SummaryBackgroundApplication of modern rapid DNA sequencing technology has transformed our understanding of the gut microbiota. Diet, in particular plant‐based fibre, appears critical in influencing the composition and metabolic activity of the microbiome, determining levels of short‐chain fatty acids (SCFAs) important for intestinal health.AimTo assess current epidemiological, experimental and clinical evidence of how long‐term and short‐term alterations in dietary fibre intake impact on the microbiome and metabolome.MethodsA Medline search including items ‘intestinal microbiota’, ‘nutrition’, ‘diet’, ‘dietary fibre’, ‘SCFAs’ and ‘prebiotic effect’ was performed.ResultsStudies found evidence of fibre‐influenced differences in the microbiome and metabolome as a consequence of habitual diet, and of long‐term or short‐term intervention (in both animals and humans).ConclusionsAgrarian diets high in fruit/legume fibre are associated with greater microbial diversity and a predominance of Prevotella over Bacteroides. ‘Western’‐style diets, high in fat/sugar, low in fibre, decrease beneficial Firmicutes that metabolise dietary plant‐derived polysaccharides to SCFAs and increase mucosa‐associated Proteobacteria (including enteric pathogens). Short‐term diets can also have major effects, particularly those exclusively animal‐based, and those high‐protein, low‐fermentable carbohydrate/fibre ‘weight‐loss’ diets, increasing the abundance of Bacteroides and lowering Firmicutes, with long‐term adherence to such diets likely increasing risk of colonic disease. Interventions to prevent intestinal inflammation may be achieved with fermentable prebiotic fibres that enhance beneficial Bifidobacteria or with soluble fibres that block bacterial–epithelial adherence (contrabiotics). These mechanisms may explain many of the differences in microbiota associated with long‐term ingestion of a diet rich in fruit and vegetable fibre.

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.

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.

angiogenic cascade, although the exact mechanism remains elusive. Previous research we have undertaken has associated elevated serum angiopoietin-2 (Ang-2) levels with angiodysplasia. Ang-1 and Ang-2 are ligands of the endothelial receptor tyrosine kinase Tie-2. Ang-1 regulates endothelial cell survival and blood vessel maturation and plays a key role in maintaining vascular integrity. Ang-2 is a functional antagonist of Ang-1. Inflammation and angiogenesis are associated with several pathological disorders and previous data suggests a TNF-a dependent dual functional roles of Tie2 in inflammatory angiogenesis Methods Following informed consent, serum samples were collected from patients with a definite diagnosis of sporadic small bowel angiodysplasia (P2) on capsule endoscopy, and from healthy controls in which GI bleeding had been out-ruled by a negative faecal immunochemical test. Serum levels of Ang-1, Ang-2 and TNF-a were measured using commercially available ELISA kits. All results were expressed as a mean and compared between patients and controls, and the mean of the ratio of ang2/ang1 levels for each group was calculated. Results A total of 80 samples were analysed for each factor, including 40 patients (48% male, average age 71 years) and 40 controls (43% male, average age 70 years). As expected and in keeping with our previous work levels of Ang-2 were significantly higher in patients (mean 4600 pg/ml) than in controls (mean 2973 pg/ml) p < 0.001. In addition levels of Ang-1 were significantly lower in the patient group (mean 13071 pg/ml) vs. controls (mean 21169 pg/ml) p < 0.004 (Table 1). We also found that levels of TNF-a were significantly lower in the patient group (mean 6.7 pg/ml) vs. controls (mean 12.2 pg/ml) p < 0.003. The mean of the ratio of Ang2/Ang1 levels was found to be significantly higher in patients (1.05) vs. controls (0.29) p < 0.05. Conclusion Ours is the first study to have identified a link between angiopoietin 1 and 2 ratios and gastrointestinal angiodysplasia. The TNF-a findings are also novel and would strongly suggest a role for inflammatory mediated angiogenesis in this condition.

Clostridioides difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea. Adhesion of this Gram-positive pathogen to the intestinal epithelium is a crucial step in CDI, with recurrence and relapse of disease dependent on epithelial interaction of its endospores. Close proximity, or adhesion of, hypervirulent strains to the intestinal mucosa are also likely to be necessary for the release of C. difficile toxins, which when internalized, result in intestinal epithelial cell rounding, damage, inflammation, loss of barrier function and diarrhoea. Interrupting these C. difficile-epithelium interactions could therefore represent a promising therapeutic strategy to prevent and treat CDI. Intake of dietary fibre is widely recognised as being beneficial for intestinal health, and we have previously shown that soluble non-starch polysaccharides (NSP) from plantain banana (Musa spp.), can block epithelial adhesion and invasion of a number of gut pathogens, such as E. coli and Salmonellae. Here, we assessed the action of plantain NSP, and a range of alternative soluble plant fibres, for inhibitory action on epithelial interactions of C. difficile clinical isolates, purified endospore preparations and toxins. We found that plantain NSP possessed ability to disrupt epithelial adhesion of C. difficile vegetative cells and spores, with inhibitory activity against C. difficile found within the acidic (pectin-rich) polysaccharide component, through interaction with the intestinal epithelium. Similar activity was found with NSP purified from broccoli and leek, although seen to be less potent than NSP from plantain. Whilst plantain NSP could not block the interaction and intracellular action of purified C. difficile toxins, it significantly diminished the epithelial impact of C. difficile, reducing both bacteria and toxin induced inflammation, activation of caspase 3/7 and cytotoxicity in human intestinal cell-line and murine intestinal organoid cultures. Dietary supplementation with soluble NSP from plantain may therefore confer a protective effect in CDI patients by preventing adhesion of C. difficile to the mucosa, i.e. a “contrabiotic” effect, and diminishing its epithelial impact. This suggests that plantain soluble dietary fibre may be a therapeutically effective nutritional product for use in the prevention or treatment of CDI and antibiotic-associated diarrhoea.

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