Long-term diosmectite use does not alter the gut microbiota in adults with chronic diarrhea

Kévin Da Silva, Susie Guilly, Florence Thirion, Emmanuelle Le Chatelier, Nicolas Pons, Hugo Roume, Benoît Quinquis, Stanislav D Ehrlich, Nassima Bekkat, Hélène Mathiex-Fortunet, Harry Sokol, Joël Doré, Kévin Da Silva, Susie Guilly, Florence Thirion, Emmanuelle Le Chatelier, Nicolas Pons, Hugo Roume, Benoît Quinquis, Stanislav D Ehrlich, Nassima Bekkat, Hélène Mathiex-Fortunet, Harry Sokol, Joël Doré

Abstract

Background: Diosmectite, a natural colloidal clay, has been used worldwide for a number of approved indications, including the treatment of chronic functional diarrhea. Here, we used high-resolution whole metagenome shotgun sequencing to assess the impact of a 5 weeks administration of diosmectite (3 g/sachet, 3 sachets/day) on the fecal microbiota of 35 adults with functional chronic diarrhea.

Results: Gut microbiota was not impacted by diosmectite administration. In particular, richness remained stable and no microbial species displayed a significant evolution. Segregating patients either by diosmectite response (non responder, early responder, late responder) or by nationality (Great-Britain or Netherlands) yielded the same results.

Conclusion: We concluded that no microbiota-related physiological alterations are expected upon long-term treatment with diosmectite.

Trial registration: Clinicaltrials.gov NCT03045926.

Keywords: Chronic diarrhea; Diosmectite; Gut microbiota; Long-term diosmectite use; Loose stools; Microbiota composition; Shotgun metagenomics; Smecta®; Watery stools.

Conflict of interest statement

NB is employee of IPSEN. HMF is consultant of IPSEN. Other co-authors do not have any competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Bristol stool scale evolution according to visit. P-values associated with Wilcoxon signed-rank test are displayed. Boxes represent the median and interquartile ranges (IQRs) between the first and third quartiles; whiskers represent the lowest or highest values within 1.5 times IQR from the first or third quartiles
Fig. 2
Fig. 2
Microbiota evolution according to visit. A MGS richness evolution according to visit. B Boxplots of Bray–Curtis dissimilarity between MGS abundance at baseline (D-1) and MGS abundance at other time points (D-30, D-14, D8 or D35). P-values associated with Wilcoxon signed-rank test are displayed. Boxes represent the median and interquartile ranges (IQRs) between the first and third quartiles; whiskers represent the lowest or highest values within 1.5 times IQR from the first or third quartiles. C Principal Coordinates Analysis (PCoA) performed on Bray–Curtis dissimilarity matrix computed on MGS abundances. Patients are colored according to visit, and the analysis of similarity between different visits was computed through ANOSIM
Fig. 3
Fig. 3
Phyla distribution evolution. Mean phyla relative abundance along the different time points
Fig. 4
Fig. 4
Early-, late-, and non-responders. A Bristol stool scale evolution across the different time points according to responder subgroups. P-values associated with Wilcoxon signed-rank test are displayed. B Bristol stool scale at baseline (D-1) according to responder subgroups. P-values associated with Mann–Whitney test are displayed. C MGS richness at baseline (D-1) according to responder subgroups. P-values associated with Mann–Whitney test are displayed. Boxes represent the median and interquartile ranges (IQRs) between the first and third quartiles; whiskers represent the lowest or highest values within 1.5 times IQR from the first or third quartiles

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