Reviewer's report
Title:Association of Gut Microbiota with Post-operative Clinical Course in
Crohn's Disease
Version: 2Date:13 April 2013
Reviewer: Ashwin Ananthakrishnan
Reviewer's report:
There is considerable interest in the role of intestinal microbiota in Crohn’s
disease. Several prior studies have clarified the reduction in biodiversity in
Crohn’s disease patients using culture-independent techniques, and have
suggested variable depletion of particular phylogenetic groups. In addition,
ongoing inflammation, medication use, environment and diet have all been
correlated with variations in the gut flora. In this interesting study, Dey et al.
perform next-generation microbial sequencing of the gut microbiome on a cohort
of 6 CD patients undergoing ileocolonic resection, comparing the microbial profile
at the time of surgery to that obtained at the 6 month surveillance colonoscopy.
The group is further compared to patients undergoing colonoscopy for
surveillance, non-IBD patients undergoing surgery or a surveillance colonoscopy.
The authors identify a reduced overall biodiversity from the surgical samples (at
IC resection) of patients who subsequently developed endoscopically significant
recurrence (i2 lesions) when compared to controls undergoing IC resection. On
the other hand, patients who remained without recurrence or had only minor
endoscopic recurrence on their follow-up were more similar to controls.
Overall, the study is quite interesting and in an important area of research. The
authors followed a standard protocol for sample collection, and used high-quality
scientific tools for microbial sequencing and analysis. I think their findings are
important and make a contribution to the literature in this area. However, there
are a few points that merit some classification or acknowledgement.
1. One major limitation of the manuscript is that only a very small number of
patients could be enrolled. Given the acknowledged heterogeneity in Crohn’s
disease, there is substantial inter-individual variation. Indeed as identified by the
authors – the variation in biodiversity and phylla between CD patients is greater
than that seen when compared to controls. Thus, having a larger sample size
would allow for greater confidence in their results and improve the
generalizability of their findings. Particularly important as at the end – we are
comparing 3 patients without recurrence and 3 with recurrence.
2. The authors report on use of anti-TNF biologics or natalizumab in their cohort
of CD. However was this use pre-operative or post-operative? Were any patients
continued on medications post-operatively to prevent recurrence? This may be
an important factor influencing both likelihood of recurrence and potentially the
microbial composition?
3. Were any of the patients smokers? And did that influence microbial
composition, likelihood of recurrence, or thestrength of the association identified?
4. Were any of the patients on antibiotics post-operatively for prevention of
recurrence?
5. Please also provide greater details regarding the initial surgery as much of the
analysis is guided by sequencing the surgical biopsies from the resection. Did all
patients undergo surgery for failure of medical management? Did any undergo
resection purely for fibrostenosing disease? Did histologic examination of the
surgical specimens confirm significant ongoing inflammation in all? Did any
patients have penetrating disease at the time of surgery? Please account for the
above variables in your analysis and adjust for them in a multivariate model to
examine if the pair-wise comparisons still hold.
6. Much of the supplemental methods replicate what is already presented in the
same detail in the manuscript – particularly with regards to the sequencing
methods. Please consider providing an informative but abbreviated version within
the body of the manuscript and providing the rest in the supplemental file.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no competing interests.
Reviewer's report
Title:Association of Gut Microbiota with Post-operative Clinical Course in
Crohn's Disease
Version: 2Date:13 April 2013
Reviewer: Ashwin Ananthakrishnan
Reviewer's report:
There is considerable interest in the role of intestinal microbiota in Crohn’s
disease. Several prior studies have clarified the reduction in biodiversity in
Crohn’s disease patients using culture-independent techniques, and have
suggested variable depletion of particular phylogenetic groups. In addition,
ongoing inflammation, medication use, environment and diet have all been
correlated with variations in the gut flora. In this interesting study, Dey et al.
perform next-generation microbial sequencing of the gut microbiome on a cohort
of 6 CD patients undergoing ileocolonic resection, comparing the microbial profile
at the time of surgery to that obtained at the 6 month surveillance colonoscopy.
The group is further compared to patients undergoing colonoscopy for
surveillance, non-IBD patients undergoing surgery or a surveillance colonoscopy.
The authors identify a reduced overall biodiversity from the surgical samples (at
IC resection) of patients who subsequently developed endoscopically significant
recurrence (i2 lesions) when compared to controls undergoing IC resection. On
the other hand, patients who remained without recurrence or had only minor
endoscopic recurrence on their follow-up were more similar to controls.
Overall, the study is quite interesting and in an important area of research. The
authors followed a standard protocol for sample collection, and used high-quality
scientific tools for microbial sequencing and analysis. I think their findings are
important and make a contribution to the literature in this area. However, there
are a few points that merit some classification or acknowledgement.
