RESUMO
BACKGROUND: Oral iron supplementation causes gastrointestinal side effects. Short-term alterations in dietary iron exacerbate inflammation and alter the gut microbiota, in murine models of colitis. Patients typically take supplements for months. We investigated the impact of long-term changes in dietary iron on colitis and the microbiome in mice. METHODS: We fed mice chow containing differing levels of iron, reflecting deficient (100 ppm), normal (200 ppm), and supplemented (400 ppm) intake for up to 9 weeks, both in absence and presence of dextran sodium sulphate (DSS)-induced chronic colitis. We also induced acute colitis in mice taking these diets for 8 weeks. Impact was assessed (i) clinically and histologically, and (ii) by sequencing the V4 region of 16S rRNA. RESULTS: In mice with long-term changes, the iron-deficient diet was associated with greater weight loss and histological inflammation in the acute colitis model. Chronic colitis was not influenced by altering dietary iron however there was a change in the microbiome in DSS-treated mice consuming 100 ppm and 400 ppm iron diets, and control mice consuming the 400 ppm iron diet. Proteobacteria levels increased significantly, and Bacteroidetes levels decreased, in the 400 ppm iron DSS group at day-63 compared to baseline. CONCLUSIONS: Long-term dietary iron alterations affect gut microbiota signatures but do not exacerbate chronic colitis, however acute colitis is exacerbated by such dietary changes. More work is needed to understand the impact of iron supplementation on IBD. The change in the microbiome, in patients with colitis, may arise from the increased luminal iron and not simply from colitis.
Assuntos
Colite/metabolismo , Sobrecarga de Ferro/fisiopatologia , Ferro/metabolismo , Anemia Ferropriva , Animais , Bactérias/genética , Colite/fisiopatologia , Colo/patologia , Sulfato de Dextrana/farmacologia , Dieta , Suplementos Nutricionais/efeitos adversos , Modelos Animais de Doenças , Disbiose/etiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Inflamação , Doenças Inflamatórias Intestinais/patologia , Ferro da Dieta/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Microbiota , RNA Ribossômico 16S/genéticaRESUMO
Inflammatory bowel disease (IBD) is associated with anaemia and oral iron replacement to correct this can be problematic, intensifying inflammation and tissue damage. The intestinal microbiota also plays a key role in the pathogenesis of IBD, and iron supplementation likely influences gut bacterial diversity in patients with IBD. Here, we assessed the impact of dietary iron, using chow diets containing either 100, 200 or 400 ppm, fed ad libitum to adult female C57BL/6 mice in the presence or absence of colitis induced using dextran sulfate sodium (DSS), on (i) clinical and histological severity of acute DSS-induced colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. Increasing or decreasing dietary iron concentration from the standard 200 ppm exacerbated both clinical and histological severity of DSS-induced colitis. DSS-treated mice provided only half the standard levels of iron ad libitum (i.e. chow containing 100 ppm iron) lost more body weight than those receiving double the amount of standard iron (i.e. 400 ppm); p<0.01. Faecal calprotectin levels were significantly increased in the presence of colitis in those consuming 100 ppm iron at day 8 (5.94-fold) versus day-10 group (4.14-fold) (p<0.05), and for the 400 ppm day-8 group (8.17-fold) versus day-10 group (4.44-fold) (p<0.001). In the presence of colitis, dietary iron at 400 ppm resulted in a significant reduction in faecal abundance of Firmicutes and Bacteroidetes, and increase of Proteobacteria, changes which were not observed with lower dietary intake of iron at 100 ppm. Overall, altering dietary iron intake exacerbated DSS-induced colitis; increasing the iron content of the diet also led to changes in intestinal bacteria diversity and composition after colitis was induced with DSS.
Assuntos
Anemia/tratamento farmacológico , Colite/dietoterapia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Ferro da Dieta/administração & dosagem , Ferro/metabolismo , Administração Oral , Anemia/microbiologia , Anemia/patologia , Animais , Colite/induzido quimicamente , Colite/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Camundongos , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND/AIMS: Crohn's disease (CD) and ulcerative colitis (UC) are both typified by an altered intestinal microbiota, and gene associations imply various defects in the mucosal barrier and in the innate immune response to bacteria. This review aims to assess how alterations in diet or use of modified bacteria could have therapeutic effects in CD or UC. METHODS: A MEDLINE search using the terms 'prebiotic', 'genetically modified bacteria', 'mucosal barrier in association with ulcerative colitis', 'Crohn's disease' or 'microbiota'. RESULTS: A large body of data from in vitro and animal studies shows promise for therapeutic approaches that target the microbiota. Approaches include dietary supplementation with fermentable fibres (prebiotics) and soluble fibres that block bacterial-epithelial adherence (contrabiotics), enhancement of the mucosal barrier with phosphatidylcholine, and use of genetically modified bacteria that express IL-10 or protease inhibitors. Vitamin D supplementation also shows promise, acting via enhancement of innate immunity. Clinical trials have shown benefit with enterically delivered phosphatidylcholine supplementation in UC and near-significant benefit with vitamin D supplementation in CD. CONCLUSION: Strategies that target the microbiota or the host defence against it appear to be good prospects for therapy and deserve greater investment.
Assuntos
Bactérias/metabolismo , Dieta , Doenças Inflamatórias Intestinais/dietoterapia , Doenças Inflamatórias Intestinais/microbiologia , Microbiota , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Doenças Inflamatórias Intestinais/imunologia , Microbiota/efeitos dos fármacos , Prebióticos , Vitamina D/farmacologia , Vitamina D/uso terapêuticoRESUMO
Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1-99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5-10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64-81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75-90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis.