Gut Health Optimization in Canines and Felines: Exploring the Role of Probiotics and Nutraceuticals
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
This review has a very good structure and writing, but a few small problems need to be further modified, specific comments are as follows:
1.Line 66: Remove excessive punctuation "."
2.How do you define “nutraceuticals”? and what are the differences between nutraceuticals and antioxidants?
3.Line 113: “Clostridium” should be italicized
4.“Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria,” Please confirm whether need to italic?
5. What gut microbiota reflects the different dietary styles of dogs and cats?
6. Line 142: “Notably, Acute diarrhea and other short-term.....” “Acute” First letters should be lowercase.
7. Line 148-149: “Most pets visit veterinarians because of digestive problems that can lead to an imbalance in the gut microbiota.” This sentence is the summary of the paragraph, but the following related sentence content is not related to the summary sentence.
8. Line 176: “inflammatory bowel disease (IBD),” ,“IBD” IS ok in this place.
9. Line 198-199: “Enterococcus, Pasteurella, Dietzia, and Escherichia increased. Interestingly, some bacterial species, including Prevotellaceae, Streptomycetaceae, and Spirochaetes” All name of bacteria should be italicized.
10. What are the challenges of “Probiotics and Nutraceuticals” in the management of pet gut health? And supplement the related content in the manuscript.
Author Response
*AU= Authors’ response
Reviewer 1
This review has a very good structure and writing, but a few small problems need to be further modified, specific comments are as follows:
AU: Thank you for the positive remark.
1.Line 66: Remove excessive punctuation "."
AU: Thank you. The suggested change/changes have been made.
- How do you define “nutraceuticals”? and what are the differences between nutraceuticals and antioxidants?
AU: Thank you for your question. Plants or their derived vegetables in untreated forms have antioxidant potential and can minimize the harmful effects of redox reactions that occur in metabolic pathways, by scavenging free radicals [1]. These dietary antioxidants are diverse molecules that work by neutralizing free radicals and promoting overall gut health [2]. Moreover, a broader category of products called nutraceuticals (that includes phytochemicals as well as antioxidants) are derived from food sources and employed to provide beyond basic nutrition [3]. They are administered in an adequate dose to improve various conditions, including the maintenance of a healthy gut [4].
- Line 113: “Clostridium” should be italicized
AU: The suggested change/changes have been made.
4.“Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria,” Please confirm whether need to italic?
AU: Thank you for the note. NO. These are phyla and adequate without italics.
- What gut microbiota reflects the different dietary styles of dogs and cats?
AU: Thank you for your question. The dog and cat microbiome are dominant in different phyla. While canine guts are dominated by Fusobacteria, feline guts possess more members from Firmicutes. Also, the latter have more members from Bacteroides and Prevotella phyla. These differences are mostly attributed to diet as cats are obligate carnivores, but dogs are omnivores [5].
- Line 142: “Notably, Acute diarrhea and other short-term.....” “Acute” First letters should be lowercase.
AU: Thank you for the correction. The suggested change/changes have been made.
- Line 148-149: “Most pets visit veterinarians because of digestive problems that can lead to an imbalance in the gut microbiota.” This sentence is the summary of the paragraph, but the following related sentence content is not related to the summary sentence.
AU: Thank you for the observation. The sentence has been rephrased as” Most pets visit veterinarians because of digestive problems that can lead to an imbalance in the gut microbiota. Upon diagnosis, several bacterial infections have been found in dogs, including Campylobacter and Salmonella, that can spread to humans.”
- Line 176: “inflammatory bowel disease (IBD),” ,“IBD” IS ok in this place.
AU: Thank you. The suggested change/changes have been made.
- Line 198-199: “Enterococcus, Pasteurella, Dietzia, and Escherichia increased. Interestingly, some bacterial species, including Prevotellaceae, Streptomycetaceae, and Spirochaetes” All name of bacteria should be italicized.
AU: Thank you. The suggested change/changes have been made.
- What are the challenges of “Probiotics and Nutraceuticals” in the management of pet gut health? And supplement the related content in the manuscript.
