Gastroenterology

Gastroenterology

Volume 146, Issue 6, May 2014, Pages 1554-1563
Gastroenterology

Modification of the Gut Microbiome to Maintain Health or Treat Disease
Manipulation of the Microbiota for Treatment of IBS and IBD—Challenges and Controversies

https://doi.org/10.1053/j.gastro.2014.01.050Get rights and content

There is compelling rationale for manipulating the microbiota to treat inflammatory bowel diseases (IBDs). Although studies of animal models of intestinal inflammation produced promising results, trials in humans have been disappointing. In contrast to IBD, the role of the microbiota in the development of irritable bowel syndrome (IBS) only recently has been considered, but early stage results have been encouraging. As pharmaceutical companies develop fewer truly novel agents for treatment of these disorders, consumers seek safer, long-term strategies to deal with chronic symptoms. We assess the rationale for modulating the microbiota for treatment of IBD and IBS, and discuss whether current concepts are simplistic and overstated or simply under-researched. Are claims exaggerated and expectations unrealistic? Difficulties with microbiota terminology and technologies, as well as differences among patients and the heterogeneity of these diseases, pose additional challenges in developing microbiota-based therapies for IBD and IBS.

Section snippets

Tyranny of Terminology

Not only politicians, but scientists and clinical researchers would do well to mind George Orwell's18 refrain “…the slovenliness of our language makes it easier…to have foolish thoughts.” Inaccurate thinking can arise when clinicians become captive to errors in nomenclature and imprecise terminology. Neologisms should be used with caution; they often are unnecessary or imply an understanding where none exists. For example, the term dysbiosis is unhelpful if used to merely describe a change in

Manipulation of the Microbiota to Treat IBD and IBS

The intestinal microbiota is involved in the pathogenesis of Crohn's disease and ulcerative colitis, but it is unclear whether tissue damage results from an abnormal immune response to a normal microbiota or from a normal immune response against an abnormal microbiota. Animal models provide evidence for each possibility, and show that immune deficits can change the microbiota toward one with a colitogenic capacity.5

Animal models also illustrate the complexity and heterogeneity of microbes that

IBD

Theoretically, there are several opportunities for therapeutic manipulation of the microbiota to reduce clinical manifestations at different stages of IBD (Figure 2). However, the opportunity to prevent or reverse pathologic immune responses before diseases such as IBD develop likely is limited—confined to a period of life when microbial colonization occurs and mucosal barrier function, the blood-brain barrier, and the immune system are developing.

Several lines of evidence indicate that

Disparities in Findings From Animal and Human Studies

Animal models have helped us explore the interactions among genetic and environmental factors that increase susceptibility to IBD, as well as the bidirectional nature of host-microbe communications and the effects of the microbiota on host metabolism. Although animal models are important for studying inflammation, there are disparities in the results of modifying the microbiota in mice vs humans. These disparities have contributed to unrealistic expectations for potential effects in humans. The

Impediments to Linking Science With the Consumer

Health food stores, pharmacies, and supermarkets display an increasing range of so-called probiotics, in diverse formulations. However, few of these are true probiotics; most have not undergone any type of quality control, provided evidence for their health benefits, or even been tested in humans. Until the contents and health claims of these products are regulated, consumers will have difficulties distinguishing those that are helpful from those of no proven value.

Reassuringly, reputable major

Prospects and Priorities for the Next Generation of Ecotherapies

Predicting the future for a rapidly moving field is foolhardy but certain requirements and gaps in knowledge can be identified. First, better biomarkers are needed, not only for predicting disease onset or relapse, but also for disease risk. It can be anticipated that new microbial biomarkers for IBD risk will emerge to complement host genetic risk factors. Furthermore, microbial biomarkers might be identified that define subsets of IBD and IBS. The clinical heterogeneity of IBD predicts

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    Conflicts of interest The authors disclose the following: Fergus Shanahan and Eamonn Quigley are shareholders in a university campus company, Alimentary Health, Ltd, and have consulted and/or received research grants from Procter and Gamble Co and GlaxoSmithKline.

    Funding Supported in part by grants from the Science Foundation Ireland in the form of a center grant (Alimentary Pharmabiotic Centre; grants SFI/12/RC/2273 and 12/RC/2273).

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