Reviewer's report
Title:Effect of a multispecies probiotic supplement on the quantities of irritable
bowel syndrome-related intestinal microbial phylotypes
Version: 1Date:4 February 2010
Reviewer: Robin Spiller
Reviewer's report:
This is a microbiological assessment using quantitative PCR for quantifying
selected faecal bacterial phylotypes in stool samples collected during a six month
trial of probiotics in patients with the irritable bowel syndrome (IBS), the clinical
results of which were published in 2005. The study showed an improvement,
most obvious after 6 months with a 42% improvement in a Total Symptom Score
which summed scores for pain, distension, flatulence and borborygmi. The
greatest effect was seen on borborygmi. Owning to the intensive and expensive
nature of the work, previous studies on the faecal microbiota in IBS have had
small numbers and these further observations on 42 subjects in a randomised
control trial are welcome. Problems with previous studies include the
heterogeneity of IBS and the difficulty in controlling diet, transit and the use of
antibiotics all of which influence the microbiota. The other problem with previous
studies is the use of poorly characterised IBS patients, not distinguishing the
diarrhoea subtype who have fast transit from the constipated ones who generally
have slower transit.
Subjects in this study received 8-9 x 109 CFU/day of a multi-species probiotic
containing Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium
freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99. A quantitative
real time PCR reaction was used to assess abundance of 8 bacterial phylotypes.
These phylotypes were chosen on the basis of previous isolated reports
suggesting that they would be altered in IBS. Note that these different studies did
not identify the same organisms so it is obvious that there is no one single
bacterial abnormality in IBS.
The results of the present study are clearly described and the previous report
suggests that study was carried out to a high standard. However when it comes
to the IBS subtypes, the numbers in each group are rather small and there is
some imbalance with for example more constipated subjects in the placebo
group than the treatment arm.
The main findings were a significant decrease in R. Torques 94% phylotypes in
the probiotic treatment at 6 months while C. Thermosuccinognes 85% phylotypes
were significantly elevated at both 3 and 6 months. Within the small IBS-D
subgroup (N=11 and 8 on treatment and placebo respectively) there was an
increase in R. Torques 93% in the probioitc group at 3 months but not at 6. The
discussion is quite limited as to what the significance of these findings are which
indeed are unclear. The statement that the alterations showed a trend towards a
“healthier” microbiota is little difficult to understand. It is unclear what the criteria
for health are.
Major Comments
1. This study choose to study bacteria that have been reported as being
abnormal in IBS which is a reasonable start although as already pointed out
there is not much consistency in previous studies. Unfortunately however there is
no driving underlying hypothesis or suggested mechanism. It is of course unclear
whether bacteria which have been identified as being abnormal in IBS in one
study but not repeated in the second are indeed just chance findings or due to
differences in the many variable affecting fecal bacteria.
2. This study would be of greater interest if the authors had been able to show
whether the organisms that they have shown the change have any distinct
metabolic or other functions. Can they at least discuss this.
3. It is also unclear how reproducible these findings are and although the
statistics were designed to prevent this, it is unclear whether this is in fact a
chance finding. Obviously reproduction of the result in a further trial would
considerably increase confidence in its meaningfulness.
4. It is also unclear to me the logic of considering just IBS-D in this sub analysis
whereas in fact the clinical benefits were not seen in this group but rather in the
IBS-C group.
5. I think further studies should attempt to demonstrate reproducibility of the
findings.
6. Future studies should also carefully document the diet an attempt to control it
during the study, as changes in the diet may well alter the microbiota. Indeed
probiotic trials often do require changes in diet as subjects are asked to avoid
other probiotics and may well substitute other foods which may themselves alter
the microbiota.