AU: Thank you for the suggestion. The manuscript has been revised to include information on this;
“4.1 The challenges associated with Probiotics and Nutraceuticals use
While probiotic supplements show promise in promoting gut health by influencing the gut microbiome in pets, several limitations might hinder their widespread use. For, instance, delivering live bacteria to the target location (the intestines) is very challenging. The harsh acidic environment of the stomach can kill unprotected probiotics. To curb this issue, encapsulation techniques have been developed but these increase the overall cost and raise safety concerns [6]. Moreover, natural antibiotic supplements (bacteriocins) produced by gut bacteria has certain limitations. Particularly, their production is time consuming and expensive [7]. Likewise, nutraceutical manufacture may suffer from inconsistency in quality control that might raise safety concerns. Besides, the need for nutraceutical dose optimization for every organism, and lack of rules quality assessment further complicates the administration [8]”.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Comments and Suggestions for AuthorsGut Health Optimization in Canines and Felines: Exploring the Role of Probiotics and Nutraceuticals
The authors have presented a review on the use of probiotics or nutraceuticals to improve the health of dogs and cats.This is a review work, however, there are many weak points, among which the lack of references in many of the aspects and works that are cited stands out. Furthermore, some concepts are not presented in the text adequately and some paragraphs appear disorganized, commenting on aspects that have been presented previously.
The review on the use of probiotics and nutraceuticals in my opinion is very limited and many studies have not been included. Furthermore, hardly any information is presented in the tables on studies in dogs or cats with gastrointestinal problems, in which there are possibly more studies than in other pathologies. In my opinion the work needs to be reviewed extensively before new submission.
Line 35, s. The animal….
Start a new paragraph with “The animal….”
Line 54. “inflammatory potential, and regulate energy metabolism.”
Include references for each effect.
Line 59, Your have not defined what probiotics are. This should firts introduce what you are talking about
Line 79, These enzymes are a in turn
Delete “a”
Line 92 Probiotics and nutraceuticals
At the beginning of the paragraph you were talking about antioxidants. It is not clear what do you mean with nutraceuticals. You should cleary these terms before using them.
TAble 1. Activities performed by gut microbiota
Gut microbiota of dogs and cats?
Line 104 “Dogs and cats have different microbiomes, even though they have a similar gut 104 microbial community dominated by Firmicutes, Bacteroidetes, Proteobacteria, and Fusobac- 105 teria, as depicted by 16S rRNA sequencing”
Include references
Line 108 “It is inter- 108 esting to note that as these microorganisms exist at different positions in the digestive 109 system, their concentrations and varieties diversify.”
Include reference
Line 110. “. This demonstrated the distinct and 110 species-specific ecology of the digestive systems of dogs and cats.”
Include reference
Lines 104-114. , breed….
Include futher information on changes by breeds or geographic location
Lines 123, It is interesting to note that 123 intestinal lactobacilli in cats are similar to those in dogs;
Include reference
Lines 130-133. This microbial community performs numerous tasks, such as producing vital nutrients 130 through fermentation and metabolic processes, helping develop and mature the intesti- 131 nal epithelium and immune system, and competitively maintaining enteric pathogens 132 (colonization resistance)”
Include references for each task
Line 157. You have not defined what CE is
Line 158 to how the patient reacts to dietary modifications, antibiotics, or steroids.
Include reference
Line 159. “, idiopathic and IBD is”
Is this the same CE¿. It is not clear the classification for these Ces
Line 164, One important contributing factor is microbial dysbiosis, which is 164 characterized by changes in the composition of the gut microbiota.”
Include reference
Line 165-167 “Research on several 165 species has repeatedly demonstrated a correlation between IBD and an increase in gram- 166 negative bacteria such as Enterobacteriaceae and a decline in Firmicutes. “
Include reference
Line 167 “Specific abnor- 167 malities have been demonstrated by a comprehensive investigation of the gut flora in 168 dogs and cats with IBD.”
You already say this in the same paragraph
Line 169-171. “For example, compared to healthy controls, researchers discov- 169 ered that dogs with IBD had lower numbers of Prevotellaceae, Clostridiales, Bacteroidaceae, 170 and Fusobacteria.”
Include reference.
And what about the SCFAs production in IBD dogs??. There are some research that found some information about it.
Lines 180-182. “These findings indicate that the 180 gut microbiota, inflammatory immune response, or both may impact the onset of IBD in 181 companion animals”
Provide further information on the inflammatory immune response. This is a review.
Line 182-184 “It is very likely that toll-like receptors (TLRs), known for their abil- 182 ity to recognize microbial patterns and trigger inflammation, play a significant role in 183 this process.”
Include reference
Line 193-194. “For instance, tylosin is a macrolide 193 antibiotic whose effects on the gut flora of dogs were examined in a recent study”
Include reference
Line 203-206. In this paragraph you just include 1 reference with very different ideas?
