Title: Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic
uncomplicated diverticular disease: results from an observational cohort study
Version: 0 Date: 28 Oct 2022
Reviewer's report:
This study assessed the effect of cyclic treatment with rifaximin on the fecal microbiota of SUDD
patients. Authors found that Akkermansia was the main bacteria species linked to the SUDD,
since it was inversely correlated with abdominal pain in these patients.
The study on SUDD microbiota are still contradictory and no definite data are available. Thus,
any new study is welcomed. Although this study try to identify some relationship between SUDD
and microbiota, is suffer from too bias to guarantee acceptance.
1. About the inclusion criteria:
a.  the definition of SUDD is not described neither referenced;
b. no description on how the SUDD diagnosis was made was reported;
c. patients with exacerbation of SUDD were enrolled, but it is unclear how this “exacerbation”
was assessed;
d. The severity of abdominal pain was assessed with an arbitrary scale without any validation.
A simple VAS scale would have been much better.
2. About the exclusion criteria:
a. no information is reported about the previous use of systemic antibiotic or probiotics;
b. the “contraindications to the use of rifaximin” have to be clearly listed;
c. the definition “acute complications of diverticular disease during the previous 6 months” is
unclear: are the author talking about acute diverticulitis? Uncomplicated and/or complicated?
And what about the diverticular bleeding?
3. Data about demographics and concomitant medications are lacking;
4. The final study group was too small, since about half of patients were excluded for several
reasons;
5. A control group is lacking: thus, we don’t have any control to confirm the presence of a
different microbiota in  SUDD;
6. Akkermansia was detected in 2 of 12 (16.7%) patients at inclusion, in 7 of 12 (58.3%; p=0.045)
patients at 3 months, and 9 of 12 (75.0% ; p=0.006) patients after 6 months of rifaximin. This
means that Akkermansia appeared during the follow-up, not that it increased during the follow-
up. This is a substantial difference, since increasing or decreasing during the follow-up has to
be assessed by a # Logarithmic scale.
7. As correctly reported by the authors, other studies in SUDD setting found Akkermansia
increased in these patients, with a significant relationship between its abundance and severity of
abdominal pain. Authors have to try to explain the discrepancy between these literature results
and the findings of this study.
Title: Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic
uncomplicated diverticular disease: results from an observational cohort study
Version: 0 Date: 28 Oct 2022
Reviewer's report:
This study assessed the effect of cyclic treatment with rifaximin on the fecal microbiota of SUDD
patients. Authors found that Akkermansia was the main bacteria species linked to the SUDD,
since it was inversely correlated with abdominal pain in these patients.
The study on SUDD microbiota are still contradictory and no definite data are available. Thus,
any new study is welcomed. Although this study try to identify some relationship between SUDD
and microbiota, is suffer from too bias to guarantee acceptance.
1. About the inclusion criteria:
a.  the definition of SUDD is not described neither referenced;
b. no description on how the SUDD diagnosis was made was reported;
c. patients with exacerbation of SUDD were enrolled, but it is unclear how this “exacerbation”
was assessed;
d. The severity of abdominal pain was assessed with an arbitrary scale without any validation.
A simple VAS scale would have been much better.
2. About the exclusion criteria:
a. no information is reported about the previous use of systemic antibiotic or probiotics;
b. the “contraindications to the use of rifaximin” have to be clearly listed;
c. the definition “acute complications of diverticular disease during the previous 6 months” is
unclear: are the author talking about acute diverticulitis? Uncomplicated and/or complicated?
And what about the diverticular bleeding?
3. Data about demographics and concomitant medications are lacking;
4. The final study group was too small, since about half of patients were excluded for several
reasons;
5. A control group is lacking: thus, we don’t have any control to confirm the presence of a
different microbiota in  SUDD;
6. Akkermansia was detected in 2 of 12 (16.7%) patients at inclusion, in 7 of 12 (58.3%; p=0.045)
patients at 3 months, and 9 of 12 (75.0% ; p=0.006) patients after 6 months of rifaximin. This
means that Akkermansia appeared during the follow-up, not that it increased during the follow-
up. This is a substantial difference, since increasing or decreasing during the follow-up has to
be assessed by a # Logarithmic scale.
7. As correctly reported by the authors, other studies in SUDD setting found Akkermansia
increased in these patients, with a significant relationship between its abundance and severity of
abdominal pain. Authors have to try to explain the discrepancy between these literature results
and the findings of this study.
Please review this paper.
user
Title: Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic
uncomplicated diverticular disease: results from an observational cohort study
Version: 0 Date: 28 Oct 2022
Reviewer's report:
This study assessed the effect of cyclic treatment with rifaximin on the fecal microbiota of SUDD
patients. Authors found that Akkermansia was the main bacteria species linked to the SUDD,
since it was inversely correlated with abdominal pain in these patients.
The study on SUDD microbiota are still contradictory and no definite data are available. Thus,
any new study is welcomed. Although this study try to identify some relationship between SUDD
and microbiota, is suffer from too bias to guarantee acceptance.
1. About the inclusion criteria:
a.  the definition of SUDD is not described neither referenced;
b. no description on how the SUDD diagnosis was made was reported;
c. patients with exacerbation of SUDD were enrolled, but it is unclear how this “exacerbation”
was assessed;
d. The severity of abdominal pain was assessed with an arbitrary scale without any validation.
A simple VAS scale would have been much better.
2. About the exclusion criteria:
a. no information is reported about the previous use of systemic antibiotic or probiotics;
b. the “contraindications to the use of rifaximin” have to be clearly listed;
c. the definition “acute complications of diverticular disease during the previous 6 months” is
unclear: are the author talking about acute diverticulitis? Uncomplicated and/or complicated?
And what about the diverticular bleeding?
3. Data about demographics and concomitant medications are lacking;
4. The final study group was too small, since about half of patients were excluded for several
reasons;
5. A control group is lacking: thus, we don’t have any control to confirm the presence of a
different microbiota in  SUDD;
6. Akkermansia was detected in 2 of 12 (16.7%) patients at inclusion, in 7 of 12 (58.3%; p=0.045)
patients at 3 months, and 9 of 12 (75.0% ; p=0.006) patients after 6 months of rifaximin. This
means that Akkermansia appeared during the follow-up, not that it increased during the follow-
up. This is a substantial difference, since increasing or decreasing during the follow-up has to
be assessed by a # Logarithmic scale.
7. As correctly reported by the authors, other studies in SUDD setting found Akkermansia
increased in these patients, with a significant relationship between its abundance and severity of
abdominal pain. Authors have to try to explain the discrepancy between these literature results
and the findings of this study.
assistant