Gut–Liver Axis as a Therapeutic Target for Drug-Induced Liver Injury

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript reviewed that gut-liver axis as a therapeutic target for drug-induced liver injury.

This manuscript is very interesting, however, there are several concerns.

 

2.1 Gut microbiota

Please summarize the differences in the distribution of the gut microbiota in between DILI and normal and make a table or figure to visually show the decrease in beneficial gut microbiota.

 

Table 1and 2:

If possible, please add the relationship between herbs and phytochemicals, probiotics and so on, and the prevention of the progression of fatty liver, hepatitis, liver fibrosis and liver cirrhosis.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

In this review by Wenjing Tao and colleagues the authors summarize a series of studies from preclinical and clinical studies about drug-induced liver injury (DILI) and the implications of the gut-liver axis on its pathogenesis. They describe how alteration of gut microbiota as well as bacterial products and metabolites could influence the severity of DILI. They then describe the importance of the correct function of intestinal barrier and finally describe a series of therapeutic approaches (herbs and phytochemicals, probiotics, fecal microbiota transfer, postbiotics, bile acids and Farnesoid X receptor agonists) aiming at the gut-liver axis to manage/treat DILI.

The review is well written and presents several data demonstrating that liver is not an isolated organ but in contact (direct or indirect) with all other organs, thus reinforcing the concept that new therapeutic approaches need to broaden their point of view to better deal with clinical problems.

In the introduction the authors introduce DILI as a result of a series of chronic treatments with particular drugs used to treat chronic diseases or “wrong behaviour”. Since DILI could have different origin, they should better describe whether they describe acute or chronic DILI and eventually describe, if reported, what is the implication/role of such diseases compelling patients to chronic treatments (e.g diabetes or Alzheimer) in the development of DILI. Additionally, they should better clarify whether the described approaches are intended for treatment of acute or chronic DILI.

In the paragraph 2.1 in the end they stated “Taken together, some drugs could change the gut microbiota composition of patients or animals, in turn, the gut microbiota could affect the hepatotoxicity of these drugs and the severity of DILI”. Do the author know whether there are studies indicating the possibility to use some dietary supplements or additional drugs to reduce the risk of DILI development?

Likewise, at the end of paragraph 2.2 “These findings suggest that DILI is associated with damaged physical, chemical and immunological intestinal barrier”, do they know whether there are data related to prevention, reduction and cure of DILI by re-establishing the integrity of the barrier?

 

Minor comments:

Page 11 line 409-410: “FMT could alleviated the APAP-induced liver injury by reconstructing the intestinal flora structure”. Since the intestinal flora is a collection of microorganisms and not a physical structure, I would change the phrase with “…liver injury by restoring the balance/composition of the intestinal flora” or something similar.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The review "Gut-Liver Axis as a Therapeutic Target for Drug-Induced Liver Injury" discusses the deleterious effects of drugs on the gut-liver axis and also sheds light on possible mechanisms to ameliorate the effects.

It is a well discussed, thoroughly researched review paper.

I particularly fumbled a lot, while reading through line 113-119. May be a table to mention the gut microbiota and citing available literature in the context of liver damage would be helpful to the readers.

The English in the lines 138-140 was a bit hard to understand.

The therapeutic approaches for DILI in section 3 are well discussed. I would recommend the authors to also consider the possibility of a drug-natural product interaction in the case of therapeutic interventions (specifically section 3.1) and discuss that a bit.

Comments on the Quality of English Language

A few very long-winded sentences that can be broken down into simpler sentences. Otherwise, it is all good.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Authors responded for my comments.