Line 240. “Moreover, researchers have investigated the effects of the probiotic strain L. acidophilus 240 DSM13241 in healthy cats”
Include reference
Line 279. “however, the data are not” change by “data were not “
Lines 295-297. “These new chemicals may pos- 295 sess characteristics that support the regulation of cell growth, alter the immune system, 296 or combat microorganisms.”
Include references for each effect.
Lines 308-313. “Antibiotics can have unexpected effects even ………………….”
You already talked about antibiotics before. Maybe you can move this paragraph.
Line 314-320. “It should be noted that dogs and cats, despite their shared status as companion animals, 314 may have differing dietary needs when managing CE”
You already talked about CE. Move this paragraph to that place. You are now taking about nutraceuticals.
Line 331, “the plant Boswellia serrata (B. serrata), which is a mem- 331 ber of the Burseraceae family, is a source of frankincense, a resin with therapeutic quali- 332 ties”
Include reference
Lines 354-355. vitamins A and E”
And what about other vitamins. You provide very limited information.
Table 2. You could Include age of the dogs
You have not included any information on IBD dogs, but talked about it in the text.
Comments on the Quality of English LanguageMinor changes required
Author Response
Reviewer 2
The authors have presented a review on the use of probiotics or nutraceuticals to improve the health of dogs and cats.This is a review work, however, there are many weak points, among which the lack of references in many of the aspects and works that are cited stands out. Furthermore, some concepts are not presented in the text adequately and some paragraphs appear disorganized, commenting on aspects that have been presented previously.
The review on the use of probiotics and nutraceuticals in my opinion is very limited and many studies have not been included. Furthermore, hardly any information is presented in the tables on studies in dogs or cats with gastrointestinal problems, in which there are possibly more studies than in other pathologies. In my opinion the work needs to be reviewed extensively before new submission.
AU: Thank you very much for your constructive criticism. The manuscript has been reviewed and modified accordingly.
Line 35, s. The animal….
Start a new paragraph with “The animal….”
AU: Thank you for the observation. Text corrected.
Line 54. “inflammatory potential, and regulate energy metabolism.”
Include references for each effect.
AU: Thank you. References added.
Line 59, Your have not defined what probiotics are. This should first introduce what you are talking about
AU: Thank you for the observation. Text modified accordingly to briefly define what probiotics are; “Evidently, the gut microbiota plays an essential role in human and animal health. To maintain a balance in the gut microbiome, live microorganisms called “probiotics” that include bacteria and yeasts, are administered in adequate doses and offer a promising strategy for gut microbiome manipulation”.
Line 79, These enzymes are a in turn
Delete “a”
AU: Thank you. Done.
Line 92 Probiotics and nutraceuticals
At the beginning of the paragraph you were talking about antioxidants. It is not clear what do you mean with nutraceuticals. You should cleary these terms before using them.
AU: Thank you for the comment. Text modified and terms have been further clarified.
Table 1. Activities performed by gut microbiota
Gut microbiota of dogs and cats?
AU: Yes. The table name has been modified accordingly.
Line 104 “Dogs and cats have different microbiomes, even though they have a similar gut 104 microbial community dominated by Firmicutes, Bacteroidetes, Proteobacteria, and Fusobac- 105 teria, as depicted by 16S rRNA sequencing”
Include references
AU: Thank you for the comment. References included.
Line 108 “It is inter- 108 esting to note that as these microorganisms exist at different positions in the digestive 109 system, their concentrations and varieties diversify.”
Include reference
AU: Thank you for your comment. The section had been modified.
Line 110. “. This demonstrated the distinct and 110 species-specific ecology of the digestive systems of dogs and cats.”
Include reference
AU: Thank you. Text modified accordingly.
Lines 104-114. , breed….
Include futher information on changes by breeds or geographic location
AU: Thank you for the suggestion. Text modified accordingly.
Lines 123, It is interesting to note that 123 intestinal lactobacilli in cats are similar to those in dogs;
Include reference
AU: The suggested change/changes have been made.
Lines 130-133. This microbial community performs numerous tasks, such as producing vital nutrients 130 through fermentation and metabolic processes, helping develop and mature the intesti- 131 nal epithelium and immune system, and competitively maintaining enteric pathogens 132 (colonization resistance)”
Include references for each task
AU: Thank you for your keen observation. The suggested changes have been made.
Line 157. You have not defined what CE is
AU: Thank you for the comment. Text modified accordingly.
Line 158 to how the patient reacts to dietary modifications, antibiotics, or steroids.
Include reference
AU: The suggested change/changes have been made.
