Smecta*60 Sachets. A New Step in Treating Diarrhoea -Powder for Oral Suspension.

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Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528:262–6. The IGC has been previously clustered into 1438 MetaGenomic Species (MGS; clusters of > 500 co-abundant genes belonging to the same microbial species) [ 26]. Taxonomical annotation of MGS was performed using an in-house pipeline. First, all genes are aligned on public databases (ncbi, wgs) [ 37] using blastn (version 2.7.1, task = megablast, word_size = 16) [ 38]. The 20 best hits for each gene were kept. A species-level assignment was given if > 50% of the genes matched the RefSeq reference genome of a given species, with a mean identity ≥ 95% and mean gene length coverage ≥ 90%. The remaining MGS were assigned to a higher taxonomic level (genus to superkingdom), if > 50% of their genes had the same annotation. Relative abundance of an MGS was computed as the mean abundance of its 50 ‘marker’ genes (that is, the genes that correlate the most altogether in terms of abundance). If less than 10% of ‘marker’ genes were seen in a sample, the abundance of the MGS was set to 0. Relative abundances at higher taxonomical ranks were computed as the sum of the MGS that belong to a given taxa. Gene and MGS richness Rateau et al. [ 20] described the anti-diarrhoeal effects of DS related to increased chloride and magnesium absorption in the rabbit ileal mucosa infected with enterotoxigenic E. coli. These effects were postulated to be due to the inhibition of mucolysis or to the attenuation of damage to the luminal surface of the intestinal mucosa. In addition, DS reduced interleukin-1β (IL-1β) secretion and decreased neutrophil infiltration and monocyte activation, which both contributed to a reduction of the antigenic load in hapten-induced colitis in the rat [ 4]. Since IL-1β induces chloride secretion [ 21], it is possible that this anti-inflammatory effect contributes to the antidiarrhoeal mechanism of DS. However, such a mechanism cannot explain the effects observed with RV diarrhoea, which is not associated with intestinal inflammation. Diosmectite is a well-defined multilamellar argillaceous compound recommended for the management of several GI diseases in adults and children 17, 18. At the time of writing, there are no empirical data on the efficacy of diosmectite in patients with COVID-19, thus clinical recommendations for its use in these patients are based on an inferred clinical rationale.

Acute diarrhoea is one of the leading causes of morbidity worldwide [ 1]. The annual rate of diarrhoea among adults in Western Europe and the United States averages about one episode per person per year [ 2– 4]. Episodes are usually brief, not life-threatening and most often self-limited but symptoms can be disturbing and incapacitating. Urgency, loose stools, abdominal discomfort, and inconvenience such as loss of faecal continence make it an unpleasant and distressing condition. It is commonly recognized that these symptoms lead to substantial costs for society as it is estimated that half of the episodes are related to missed workdays [ 5, 6]. Rotavirus (RV) induces diarrhoea through a sequence of enterotoxic and cytotoxic effects. The former are NSP4-dependent, induce calcium-dependent chloride secretion and involve oxidative stress. Diosmectite (DS) is a natural clay that has been recommended as an active therapy for diarrhoea, but the mechanism of its effect is not clear. Electrical parameters may be used to measure the direct enterotoxic and cytotoxic effects in polar epithelial intestinal cells. To investigate the effects of DS on RV-induced enterotoxic and cytotoxic damage. Caco-2 cells were used as a model of RV infection to evaluate chloride secretion, epithelial integrity, oxidative stress and viral infectivity in Ussing chambers. Results

