Modification of the Gut Microbiome to Maintain Health or Treat DiseaseManipulation of the Microbiota for Treatment of IBS and IBD—Challenges and Controversies
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
References (66)
Probiotics in perspective
Gastroenterology
(2010)- et al.
Probiotics in transition
Clin Gastroenterol Hepatol
(2012) - et al.
Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era
Gastroenterology
(2009) - et al.
Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine
Cell
(2010) - et al.
Stimulation of transforming growth factor beta1 by enteric bacteria in the pathogenesis of rat intestinal fibrosis
Gastroenterology
(1998) - et al.
Functional bowel disorders
Gastroenterology
(2006) - et al.
Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome
Am J Gastroenterol
(2000) Therapies aimed at the gut microbiota and inflammation. Antibiotics, probiotics/prebiotics/synbiotics, anti-inflammatory therapies
Gastroenterol Clin North Am
(2011)The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders
Gastroenterology
(1996)- et al.
Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses
Biol Psychiatry
(2009)
A commentary on the safety of probiotics
Gastroenterol Clin North Am
An overview of fecal microbiota transplantation: techniques, indications, and outcomes
Gastrointest Endosc
Metagenomics and personalized medicine
Cell
The gut microbiota–a clinical perspective on lessons learned
Nat Rev Gastroenterol Hepatol
Alleviating cancer drug toxicity by inhibiting a bacterial enzyme
Science
The microbiota in inflammatory bowel disease: friend, bystander, and sometime-villain
Nutr Rev
The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review
Gut
Efficacy of probiotics in irritable bowel syndrome: a meta-analysis of randomized, controlled trials
Dis Colon Rectum
Meta-analysis of probiotics for the treatment of irritable bowel syndrome
World J Gastroenterol
The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review
Am J Gastroenterol
Probiotics for maintenance of remission in Crohn's disease
Cochrane Database Syst Rev
A meta-analysis on the efficacy of probiotics for maintenance of remission and prevention of clinical and endoscopic relapse in Crohn's disease
Dig Dis Sci
Meta-analysis: the effect and adverse events of Lactobacilli versus placebo in maintenance therapy for Crohn disease
Intern Med J
Interventions for prevention of post-operative recurrence of Crohn's disease
Cochrane Database Syst Rev
Meta-analysis: targeting the intestinal microbiota in prophylaxis for post-operative Crohn's disease
Aliment Pharmacol Ther
Remission induction and maintenance effect of probiotics on ulcerative colitis: a meta-analysis
World J Gastroenterol
Probiotics for maintenance of remission in ulcerative colitis
Cochrane Database Syst Rev
Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Report of a joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria
Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses
Science
The role of gastrointestinal microflora in postsurgical adhesion formation–a study in germfree rats
Eur Surg Res
Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts
Am J Physiol
A new animal model of postsurgical bowel inflammation and fibrosis: the effect of commensal microflora
Gut
Cited by (141)
Age-related diseases, therapies and gut microbiome: A new frontier for healthy aging
2022, Mechanisms of Ageing and DevelopmentAssociation Between Gastrointestinal Symptoms and Depression in a Representative Sample of Adults in the United States: Findings From National Health and Nutrition Examination Survey (2005–2016)
2022, Journal of the Academy of Consultation-Liaison Psychiatry1.38 - Gut Microbiota Dysbiosis and COVID-19: Possible Links
2022, Comprehensive Gut MicrobiotaModulation of gut microbiota: a novel approach to enhancing the effects of immune checkpoint inhibitors
2023, Therapeutic Advances in Medical Oncology
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).