Characterisation and therapeutic manipulation of the gut microbiome in inflammatory bowel disease.

Inflammatory bowel diseases are thought to develop as a result of dysregulation of the relationship that exists between the gut microbiota, host genetics and the immune system. The advent of culture-independent techniques has revolutionised the ability to characterise the role of the gut microbiota in health and disease based on the microbiota's genetic make-up. Inflammatory bowel diseases are characterised by dysbiosis which is an imbalance between pro- and anti-inflammatory bacteria and a reduction in bacterial diversity. Emerging data suggest that it is not only the presence of the gut microbiota but the functional activity of the microbiota that appears to play an important role in health and disease. Current strategies to manipulate therapeutically the gut microbiota using dietary modification, prebiotics, probiotics, antibiotics and faecal microbiota transplantation aim to restore the balance to a state of normobiosis. However, the ability of such strategies to correct dysbiosis and thereby achieve therapeutic benefit is yet to be fully characterised.

Schulberg J ，De Cruz P 《-》

Therapeutic modulation of gut microbiota in inflammatory bowel disease: More questions to be answered.

Patients with inflammatory bowel disease (IBD) exhibit impaired control of the microbiome in the gut, and 'dysbiosis' is commonly observed. Western diet is a risk factor for the development of IBD, but it may have different effects on gut microbiota between IBD and non-IBD individuals. Exclusive enteral nutrition (EEN) can induce remission in pediatric Crohn's disease with a decrease in gut microbial diversity. Although there are some theoretical benefits, actual treatment effects of prebiotics and probiotics in IBD vary. High-quality studies have shown that VSL#3 (a high-potency probiotic medical food containing eight different strains) exhibits benefits in treating ulcerative colitis, and gut microbial diversity is reduced after treated with VSL#3 in animal models. The effect of fecal microbiome transplantation on IBD is controversial. Increasing microbial diversity compared with impaired handling of bacteria presents a dilemma. Antibiotics are the strongest factors in the reduction of microbiome ecological diversity. Some antibiotics may help to induce remission of the disease. Microbiome alteration has been suggested to be an intrinsic property of IBD and a potential predictor in diagnosis and prognosis. However, the effects of therapeutic modulations are variable; thus, more questions remain to be answered.

Qiao YQ ，Cai CW ，Ran ZH 《-》

The involvement of gut microbiota in inflammatory bowel disease pathogenesis: potential for therapy.

Over the past recent years, a great number of studies have been directed toward the evaluation of the human host-gut microbiota interaction, with the goal to progress the understanding of the etiology of several complex diseases. Alterations in the intestinal microbiota associated with inflammatory bowel disease are well supported by literature data and have been widely accepted by the research community. The concomitant implementation of high-throughput sequencing techniques to analyze and characterize the composition of the intestinal microbiota has reinforced the view that inflammatory bowel disease results from altered interactions between gut microbes and the mucosal immune system and has raised the possibility that some form of modulation of the intestinal microbiota may constitute a potential therapeutic basis for the disease. The aim of this review is to describe the changes of gut microbiota in inflammatory bowel disease, focusing the attention on its involvement in the pathogenesis of the disease, and to review and discuss the therapeutic potential to modify the intestinal microbial population with antibiotics, probiotics, prebiotics, synbiotics and fecal microbiota transplantation.

Cammarota G ，Ianiro G ，Cianci R ，Bibbò S ，Gasbarrini A ，Currò D ... -  《-》

Gut microbiota in the pathogenesis of inflammatory bowel disease.

Nishida A ，Inoue R ，Inatomi O ，Bamba S ，Naito Y ，Andoh A ... -  《-》

Antibiotics, probiotics and prebiotics in IBD.

The dysbiosis theory of inflammatory bowel disease (IBD) posits that there is an alteration in the gut microbiome as an important underpinning of disease etiology. It stands to reason then, that administering agents that could impact on the balance of microbes on the gut could be impactful on the course of IBD. Herein is a review of the controlled trials undertaken to assess the use of antibiotics that would kill or suppress potentially injurious microbes, probiotics that would overpopulate the gut with potentially beneficial microbes or prebiotics that provide a metabolic substrate that enhances the growth of potentially beneficial microbes. With regard to antibiotics, the best data are for the use of nitroimadoles postoperatively in Crohn's disease (CD) to prevent disease recurrence. Otherwise, the data are limited with the regard to any lasting benefit of antibiotics sustaining remission in either CD or ulcerative colitis (UC). A recent meta-analysis concluded that antibiotics are superior to placebo at inducing remission in CD or UC, although the meta-analysis grouped a variety of antibiotics with different spectra of activity. Despite the absence of robust clinical trial data, antibiotics are widely used to treat perineal fistulizing CD and acute and chronic pouchitis. Probiotics have not been shown to have a beneficial role in CD. However, Escherichia coli Nissle 1917 has comparable effects to low doses of mesalamine in maintaining remission in UC. VSL#3, a combination of 8 microbes, has been shown to have an effect in inducing remission in UC and preventing pouchitis. Prebiotics have yet to be shown to have an effect in any form of IBD, but to date controlled trials have been small. The use of antibiotics should be balanced against the risks they pose. Even probiotics may pose some risk and should not be assumed to be innocuous especially when ingested by persons with a compromised epithelial barrier. Prebiotics may not be harmful but may cause gastrointestinal side effects. Finally, the timing of ingestion of antibiotics and other dietary factors that may function as prebiotics, especially in early childhood, may be critical in shaping the gut microbiome and ultimately predisposing to or preventing IBD. Finding ways to impact on the gut microbiome to alter the course of IBD makes good sense, but should be undertaken in the setting of rigorously performed controlled trials to ensure that the interventions are truly effective and well tolerated.

Bernstein CN 《-》