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de Gunzburg J, Ghozlane A, Ducher A, Le Chatelier E, Duval X, Ruppé E, et al. Protection of the human gut microbiome from antibiotics. J Infect Dis. 2018;217:628–36. We further looked for diosmectite impact at the species level. Considering the 450 MGS that were present in more than 10% of samples, the AUC analysis showed that 18 MGS had a different evolution before and after treatment ( p≤0.05, Wilcoxon signed-rank test). Among them, only 4 and 5 MGS had a significantly different abundance in at least one of the three time points before treatment or during treatment, respectively (p≤0.05, Friedman test). The five MGS whose abundance changed during the treatment had low prevalence at D-1 (32%±0.1, see Additional file 1, Supplementary Fig.2) and accounted for only 0.3%±0.5 of the total microbiota. Moreover, we found the same number of MGS ( n=35) whose abundance changed significantly before the treatment (at D-30, D-14 or D-1, Friedman test, p≤0.05), or during the treatment (at D-1, D8, D35, Friedman test, p≤0.05), suggesting even more random variations instead of an effect of the treatment. Additionally, after correction for multiple testing only one MGS was significantly altered before the treatment, and none during the treatment. De Marco G, Bracale I, Buccigrossi V, Bruzzese E, Canani RB, Polito G, et al. Rotavirus induces a biphasic enterotoxic and cytotoxic response in human-derived intestinal enterocytes, which is inhibited by human immunoglobulins. J Infect Dis. 2009;200:813–9. In our experimental approach, we separately investigated the effects induced by DS on the enterotoxic and cytotoxic pathways of RV-induced diarrhoea in a human model. Our results indicate that DS effectively reduces the intensity of RV infection of intestinal epithelial cells and inhibits RV-induced chloride secretion in Caco-2 cell monolayers. This effect is the result of an interaction between DS and RV, whereby the adsorption of RV particles by DS effectively reduces the infection load on epithelial cells. The subsequent reduction of chloride secretion observed in our in vitro model provides a plausible explanation for the reduction of stool output in children with acute gastroenteritis treated with DS [ 10].

The clinical trial was a prospective, open label, non-comparative, multi-center, international study with chronic treatment of diosmectite (Smecta®, 3 g) TID over 5 weeks, whose first purpose was to assess the level of elemental impurities (e.g. lead, arsenic, cadmium) in blood and urine samples after chronic administration of diosmectite. The aim of this ancillary study was to assess the bowel microbiota composition, stools consistency and frequency after chronic administration of diosmectite in subjects with chronic functional diarrhea. Guarino A, Lo Vecchio A, Pirozzi MR. Clinical role of diosmectite in the management of diarrhea. Expert Opin Drug Metab Toxicol. 2009;5:433–40. Mahraoui L, Heyman M, Plique O, Droy-Lefaix MT, Desjeux JF. Apical effect of diosmectite on damage to the intestinal barrier induced by basal tumour necrosis factor-alpha. Gut. 1997;40:339–43. Clark KJ, Sarr AB, Grant PG, Phillips TD, Woode GN. In vitro studies on the use of clay, clay minerals and charcoal to adsorb bovine rotavirus and bovine coronavirus. Vet Microbiol. 1998;63:137–46.This study was conducted in compliance with the protocol, in accordance with the International Conference on Harmonisation Good Clinical Practice (CPMP/ICH 135/35) together with such other good clinical practice requirements and the ethical principles that have their origin in the Declaration of Helsinki, as well as with all currently applicable laws and regulations of the country where the study was conducted. Informed consent was obtained from all subjects during the screening period. The trial was registered with Clinicaltrials.gov, number NCT03045926 on the 08/02/2017 ( https://clinicaltrials.gov/ct2/show/NCT03045926). A fluorescence focus assay in the MA104 cell monolayers was used to determine the viral titre, expressed as focus-forming units per millilitre of virus (FFU/ml). Briefly, MA104 cells were grown in 8-chamber slides (Lab-Tek chamber Slide, Nunc Inc, USA) and then infected with supernatants from the Caco-2 infection experiments. After viral absorption, the cells were fixed in methanol and probed with fluorescein isothiocyanate (FITC) conjugated anti-RV antibody (Abcam, ab31435). Fluorescence foci were counted individually on a Nikon Eclipse 80i epifluorescence microscope (FITC filter). The viral titre was calculated from the average number of foci per well adjusted for well volume and expressed as FFU/ml. As a negative control, a mixture of titanium dioxide, maltodextrin and glucose monohydrate was used (TMG). Virus strain and Caco-2 cell infection protocol Infection with RV was performed with multiplicities of infection (MOI) of 25 for 2 h; next, the cell monolayers were mounted in Ussing chambers (Physiological Instruments, San Diego, CA). The following electrical parameters were measured at different time points after infection: transepithelial potential difference ( PD), short-circuit current ( Isc), and tissue ionic conductance ( G). Isc is expressed as microamperes per square centimetre (μA/cm 2), G is expressed as millisiemens per square centimetre (mS/cm 2), and PD is expressed as millivolts (mV). An increase in PD indicates chloride secretion and provides a precise evaluation of enterotoxic effects, whereas an increase in G quantitatively correlates with epithelial damage. Transepithelial electrical resistance measurements Diosmectite (brand names Smecta, Smecdral) is a natural silicate of aluminium and magnesium used as an intestinal adsorbent in the treatment of several gastrointestinal diseases, including infectious and non-infectious acute and chronic diarrhoea, including irritable bowel syndrome diarrhea subtype. Other uses include: chronic diarrhea caused by radiation-induced, chemotherapy-induced, and HIV/AIDS-associated chronic diarrhea. [1] There is increasing evidence that the NF-kappaB pathway is a central signaling pathway for the SARS-CoV-2 infection-induced pro-inflammatory cytokine/chemokine response, and that inhibition of NF-kappaB has the potential to inhibit both virus- and LPS-induced cytokine storm 30. Diosmectite was able to prevent both NF-kappaB activation and CXCL10 secretion because of its ability to trap viral particles, ther

