The Effects of Iron Supplementation and Fortification on the Gut Microbiota: A Review
, Jordie AJ Fischer 2,3, David M Goldfarb 1,3,4 and Crystal D Karakochuk 2,3,*Round 1
Reviewer 1 Report
The manuscript reviews current knowledge about possible effects of iron supplementation and fortification on human gut microbiome. Authors reviewed available animal and human trials, the results are somewhat conflicting.
Overall, the manuscript is well written, the text is clear the language is almost flawless. Conclusions are drawn correctly.
Specific comments:
Line 17: Within the gut, commensal bacteria play an essential role in maintaining systemic iron homeostasis. This suggestion is not appropriate, the microbiome may contribute to the iron homeostatis, but the host organism itself it responsible for the key regulation of the process (absorption in duodenum etc.).
Please align in the whole text.: either gut microbiome or gut microbiota
Author Response
The manuscript reviews current knowledge about possible effects of iron supplementation and fortification on human gut microbiome. Authors reviewed available animal and human trials, the results are somewhat conflicting.
Overall, the manuscript is well written, the text is clear the language is almost flawless. Conclusions are drawn correctly.
Specific comments:
Line 17: Within the gut, commensal bacteria play an essential role in maintaining systemic iron homeostasis. This suggestion is not appropriate, the microbiome may contribute to the iron homeostasis, but the host organism itself is responsible for the key regulation of the process (absorption in duodenum etc.).
Reply: The sentence on line 17 has been changed to reflect the reviewer’s comment.
Please align in the whole text.: either gut microbiome or gut microbiota
Reply: This manuscript is primarily focused on changes to the composition of gut bacteria, not to the gut bacterial genes, therefore we have changed “gut microbiome” to “gut microbiota” to ensure consistent language.
Reviewer 2 Report
The manuscript entitled with "The effects of iron supplementation and fortification on the gut microbiome: A review" summarizes the current studies between iron supplementation and gut microbiome. The manuscript is well written and organized. In the manuscript, the authors provided their searching criterion in the pubmed. However, I think the key words may not be able to cover studies in this area. Here are several major concerns listed below:
- In line 43-45, the authors provide three key words searching studies in PubMed, “human iron metabolism,” “bacterial iron metabolism,” and “the effects of iron on the gut microbiome in animals and/or humans.” I think gut microbiome may limit the studies searched on PubMed. Key words such as gut microbiota or gut flora should be included. By going through the whole manuscripts, several important studies published on FASEB J, and Science.
- Pathogenic effect of iron majorly reflected from the iron overloading, such as cancer, and hemochromatosis. The biological function of gut microbiota in regulating iron supplementation and host response should be included.
- Whether gut microbiota could be used as a biomarker to predict host iron status should be considered for host status and potential access biomarker for nutrition intervention.
- Regarding the implementation of bacteria as a therapeutic approach for several iron-related diseases, such as iron deficiency or overloading. Region or dietary effect to affect composition and function of gut microbiome, the author should discussion the potential regional effect on different population and bacterial supplementation as a therapeutic approach.
- Between Line 47 and 94, authors described the systemic iron homeostasis and known regulatory mechanism. However, the links between host iron metabolism and gut microbiome are not clearly discussed and any potential regulatory mechanisms.
Author Response
The manuscript entitled with "The effects of iron supplementation and fortification on the gut microbiome: A review" summarizes the current studies between iron supplementation and gut microbiome. The manuscript is well written and organized. In the manuscript, the authors provided their searching criterion in the pubmed. However, I think the key words may not be able to cover studies in this area. Here are several major concerns listed below:
- In line 43-45, the authors provide three key words searching studies in PubMed, “human iron metabolism,” “bacterial iron metabolism,” and “the effects of iron on the gut microbiome in animals and/or humans.” I think gut microbiome may limit the studies searched on PubMed. Key words such as gut microbiota or gut flora should be included. By going through the whole manuscripts, several important studies published on FASEB J, and Science.
Reply: Additional keywords have been added in our PubMed and MEDLINE search strategy, including gut microbiota and gut flora, as studies found in our reference list, published in FASEB J and SCIENCE do contain these key words. Lines 43-45 now state: In this literature review, we used PubMed and MEDLINE databases to search for articles related to “human iron metabolism,” “bacterial iron metabolism,” “iron and gut flora” and “the effects of iron on the gut microbiota/microbiome in animals and/or humans.”
- Pathogenic effect of iron majorly reflected from the iron overloading, such as cancer, and hemochromatosis. The biological function of gut microbiota in regulating iron
Reply: We have added a discussion on the pathogenic effects of iron overload, including hemochromatosis, thalassemias and colorectal cancer found on lines 81-99, 161-165, and 171-177.
- Whether gut microbiota could be used as a biomarker to predict host iron status should be considered for host status and potential access biomarker for nutrition intervention.
Reply: We have added a discussion from lines 226-235 on the use of gut microbiota as a biomarker.
- Regarding the implementation of bacteria as a therapeutic approach for several iron-related diseases, such as iron deficiency or overloading. Region or dietary effect to affect composition and function of gut microbiome, the author should discuss the potential regional effect on different population and bacterial supplementation as a therapeutic approach.
Reply: We agree that the geographical region of a population may affect the response to iron supplementation and the effects of the gut microbiome. We have included the following text on lines 279-281: Future studies need to analyze how varying concentrations of iron influence fecal bacteria diversity and abundance. In addition, as ethnicity and geography influence gut microbial composition, future studies also need to investigate more disparate human populations. These investigations will contribute to the developing field of microbiome-based personalized medicine.
- Between Line 47 and 94, authors described the systemic iron homeostasis and known regulatory mechanism. However, the links between host iron metabolism and gut microbiome are not clearly discussed and any potential regulatory mechanisms.
Reply: In section 3 we describe systematic iron homeostasis and known regulatory mechanisms and in section 4 (lines 106-117) we focus on the links between host iron metabolism and the gut microbiome and potential regulatory mechanisms. We discuss two mechanisms, including the synthesis and secretion of siderophores, which are high-affinity ferric iron chelators and bacteria acquiring iron directly from host proteins, using specific receptors that enable such as heme, transferrin, and lactoferrin.
We have included additional text to this section, further elaborating on this relationship and potential mechanisms of iron regulation.
Round 2
Reviewer 2 Report
I do not have any comments