7. Future studies should also try to link functional assessments to see if these
could be correlated with the changes in the microbiota. Thus for example, a
recent study looked at transit and showed that the probiotic treatment
accelerated, it thereby giving a plausible mechanism of its benefit. 1
Reference List
1. Agrawal A, Houghton LA, Morris J, Reilly B, Guyonnet D, Goupil FN,
Schlumberger A, Jakob S, Whorwell PJ. Clinical trial: the effects of a fermented
milk product containing Bifidobacterium lactis DN-173-010 on abdominal
distension and gastrointestinal transit in irritable bowel syndrome with
constipation. Aliment Pharmacol Ther 2008.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Effect of a multispecies probiotic supplement on the quantities of irritable
bowel syndrome-related intestinal microbial phylotypes
Version: 1Date:4 February 2010
Reviewer: Robin Spiller
Reviewer's report:
This is a microbiological assessment using quantitative PCR for quantifying
selected faecal bacterial phylotypes in stool samples collected during a six month
trial of probiotics in patients with the irritable bowel syndrome (IBS), the clinical
results of which were published in 2005. The study showed an improvement,
most obvious after 6 months with a 42% improvement in a Total Symptom Score
which summed scores for pain, distension, flatulence and borborygmi. The
greatest effect was seen on borborygmi. Owning to the intensive and expensive
nature of the work, previous studies on the faecal microbiota in IBS have had
small numbers and these further observations on 42 subjects in a randomised
control trial are welcome. Problems with previous studies include the
heterogeneity of IBS and the difficulty in controlling diet, transit and the use of
antibiotics all of which influence the microbiota. The other problem with previous
studies is the use of poorly characterised IBS patients, not distinguishing the
diarrhoea subtype who have fast transit from the constipated ones who generally
have slower transit.
Subjects in this study received 8-9 x 109 CFU/day of a multi-species probiotic
containing Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium
freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99. A quantitative
real time PCR reaction was used to assess abundance of 8 bacterial phylotypes.
These phylotypes were chosen on the basis of previous isolated reports
suggesting that they would be altered in IBS. Note that these different studies did
not identify the same organisms so it is obvious that there is no one single
bacterial abnormality in IBS.
The results of the present study are clearly described and the previous report
suggests that study was carried out to a high standard. However when it comes
to the IBS subtypes, the numbers in each group are rather small and there is
some imbalance with for example more constipated subjects in the placebo
group than the treatment arm.
The main findings were a significant decrease in R. Torques 94% phylotypes in
the probiotic treatment at 6 months while C. Thermosuccinognes 85% phylotypes
were significantly elevated at both 3 and 6 months. Within the small IBS-D
subgroup (N=11 and 8 on treatment and placebo respectively) there was an
increase in R. Torques 93% in the probioitc group at 3 months but not at 6. The
discussion is quite limited as to what the significance of these findings are which
indeed are unclear. The statement that the alterations showed a trend towards a
“healthier” microbiota is little difficult to understand. It is unclear what the criteria
for health are.
Major Comments
1. This study choose to study bacteria that have been reported as being
abnormal in IBS which is a reasonable start although as already pointed out
there is not much consistency in previous studies. Unfortunately however there is
no driving underlying hypothesis or suggested mechanism. It is of course unclear
whether bacteria which have been identified as being abnormal in IBS in one
study but not repeated in the second are indeed just chance findings or due to
differences in the many variable affecting fecal bacteria.
2. This study would be of greater interest if the authors had been able to show
whether the organisms that they have shown the change have any distinct
metabolic or other functions. Can they at least discuss this.
3. It is also unclear how reproducible these findings are and although the
statistics were designed to prevent this, it is unclear whether this is in fact a
chance finding. Obviously reproduction of the result in a further trial would
considerably increase confidence in its meaningfulness.
4. It is also unclear to me the logic of considering just IBS-D in this sub analysis
whereas in fact the clinical benefits were not seen in this group but rather in the
IBS-C group.
5. I think further studies should attempt to demonstrate reproducibility of the
findings.
6. Future studies should also carefully document the diet an attempt to control it
during the study, as changes in the diet may well alter the microbiota. Indeed
probiotic trials often do require changes in diet as subjects are asked to avoid
other probiotics and may well substitute other foods which may themselves alter
the microbiota.