Line 159. “, idiopathic and IBD is”
Is this the same CE¿. It is not clear the classification for these Ces
AU: Thank you for your question. Yes, idiopathic inflammatory bowel disease (IBD) is a subtype of Chronic enteropathies that are characterized by inflammation in the gastrointestinal tract. "idiopathic" elaborates on its unknown origin. Text modified accordingly.
Line 164, One important contributing factor is microbial dysbiosis, which is 164 characterized by changes in the composition of the gut microbiota.”
Include reference
AU: The suggested change/changes have been made.
Line 165-167 “Research on several 165 species has repeatedly demonstrated a correlation between IBD and an increase in gram- 166 negative bacteria such as Enterobacteriaceae and a decline in Firmicutes. “
Include reference
AU: The suggested change/changes have been made.
Line 167 “Specific abnor- 167 malities have been demonstrated by a comprehensive investigation of the gut flora in 168 dogs and cats with IBD.”
You already say this in the same paragraph
AU: Thank you for your observation. The repetitive sentence has been removed.
Line 169-171. “For example, compared to healthy controls, researchers discov- 169 ered that dogs with IBD had lower numbers of Prevotellaceae, Clostridiales, Bacteroidaceae, 170 and Fusobacteria.”
Include reference.
AU: The suggested change/changes have been made.
And what about the SCFAs production in IBD dogs??. There are some research that found some information about it.
AU: Thank you for the comment. A relevant study has been added
Lines 180-182. “These findings indicate that the 180 gut microbiota, inflammatory immune response, or both may impact the onset of IBD in 181 companion animals”
Provide further information on the inflammatory immune response. This is a review.
AU: Thank you for the observation. The section was written to highlight the probiotics (i.e. microbes and not the inflammatory response). However, a few lines have been added to address the reviewer’s comment which is a very good comment.
“In a healthy gut these sensor TLRs help to maintain a balance by triggering appropriate immune response when required. However, in case of IBD, the balance is disrupted. Under normal conditions the TLR signaling is beneficial but when the regulatory cells are impaired in diseased state (IBD), the otherwise suppressed abnormally excessive immune response is triggered. Therefore T helper cells become overactive and significantly damage the gut homeostasis and microbiome, leading to inflammation [11]”.
Line 182-184 “It is very likely that toll-like receptors (TLRs), known for their abil- 182 ity to recognize microbial patterns and trigger inflammation, play a significant role in 183 this process.”
Include reference
AU: The suggested change/changes have been made.
Line 193-194. “For instance, tylosin is a macrolide 193 antibiotic whose effects on the gut flora of dogs were examined in a recent study”
Include reference
AU: The suggested change/changes have been made.
Line 203-206. In this paragraph you just include 1 reference with very different ideas?
AU: Thank you for your observation. The text has been modified to include 2 relevant references.
Line 240. “Moreover, researchers have investigated the effects of the probiotic strain L. acidophilus 240 DSM13241 in healthy cats”
Include reference
AU: The suggested change/changes have been made.
Line 279. “however, the data are not” change by “data were not “
AU: Thank you. The suggested change/changes have been made.
Lines 295-297. “These new chemicals may pos- 295 sess characteristics that support the regulation of cell growth, alter the immune system, 296 or combat microorganisms.”
Include references for each effect.
AU: Thank you. The suggested change/changes have been made.
Lines 308-313. “Antibiotics can have unexpected effects even ………………….”
You already talked about antibiotics before. Maybe you can move this paragraph.
AU: Thank you for your observation. The lines have been adjusted.
Line 314-320. “It should be noted that dogs and cats, despite their shared status as companion animals, 314 may have differing dietary needs when managing CE”
You already talked about CE. Move this paragraph to that place. You are now taking about nutraceuticals.
AU: Thank you for the good point. CE has been changed to gut diseases, because we are discussing the use of nutraceuticals to mitigate the effect of gut diseases/disorders, such as CE, hence, the need to refer to the problem in writing the solutions. Text improved accordingly.
Line 331, “the plant Boswellia serrata (B. serrata), which is a mem- 331 ber of the Burseraceae family, is a source of frankincense, a resin with therapeutic quali- 332 ties”
Include reference
AU: Thank you very much. The suggested change/changes have been made.
Lines 354-355. vitamins A and E”
And what about other vitamins. You provide very limited information.
AU: Thank you for the comment. These are the most comprehensively studied vitamins. Data about vitamin b12 and D have been added and the text is modified for more clarity.
Table 2. You could include age of the dogs
AU: Not all studies state the ages of dogs so we have kept it generalized earlier to maintain consistency. Those that are available have been added as per your suggestion.
