Title: Unveiling the diagnostic and pro-inflammatory role of Crohn’s disease: insights from
16S-guided discovery and species-specific validation
Version: 1 Date: 14 Feb 2025
Reviewer's report:
The paper investigated the role of Ruminococcus gnavus in Crohn's disease (CD) pathogenesis.
Comments
1. The study used R. gnavus strain ATCC 29149, but it did not address whether this strain was
representative of the strains found in CD patients or if it belonged to a specific clade associated
with disease. Previous studies have shown that R. gnavus exhibits strain-specific effects, with
some strains being pro-inflammatory and others tolerogenic.
2. The study implied a causal role for R. gnavus in CD pathogenesis, but its design
(observational and correlational) cannot establish causality. Previous studies emphasize the need
for experimental validation to determine whether R. gnavus drives disease or is a consequence
of the altered gut environment in CD.
3. The study included 22 patients with active CD, 10 patients with inactive CD, and 32 healthy
controls. This sample size may not be sufficient to capture the full heterogeneity of CD,
especially given the variability in disease presentation and progression.
4. While the random forest model achieved a high AUC (0.938), the authors did not describe
how the model was validated (e.g., cross-validation, independent cohort).
5. The authors focused on R. gnavus but did not discuss the potential roles of other microbial
genera identified. The gut microbiome is generally considered as a complex ecosystem, where
interactions between multiple species may contribute to disease. Furthermore, the study could
not address whether the observed effects of R. gnavus are unique or if other microbes could
compensate for its absence. Functional redundancy in the gut microbiome may exist and disease-
associated microbes may share similar metabolic capabilities.
6. The authors suggest that the identified genera (including R. gnavus) could serve as diagnostic
biomarkers for CD. However, they did not discuss the feasibility of translating these findings
into clinical practice (e.g., sensitivity, specificity, cost-effectiveness).
7. The authors have not investigated whether targeting R. gnavus could be a viable therapeutic
strategy for CD.
Title: Unveiling the diagnostic and pro-inflammatory role of Crohn’s disease: insights from
16S-guided discovery and species-specific validation
Version: 1 Date: 14 Feb 2025
Reviewer's report:
The paper investigated the role of Ruminococcus gnavus in Crohn's disease (CD) pathogenesis.
Comments
1. The study used R. gnavus strain ATCC 29149, but it did not address whether this strain was
representative of the strains found in CD patients or if it belonged to a specific clade associated
with disease. Previous studies have shown that R. gnavus exhibits strain-specific effects, with
some strains being pro-inflammatory and others tolerogenic.
2. The study implied a causal role for R. gnavus in CD pathogenesis, but its design
(observational and correlational) cannot establish causality. Previous studies emphasize the need
for experimental validation to determine whether R. gnavus drives disease or is a consequence
of the altered gut environment in CD.
3. The study included 22 patients with active CD, 10 patients with inactive CD, and 32 healthy
controls. This sample size may not be sufficient to capture the full heterogeneity of CD,
especially given the variability in disease presentation and progression.
4. While the random forest model achieved a high AUC (0.938), the authors did not describe
how the model was validated (e.g., cross-validation, independent cohort).
5. The authors focused on R. gnavus but did not discuss the potential roles of other microbial
genera identified. The gut microbiome is generally considered as a complex ecosystem, where
interactions between multiple species may contribute to disease. Furthermore, the study could
not address whether the observed effects of R. gnavus are unique or if other microbes could
compensate for its absence. Functional redundancy in the gut microbiome may exist and disease-
associated microbes may share similar metabolic capabilities.
6. The authors suggest that the identified genera (including R. gnavus) could serve as diagnostic
biomarkers for CD. However, they did not discuss the feasibility of translating these findings
into clinical practice (e.g., sensitivity, specificity, cost-effectiveness).
7. The authors have not investigated whether targeting R. gnavus could be a viable therapeutic
strategy for CD.
Please review this paper.
user
Title: Unveiling the diagnostic and pro-inflammatory role of Crohn’s disease: insights from
16S-guided discovery and species-specific validation
Version: 1 Date: 14 Feb 2025
Reviewer's report:
The paper investigated the role of Ruminococcus gnavus in Crohn's disease (CD) pathogenesis.
Comments
1. The study used R. gnavus strain ATCC 29149, but it did not address whether this strain was
representative of the strains found in CD patients or if it belonged to a specific clade associated
with disease. Previous studies have shown that R. gnavus exhibits strain-specific effects, with
some strains being pro-inflammatory and others tolerogenic.
2. The study implied a causal role for R. gnavus in CD pathogenesis, but its design
(observational and correlational) cannot establish causality. Previous studies emphasize the need
for experimental validation to determine whether R. gnavus drives disease or is a consequence
of the altered gut environment in CD.
3. The study included 22 patients with active CD, 10 patients with inactive CD, and 32 healthy
controls. This sample size may not be sufficient to capture the full heterogeneity of CD,
especially given the variability in disease presentation and progression.
4. While the random forest model achieved a high AUC (0.938), the authors did not describe
how the model was validated (e.g., cross-validation, independent cohort).
5. The authors focused on R. gnavus but did not discuss the potential roles of other microbial
genera identified. The gut microbiome is generally considered as a complex ecosystem, where
interactions between multiple species may contribute to disease. Furthermore, the study could
not address whether the observed effects of R. gnavus are unique or if other microbes could
compensate for its absence. Functional redundancy in the gut microbiome may exist and disease-
associated microbes may share similar metabolic capabilities.
6. The authors suggest that the identified genera (including R. gnavus) could serve as diagnostic
biomarkers for CD. However, they did not discuss the feasibility of translating these findings
into clinical practice (e.g., sensitivity, specificity, cost-effectiveness).
7. The authors have not investigated whether targeting R. gnavus could be a viable therapeutic
strategy for CD.
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