Probiotics as Potential Therapy in the Management of Non-Alcoholic Fatty Liver Disease (NAFLD)
, Cristina Bouzas 1,2,3, Catalina M. Mascaró 1,2,3, Silvia Tejada 2,3,4 and Antoni Sureda 1,2,3Round 1
Reviewer 1 Report
The authors reviewed the potential therapeutic effects of probiotics on NAFLD and found that probiotics ameliorate NAFLD by reducing liver steatosis, normalizing the blood lipid profile and liver enzymes, exerting antioxidant effects, and regulating lipid metabolism as well as gut microbiota. This review is of great significance for guiding the application of probiotics in alleviating NAFLD. Several minor comments are listed as fellows.
1. Please describe the changes of gut microbiota in detail caused by NAFLD in section 3, and indicate references.
2. The bacterial name at the phylum level such as Firmicutes does not need italics
3. The manuscript needs to be thoroughly checked for linguistic errors. The paper is difficult to read and there are several grammatical and linguistic errors. For example, Line 58: “Liver receives via portal blood flow several metabolic products from the microbiome present in the gut.”
Author Response
[Fermentation] Manuscript ID: fermentation-2282602
Referee 1:
The authors reviewed the potential therapeutic effects of probiotics on NAFLD and found that probiotics ameliorate NAFLD by reducing liver steatosis, normalizing the blood lipid profile and liver enzymes, exerting antioxidant effects, and regulating lipid metabolism as well as gut microbiota. This review is of great significance for guiding the application of probiotics in alleviating NAFLD. Several minor comments are listed as fellows.
1.Please describe the changes of gut microbiota in detail caused by NAFLD in section 3, and indicate references.
Following the referee instructions, changes of gut microbiota have been described in section 3, the original information are described in the following references (that are included in the references section of the new version of the manuscript):
- Ursell, L. K.; Clemente, J.C.; Rideout, J. R.; Gevers, D.; Caporaso, J.G.; Knight, R. The interpersonal and intrapersonal diversity of human-associated microbiota in key body sites. J. Allergy Clin. Immunol. 2012, 129, 1204–1208
- Leung, C.; Rivera, L.; Furness, J. B.; Angus, P. W. The role of the gut microbiota in NAFLD. Nature reviews Gastroenterology & hepatology. 2016, 13(7), 412-425.
- Aron-Wisnewsky, J.; Vigliotti, C.; Witjes, J.; Le, P.; Holleboom, A. G.; Verheij, J.; Nieuwdorp, M.; Clément, K. Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders. Nature reviews. Gastroenterology & hepatology. 2020, 17(5), 279–297.
- Boursier, J.; Mueller, O.; Barret, M.; Machado, M.; Fizanne, L.; Araujo-Perez, F.; Guy, C. D.; Seed, P. C.; Rawls, J. F.; David, L. A.; et al. The severity of nonalcoholicfatty liver disease is associated with gut dysbiosis and shift in themetabolic function of the gut microbiota. Hepatology. 2016, 63, 764–775.
- Zhu, L.; Baker, S.S.; Gill, C.; Liu, W.; Alkhouri, R.; Baker, R.D.; Gill, S.R. Characterization of gut microbiomes in nonalcoholic steatohepatitis(NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2013, 57, 601–609.
- The bacterial name at the phylum level such as Firmicutes does not need italics
We agree the reviewer, all the bacterial name at the phylum level has been corrected in the new version of the manuscript.
- 3. The manuscript needs to be thoroughly checked for linguistic errors. The paper is difficult to read and there are several grammatical and linguistic errors. For example, Line 58: “Liver receives via portal blood flow several metabolic products from the microbiome present in the gut.”
According to the referee, grammatical and linguistic errors have been corrected. As well as, the indicated sentence, so the new one has been rewritten as “From the microbiome present in the gut, metabolic products are transported to the liver through the portal venous system”.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
This is an excellent review , summarizing the existing information on the potential therapeutic effect of probiotics on NAFLD. There is nothing to modify
Author Response
[Fermentation] Manuscript ID: fermentation-2282602
Referee 2:
This is an excellent review , summarizing the existing information on the potential therapeutic effect of probiotics on NAFLD. There is nothing to modify
We are glad for the revision of referee, for us it is a pleasure that our hard work has been recognized. For this reason, we want to express our gratitude to the referee for his/her time to correct our manuscript.
Author Response File: Author Response.pdf
Reviewer 3 Report
The manuscript approaches an interesting potential therapeutic application of probiotics, namely NAFLD. Revision is though required, especially regarding the table part and the presentation of animal data.
1. Line 62: "constitute a usual community present in the body". Please rephrase this construction
2. Lines 66-68: "In this sense, the regulation of the gut microbiota could have some benefits for those patients that develop NAFLD, since positive results after the intake of probiotics have been described." Please provide appropriate references.
3. Line 90, reference no. 27: Please replace this reference with the original references of the studies performed in the USA, Spain and China.
4. Please shorten the detailed definition and characteristic paragraph of probiotics.
5. Table 1 has not been cited among the text. Furthermore, it includes no data regarding the types of studies in which these were assessed. I suggest leaving this table aside and creating a table similar to table 2 (one for population-based studies and another one for animal studies) in which you add two more columns, one naming the probiotic strains which were studied and the amount administered. I suggest the same column addition in table 2, as well as an extra colum mentioning the type of study conducted.
6. Conclusions should mention as well the type of probiotics which proved to make a difference in NAFLD management.
7. English language requires revision and multiple corrections.
8. Chapter 4 should mention type of animal populations enrolled, as well as type and dosage of probiotics which were administered, in accordance with the suggested replacement of table 1.
Author Response
Please see the attachment
Author Response File: Author Response.pdf
Reviewer 4 Report
General comments
The manuscript reported an overview on the available information on the potential therapeutic effects of probiotics in NAFLD, addressing an interesting and challenging topic. In general (albeit synthetically) the manuscript is well-written, but in my opinion need some minor revisions to be suitable for publication.
Few suggestions/critical advices are reported below:
I suggest checking microorganisms’ nomenclature throughout the manuscript and reference list
1. Genera and species names often appear not in the correct form (they must be written in italic, check carefully the following lines: (145, Table 1, 158, 168, 169, 307-308, reference list)2. Check the nomenclature of Lactobacillus species throughout the manuscript They have recently renamed. I suggest using the new updated nomenclature with the related abbreviations (i.e. Lacticaseibacillus paracasei and the abbreviation should be Lcb.). Updated information on the taxonomy and nomenclature can be checked on database querying tools at the following website: http://lactotax.embl.de/wuyts/lactotax/.
3. Abstract (line 18): I suggest to replace the term “candidate” with “strategy”
4. Line 145: The Lactobacillus genus
5. Line 150: please rephrase the sentence “microbiota is the community of microrganisms that stable colonize….
Author Response
Please see the attachment
Author Response File: Author Response.pdf
Round 2
Reviewer 3 Report
the authors followed my advice and significantly improved the quality of their manuscript. There are some minor issues which still need to be solved:
1. Table 2, dosage column: please add the amount of bacteria administered, as you did in table 1.
2. There are minor English language errors present within the revised sentences.