You have not included any information on IBD dogs, but talked about it in the text.
AU: Thank you. The suggested change/changes have been made.
Comments on the Quality of English Language
Minor changes required
AU: Thank you for your invaluable suggestions and helpful review. The manuscript has been modified accordingly.
References
- Riaz Rajoka, M.S.; Thirumdas, R.; Mehwish, H.M.; Umair, M.; Khurshid, M.; Hayat, H.F.; Phimolsiripol, Y.; Pallarés, N.; Martí-Quijal, F.J.; Barba, F.J. Role of food antioxidants in modulating gut microbial communities: Novel understandings in intestinal oxidative stress damage and their impact on host health. Antioxidants 2021, 10, 1563.
- Young, D.; Tsao, R.; Mine, Y. Nutraceuticals and antioxidant function. Functional foods, nutraceuticals, and degenerative disease prevention 2011, 75-112.
- Jain, N.; Ramawat, K.G. Nutraceuticals and antioxidants in prevention of diseases. Natural products 2013, 2559-2580.
- Catinean, A.; Neag, M.A.; Muntean, D.M.; Bocsan, I.C.; Buzoianu, A.D. An overview on the interplay between nutraceuticals and gut microbiota. PeerJ 2018, 6, e4465.
- Lee, D.; Goh, T.W.; Kang, M.G.; Choi, H.J.; Yeo, S.Y.; Yang, J.; Huh, C.S.; Kim, Y.Y.; Kim, Y. Perspectives and advances in probiotics and the gut microbiome in companion animals. Journal of Animal Science and Technology 2022, 64, 197.
- Wolfe, W.; Xiang, Z.; Yu, X.; Li, P.; Chen, H.; Yao, M.; Fei, Y.; Huang, Y.; Yin, Y.; Xiao, H. The challenge of applications of probiotics in gastrointestinal diseases. Advanced Gut & Microbiome Research 2023, 2023, 1984200.
- Hernández-González, J.C.; Martínez-Tapia, A.; Lazcano-Hernández, G.; García-Pérez, B.E.; Castrejón-Jiménez, N.S. Bacteriocins from lactic acid bacteria. A powerful alternative as antimicrobials, probiotics, and immunomodulators in veterinary medicine. Animals 2021, 11, 979.
- Siddiqui, R.A.; Moghadasian, M.H. Nutraceuticals and nutrition supplements: Challenges and opportunities. Nutrients 2020, 12, 1593.
- Simpson, J.; Martineau, B.; Jones, W.; Ballam, J.; Mackie, R.I. Characterization of fecal bacterial populations in canines: effects of age, breed and dietary fiber. Microbial ecology 2002, 44, 186-197.
- Minamoto, Y.; Minamoto, T.; Isaiah, A.; Sattasathuchana, P.; Buono, A.; Rangachari, V.R.; McNeely, I.H.; Lidbury, J.; Steiner, J.M.; Suchodolski, J.S. Fecal short‐chain fatty acid concentrations and dysbiosis in dogs with chronic enteropathy. Journal of veterinary internal medicine 2019, 33, 1608-1618.
- Lu, Y.; Li, X.; Liu, S.; Zhang, Y.; Zhang, D. Toll-like receptors and inflammatory bowel disease. Frontiers in immunology 2018, 9, 72.
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsAccept in present form
Author Response
Thank you for your invaluable review.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe authors have improved the writing of the article and its organization. However, there are still some aspects that need to be reviewed. Above all, the inclusion of some references that do not appear and should appear as it is a review article.
Lines 122-123 While canine guts are dominated by Fusobacteria, feline guts possess more members from Firmicutes. Also, the latter have more members from Bacterocides and Prevotella phyla.
Include references
Lines 187-190 Another study suggested a strong link between SCFAs in the gut and GI disorders like col- orectal cancer and IBD. It was observed that reduced levels of SCFAs in dogs were asso- 189 ciated with the progression of GI disorders just like in human subjects [70]
There are other studies in dogs in which SCFAs are affected. This is a review article.
Lines 230-231 . These bacteria can be classified as defined or undefined. Probiotics support healthy gut microbiota by generating substances that combat bad bacteria, dis- placing pathogens for available space, and possibly affecting the immune system.
Include references
Lines 2390 During feeding, they have the ability to persist and even take over the lactic acid bacteria (LAB) in the small intestine, which may have an impact on gut ecology.
Include reference
Comments on the Quality of English LanguageMINOR CHANGES REQUIRED
Author Response
Please see the attachment.
Author Response File: Author Response.docx
