Manuscript ID: fermentation-3648729

Title: Metabolites Produced by Lactic Acid Bacteria and Their Role in the Microbiota-Gut-Brain Axis

Authors: Aguirre-Garcia Yulma Lizbeth, Cerda-Alvares Neftiti Carolina, Santiago-Santiago Rosa María, Chantre-López Adriana Rocío, Rangel-Ortega Sarahi Del Carmen, Rodríguez-Herrera Raúl

 

This review summarizes some lactic acid bacteria with probiotic potential, their metabolites resulting from the fermentation process, together with their impact on the gut-brain axis modulation, highlighting some mechanisms by which these compounds can influence human health.

In my opinion, the manuscript lacks a clear and logical organization. Also, the information provided is overly simplistic, and some points are too general (such as: subchapters 2.2. Fermentation Mechanisms and Metabolite Production, 2.3. Factors Influencing Metabolite Production).

The criteria used to select references are not clearly defined—was a systematic review approach applied?

Other suggestions:

Line 70-72. Correct the sentence considering that not all the LAB species are classified as GRAS.

Line 73-74. Please reconsider the sentence because not all the LAB are probiotics. I suggest including in the text all the properties required for a strain to be considered probiotic.

For Table 1: What criteria were used to select only these specific types of substrates/matrixes? The avocado seed is not a fermentation effect. What is BAL?

Table 2 should be improved with other more effects of short chain fatty acids on the gut-brain axis.

It appears that Table 3 is missing from the manuscript. Please, see line 250.

Please revise all the names of lactic acid bacteria to reflect the updated taxonomic classification.

All the abbreviation should be explained upon first use (hormones CCK, GIP, PYY, etc.)

Some information is repeated. Please see lines 250-270 from Chapter 4.  

 

Comments on the Quality of English Language

I recommend comprehensive English editing to enhance clarity.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors responsed all the comments, now it can be accepted.

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript has been improved and I agree to its publication in its current form.

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