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

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The same assay protocol was used to evaluate the absorptive effect of DS on NSP4. Briefly, 100 mg/ml DS was incubated with medium alone or in the presence of NSP4 at different doses (50, 100 and 200 ng/ml) for 1 h at 37 °C. The slides were probed with an anti-NSP4 antibody and then with a fluorescein isothiocyanate (FITC) conjugated anti-rabbit antibody. Then, the slides were examined using a Nikon Eclipse 80i epifluorescence microscope (FITC filter). The images were analysed using the NIS Elements D imaging software. RV positive cell staining

Ousingsawat J, Mirza M, Tian Y, Roussa E, Schreiber R, Cook DI, et al. Rotavirus toxin NSP4 induces diarrhea by activation of TMEM16A and inhibition of Na+ absorption. Pflügers Arch Eur J Physiol. 2011;461:579–89. Thirty-five adults subjects were enrolled, 20 males and 15 females, whose country of residence was Netherlands (NLD; n = 12) or Great Britain (GRB; n = 23). The inclusion criteria were: male or female, between 18 and 60 years old, BMI between 19 and 32 kg/m 2, minimum body weight of 50 kg. They had functional chronic diarrhea defined according to the Rome IV criteria with loose or watery stools according to Bristol stool scale (BSS) grade 6 and 7, occurring in at least 75% of stools for the last 3 months (with symptoms onset at least 6 months before diagnosis), with or without pain [ 24]. Subjects with history of suspected organic or drug induced cause to chronic diarrhea were excluded as well as antibiotic, metformin and/or Proton Pump Inhibitor intake within the month prior to baseline visit or during the study. The inclusion took place from 24 August 2016 to 9 May 2017, in the Netherlands (PRA Healthy Sciences, Groningen, 9728NZ), and in the United Kingdom (MAC Clinical Resarch Limited, Manchester, M13 9NQ). Treatment Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol England. 1990;215:403–10. 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]. 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 {"type":"clinical-trial","attrs":{"text":"NCT03045926","term_id":"NCT03045926"}}NCT03045926 on the 08/02/2017 (https://clinicaltrials.gov/ct2/show/ {"type":"clinical-trial","attrs":{"text":"NCT03045926","term_id":"NCT03045926"}}NCT03045926).The clinical trial was a prospective, open label, non-comparative, multi-center, international study with chronic treatment of diosmectite (Smecta®, 3g) TID over 5weeks, 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, Vecchio A. Lo, Pirozzi MR. Clinical role of diosmectite in the management of diarrhea. Expert Opin Drug Metab Toxicol. 2009;5:433–40. Particularly, incidence of new nausea episodes during the study was observed in 4.2% (7/166) of the patients in the diosmectite group and 3.7% (6/163) in the placebo group. Incidence of abdominal pain episodes was observed in 2.4% (4/166) of the patients in the diosmectite group and 8.6% (14/163) in the placebo group. Finally, incidence of anal irritation episodes was observed in 12.6% (21/166) of the patients in the diosmectite group and 29.4% (48/163) in the placebo group.

Vieira-Silva S, Falony G, Belda E, Nielsen T, Aron-Wisnewsky J, Chakaroun R, et al. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis. Nature England. 2020;581:310–5. The study included outpatient males and nonpregnant women aged 18 to 65 years in 23 primary and secondary care centres in Tunisia. The development of diarrhea in patients with COVID-19 may naturally prompt the use of antidiarrheal agents, but caution has been recommended with respect to the use of agents that slow intestinal motility 12. These agents extend transit time and may delay the clearance of the SARS-CoV-2 pathogen from the gut 12, 13. Thus, antimotility drugs have the potential to prolong the course of SARS-CoV-2 infection and increase the risk of a more severe COVID-19 disease course 12. Based on this theoretical rationale, it has been highlighted that it may be relevant to consider use of antidiarrheal agents with a mode of action that does not delay intestinal transit time 12. Relevant drug classes in patients with diarrhea include antisecretory agents with inhibitory actions on enkephalinase and adsorbents that have the potential to bind digestive mucus and toxins, as well as reduce water loss 12. Indeed, recommendations for the use of the adsorbent dioctahedral smectite (diosmectite) have appeared in a number of local protocols and national guidelines for the management of GI symptoms in patients with COVID-19 14, 15, 16. 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.Median [range] time from first sachet intake to the last watery stool was 20.5 hours [0.0–160.8] in the diosmectite group and 23.0 hours [0.0–223.8] in the placebo group ( P = .569). The median number of stools per 12-hour period decreased from 3 at baseline to 1 at the 36–48h period onwards with a significant difference in favour of diosmectite group at the 72–84h period ( P = .016). The median number of watery stools decreased from 2 at baseline to 0 at the 12–24h period onwards (N.S). If you bring more than 3 months supply with you, or get more medicine posted to you, it will be taken away. Exceptional circumstances 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 Buccigrossi V, Russo C, Guarino A, de Freitas MB, Guarino A. Mechanisms of antidiarrhoeal effects by diosmectite in human intestinal cells. Gut Pathog. 2017;9:23.

Diosmectite reduced the expression of NSP4 and oxidative stress, resulting in a strong inhibition of chloride secretion. Preincubating RV with DS reduced the cytotoxic effect. Finally, the viral load was reduced by DS but not by control clay. This result suggests that DS specifically affects the early events of RV infection protecting the enterocyte, whereas it does not restore already-established cell damage. Conclusion Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541–6 England. Hu C, Song J, You Z, Luan Z, Li W. Zinc oxide-montmorillonite hybrid influences diarrhea, intestinal mucosal integrity, and digestive enzyme activity in weaned pigs. Biol Trace Elem Res United States. 2012;149:190–6. Despite significantly shorter time to recovery in the diosmectite group, the proportions of patients achieving recovery were similar in both groups at the end of the study. This is explained by acute watery diarrhoea being self-resolving within seven days.Chang F-Y, Lu C-L. Irritable bowel syndrome in the 21st century: perspectives from Asia or South-east Asia. J Gastroenterol Hepatol Australia. 2007;22:4–12. Among the 35 participants, five were missing one or several samples (maximum missing samples: 3 at D-14), leading to a total of 170 samples available for the analysis. DNA extraction and sequencing After a screening period of up to 6weeks including a baseline assessment, each subject was dosed with diosmectite TID over 5weeks (Day 1 to Day 35). Feces samples were collected at screening phase (D-30, D-14), at baseline visit (D-1), and over the treatment period (D8, D35). Collection was performed using a kit provided by INRAE using a stabilizing solution (RNAlater®; ThermoFisher Scientific, Waltham, US) (SOP05_V2 from the International Human Microbiome Standards, IHMS) [ 31] allowing samples to be preserved within 24h to 7days at room temperature before to be handled by laboratory. Dupont C, Foo JLK, Garnier P, Moore N, Mathiex-Fortunet H, Salazar-Lindo E. Oral diosmectite reduces stool output and diarrhea duration in children with acute watery diarrhea. Clin Gastroenterol Hepatol. 2009;7:456–62.