RESUMO
BACKGROUND/AIMS: Five million people currently live with Crohn's disease (CD) or ulcerative colitis, the two major forms of inflammatory bowel disease. Available treatments frequently result in side effects that compromise the immune health of the patient. Consequently, alternative therapies that cause fewer systemic effects are needed. Dioctahedral smectite clays have been utilized to treat medical conditions, including diarrheal and enteric disease. Herein, we report the ability of a refined dioctahedral smectite (NovaSil, NS) to sorb inflammatory proteins and reduce inflammation in a TNBS (2,4,6-trinitrobenzenesulfonic acid) mouse model of CD. We also investigated whether NS could rescue gut microbial diversity in TNBS-induced mice. METHODS: ELISA, X-ray diffraction, and transmission electron microscopy were employed to characterize the NS-cytokine interaction in vitro. A TNBS mouse colitis model was utilized to study the efficacy of NS supplementation for 4 weeks. The three treatment groups included control, TNBS, and TNBS + NS. DNA was extracted from feces and sorted for bacterial phylogenetic analysis. RESULTS: Results suggest that NS binds TNFα in vitro. In TNBS-treated mice, supplementation with NS significantly reduced weight loss, and serum proinflammatory cytokine levels (IL-2, IL-6, and IL-12, TNFα, IFNγ) compared with the TNBS group. TNBS-treated mice demonstrated a significant reduction in gut microbiota species richness when compared with the TNBS + NS group and control group. CONCLUSIONS: NovaSil mitigated the effects of TNBS-induced colitis based on reduction in systemic markers of inflammation, significant improvement in weight gain, and intestinal microbial profile.
Assuntos
Silicatos de Alumínio/farmacologia , Anti-Inflamatórios/farmacologia , Colite/prevenção & controle , Colo/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Silicatos/farmacologia , Silicatos de Alumínio/química , Animais , Anti-Inflamatórios/química , Bactérias/classificação , Bactérias/isolamento & purificação , Argila , Colite/sangue , Colite/induzido quimicamente , Colite/microbiologia , Colo/metabolismo , Colo/microbiologia , Cristalografia por Raios X , Citocinas/sangue , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Fármacos Gastrointestinais/química , Mediadores da Inflamação/sangue , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Difração de Pó , Ribotipagem , Silicatos/química , Fatores de Tempo , Ácido Trinitrobenzenossulfônico , Aumento de Peso/efeitos dos fármacosRESUMO
Recently, an association between childhood growth stunting and aflatoxin (AF) exposure has been identified. In Ghana, homemade nutritional supplements often consist of AF-prone commodities. In this study, children were enrolled in a clinical intervention trial to determine the safety and efficacy of Uniform Particle Size NovaSil (UPSN), a refined calcium montmorillonite known to be safe in adults. Participants ingested 0.75 or 1.5 g UPSN or 1.5 g calcium carbonate placebo per day for 14 days. Hematological and serum biochemistry parameters in the UPSN groups were not significantly different from the placebo-controlled group. Importantly, there were no adverse events attributable to UPSN treatment. A significant reduction in urinary metabolite (AFM1) was observed in the high-dose group compared with placebo. Results indicate that UPSN is safe for children at doses up to 1.5 g/day for a period of 2 weeks and can reduce exposure to AFs, resulting in increased quality and efficacy of contaminated foods.