7. Future studies should also try to link functional assessments to see if these
could be correlated with the changes in the microbiota. Thus for example, a
recent study looked at transit and showed that the probiotic treatment
accelerated, it thereby giving a plausible mechanism of its benefit. 1
Reference List
1. Agrawal A, Houghton LA, Morris J, Reilly B, Guyonnet D, Goupil FN,
Schlumberger A, Jakob S, Whorwell PJ. Clinical trial: the effects of a fermented
milk product containing Bifidobacterium lactis DN-173-010 on abdominal
distension and gastrointestinal transit in irritable bowel syndrome with
constipation. Aliment Pharmacol Ther 2008.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Effect of a multispecies probiotic supplement on the quantities of irritable
bowel syndrome-related intestinal microbial phylotypes
Version: 1Date:4 February 2010
Reviewer: Robin Spiller
Reviewer's report:
This is a microbiological assessment using quantitative PCR for quantifying
selected faecal bacterial phylotypes in stool samples collected during a six month
trial of probiotics in patients with the irritable bowel syndrome (IBS), the clinical
results of which were published in 2005. The study showed an improvement,
most obvious after 6 months with a 42% improvement in a Total Symptom Score
which summed scores for pain, distension, flatulence and borborygmi. The
greatest effect was seen on borborygmi. Owning to the intensive and expensive
nature of the work, previous studies on the faecal microbiota in IBS have had
small numbers and these further observations on 42 subjects in a randomised
control trial are welcome. Problems with previous studies include the
heterogeneity of IBS and the difficulty in controlling diet, transit and the use of
antibiotics all of which influence the microbiota. The other problem with previous
studies is the use of poorly characterised IBS patients, not distinguishing the
diarrhoea subtype who have fast transit from the constipated ones who generally
have slower transit.
Subjects in this study received 8-9 x 109 CFU/day of a multi-species probiotic
containing Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium
freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99. A quantitative
real time PCR reaction was used to assess abundance of 8 bacterial phylotypes.
These phylotypes were chosen on the basis of previous isolated reports
suggesting that they would be altered in IBS. Note that these different studies did
not identify the same organisms so it is obvious that there is no one single
bacterial abnormality in IBS.
The results of the present study are clearly described and the previous report
suggests that study was carried out to a high standard. However when it comes
to the IBS subtypes, the numbers in each group are rather small and there is
some imbalance with for example more constipated subjects in the placebo
group than the treatment arm.
The main findings were a significant decrease in R. Torques 94% phylotypes in
the probiotic treatment at 6 months while C. Thermosuccinognes 85% phylotypes
were significantly elevated at both 3 and 6 months. Within the small IBS-D
subgroup (N=11 and 8 on treatment and placebo respectively) there was an
increase in R. Torques 93% in the probioitc group at 3 months but not at 6. The
discussion is quite limited as to what the significance of these findings are which
indeed are unclear. The statement that the alterations showed a trend towards a
“healthier” microbiota is little difficult to understand. It is unclear what the criteria
for health are.
Major Comments
1. This study choose to study bacteria that have been reported as being
abnormal in IBS which is a reasonable start although as already pointed out
there is not much consistency in previous studies. Unfortunately however there is
no driving underlying hypothesis or suggested mechanism. It is of course unclear
whether bacteria which have been identified as being abnormal in IBS in one
study but not repeated in the second are indeed just chance findings or due to
differences in the many variable affecting fecal bacteria.
2. This study would be of greater interest if the authors had been able to show
whether the organisms that they have shown the change have any distinct
metabolic or other functions. Can they at least discuss this.
3. It is also unclear how reproducible these findings are and although the
statistics were designed to prevent this, it is unclear whether this is in fact a
chance finding. Obviously reproduction of the result in a further trial would
considerably increase confidence in its meaningfulness.
4. It is also unclear to me the logic of considering just IBS-D in this sub analysis
whereas in fact the clinical benefits were not seen in this group but rather in the
IBS-C group.
5. I think further studies should attempt to demonstrate reproducibility of the
findings.
6. Future studies should also carefully document the diet an attempt to control it
during the study, as changes in the diet may well alter the microbiota. Indeed
probiotic trials often do require changes in diet as subjects are asked to avoid
other probiotics and may well substitute other foods which may themselves alter
the microbiota.
7. Future studies should also try to link functional assessments to see if these
could be correlated with the changes in the microbiota. Thus for example, a
recent study looked at transit and showed that the probiotic treatment
accelerated, it thereby giving a plausible mechanism of its benefit. 1
Reference List
1. Agrawal A, Houghton LA, Morris J, Reilly B, Guyonnet D, Goupil FN,
Schlumberger A, Jakob S, Whorwell PJ. Clinical trial: the effects of a fermented
milk product containing Bifidobacterium lactis DN-173-010 on abdominal
distension and gastrointestinal transit in irritable bowel syndrome with
constipation. Aliment Pharmacol Ther 2008.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
assistant