1. One major limitation of the manuscript is that only a very small number of
patients could be enrolled. Given the acknowledged heterogeneity in Crohn’s
disease, there is substantial inter-individual variation. Indeed as identified by the
authors – the variation in biodiversity and phylla between CD patients is greater
than that seen when compared to controls. Thus, having a larger sample size
would allow for greater confidence in their results and improve the
generalizability of their findings. Particularly important as at the end – we are
comparing 3 patients without recurrence and 3 with recurrence.
2. The authors report on use of anti-TNF biologics or natalizumab in their cohort
of CD. However was this use pre-operative or post-operative? Were any patients
continued on medications post-operatively to prevent recurrence? This may be
an important factor influencing both likelihood of recurrence and potentially the
microbial composition?
3. Were any of the patients smokers? And did that influence microbial
composition, likelihood of recurrence, or thestrength of the association identified?
4. Were any of the patients on antibiotics post-operatively for prevention of
recurrence?
5. Please also provide greater details regarding the initial surgery as much of the
analysis is guided by sequencing the surgical biopsies from the resection. Did all
patients undergo surgery for failure of medical management? Did any undergo
resection purely for fibrostenosing disease? Did histologic examination of the
surgical specimens confirm significant ongoing inflammation in all? Did any
patients have penetrating disease at the time of surgery? Please account for the
above variables in your analysis and adjust for them in a multivariate model to
examine if the pair-wise comparisons still hold.
6. Much of the supplemental methods replicate what is already presented in the
same detail in the manuscript – particularly with regards to the sequencing
methods. Please consider providing an informative but abbreviated version within
the body of the manuscript and providing the rest in the supplemental file.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Association of Gut Microbiota with Post-operative Clinical Course in
Crohn's Disease
Version: 2Date:13 April 2013
Reviewer: Ashwin Ananthakrishnan
Reviewer's report:
There is considerable interest in the role of intestinal microbiota in Crohn’s
disease. Several prior studies have clarified the reduction in biodiversity in
Crohn’s disease patients using culture-independent techniques, and have
suggested variable depletion of particular phylogenetic groups. In addition,
ongoing inflammation, medication use, environment and diet have all been
correlated with variations in the gut flora. In this interesting study, Dey et al.
perform next-generation microbial sequencing of the gut microbiome on a cohort
of 6 CD patients undergoing ileocolonic resection, comparing the microbial profile
at the time of surgery to that obtained at the 6 month surveillance colonoscopy.
The group is further compared to patients undergoing colonoscopy for
surveillance, non-IBD patients undergoing surgery or a surveillance colonoscopy.
The authors identify a reduced overall biodiversity from the surgical samples (at
IC resection) of patients who subsequently developed endoscopically significant
recurrence (i2 lesions) when compared to controls undergoing IC resection. On
the other hand, patients who remained without recurrence or had only minor
endoscopic recurrence on their follow-up were more similar to controls.
Overall, the study is quite interesting and in an important area of research. The
authors followed a standard protocol for sample collection, and used high-quality
scientific tools for microbial sequencing and analysis. I think their findings are
important and make a contribution to the literature in this area. However, there
are a few points that merit some classification or acknowledgement.
1. One major limitation of the manuscript is that only a very small number of
patients could be enrolled. Given the acknowledged heterogeneity in Crohn’s
disease, there is substantial inter-individual variation. Indeed as identified by the
authors – the variation in biodiversity and phylla between CD patients is greater
than that seen when compared to controls. Thus, having a larger sample size
would allow for greater confidence in their results and improve the
generalizability of their findings. Particularly important as at the end – we are
comparing 3 patients without recurrence and 3 with recurrence.
2. The authors report on use of anti-TNF biologics or natalizumab in their cohort
of CD. However was this use pre-operative or post-operative? Were any patients
continued on medications post-operatively to prevent recurrence? This may be
an important factor influencing both likelihood of recurrence and potentially the
microbial composition?
3. Were any of the patients smokers? And did that influence microbial
composition, likelihood of recurrence, or thestrength of the association identified?
4. Were any of the patients on antibiotics post-operatively for prevention of
recurrence?
5. Please also provide greater details regarding the initial surgery as much of the
analysis is guided by sequencing the surgical biopsies from the resection. Did all
patients undergo surgery for failure of medical management? Did any undergo
resection purely for fibrostenosing disease? Did histologic examination of the
surgical specimens confirm significant ongoing inflammation in all? Did any
patients have penetrating disease at the time of surgery? Please account for the
above variables in your analysis and adjust for them in a multivariate model to
examine if the pair-wise comparisons still hold.
6. Much of the supplemental methods replicate what is already presented in the
same detail in the manuscript – particularly with regards to the sequencing
methods. Please consider providing an informative but abbreviated version within
the body of the manuscript and providing the rest in the supplemental file.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no competing interests.
assistant