Rotavirus (RV) is the commonest aetiological agent of AGE in children and induces severe watery diarrhoea. Its severity is related to its mechanism of action, namely, a sequence of time-related mechanisms leading to secretory diarrhoea and intestinal epithelial damage [ 12]. In the early phase of infection, RV directly induces chloride and water secretion in the intestinal lumen through the enterotoxic effects of the non-structural viral protein NSP4. This increases the intracellular Ca 2+ concentration and triggers electrogenic chloride secretion [ 12, 13, 14]. As recently reported, oxidative stress is a key mechanism in the enterotoxic effect induced by RV [ 14]. Following early ion secretion, RV infection results in severe damage to the structure of villi, with the disruption of epithelial integrity [ 15]. We validated this method and confirmed that MGS were not impacted by diosmectite treatment using another approach (non-parametric tests for longitudinal data, see Supplementary Fig. 3, Additional File 1, Supplementary Table 1 in Additional File 2). Romano J, Kromrey JD, Coraggio J, Skowronek J. Appropriate statistics for ordinal level data: Should we really be using t-test and Cohen’sd for evaluating group differences on the NSSE and other surveys? Annu Meet Florida Assoc Institutional Res. 2006;177:1–3. In the ITT population ( n = 329), the median [range] time to recovery was significantly shorter in the diosmectite group (53.8 hours [3.7–167.3]) than in the placebo group (69.0 hours [2.0–165.2]) when tested with Wilcoxon's test ( P = .0294). The difference between the two groups was 15.2 hours. The statistical significance of this effect was also evidenced by the post hoc analysis using the time-to-event Gehan-Wilcoxon test considering censored data: 56.3 hours [47.7– 68.0] in the diosmectite group versus 72.2 [63.3– 82.0] hours in the placebo group ( P = .0291). Chang F-Y, Lu C-L, Chen C-Y, Luo J-C. Efficacy of dioctahedral smectite in treating patients of diarrhea-predominant irritable bowel syndrome. J Gastroenterol Hepatol Australia. 2007;22:2266–72.Considering its importance in the microbiota composition, another limit of the study is the absence of data related to diet apart from the exclusion criteria (artificial feeding or subjects eating shellfish more than two times a week, see Methods).