Invited Editorials bacterial presentation to macrophages and offers a potential mechanistic role. Notwithstanding the complexity of assessing breath VOCs due to the high humidity factor and respiratory variables (e.g. flow rate, tidal volume capture), breathomics offers exciting potential for routine diagnostics in IBD.6 The challenge remains to develop technology adapted for point of care testing, which will bring a new scent to IBD.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Patel N, Alkhouri N, Eng K, et al. Metabolomic analysis of breath volatile organic compounds reveals unique breathprints in
Editorial: gut microbiota and chemotherapy- or radiation-induced gastrointestinal mucositis M. R. Ferreira*,† & H. J. N. Andreyev† *Institute of Cancer Research, Instituto Gulbenkian Ci^encia, London, UK. † Royal Marsden NHS Foundation Trust, London, UK. E-mail: [email protected] doi:10.1111/apt.12905
Chemotherapy-induced diarrhoea forces hospital admission in up to 1000 patients per month in the UK alone; clinical trials consistently show that up to 5% of patients treated with chemotherapy die, at least partly, as a result of GI toxicity from that chemotherapy. In addition, more patients develop chronic life-detracting gastrointestinal morbidity after radiotherapy per year than are diagnosed with Crohn’s disease. It is pleasing to read that gastroenterologists are starting to consider these issues after years of almost completely ignoring this epidemic of GI morbidity.1 Research in this patient group will be very fruitful. Cancer therapy-induced GI morbidity is a magnificent model of human gastrointestinal disease – especially IBD. Most importantly, it has a known ‘start date’ so that tissue and patients can be studied before, during and after the ‘disease’ strikes.2 The recent interest in intestinal flora is partly driven by technological advances, particularly metagenomic sequencing and marker gene-based phylotyping. From this, we understand that our microbiota is far more Aliment Pharmacol Ther 2014; 40: 727-734 ª 2014 John Wiley & Sons Ltd
2. 3.
4.
5.
6.
children with inflammatory bowel disease: a pilot study. Aliment Pharmacol Ther 2014; 40: 498–507. Cao W, Duan Y. Current status of methods and techniques for breath analysis. Crit Rev Anal Chem 2007; 37: 3–13. Kokoszka J, Nelson RL, Swedler WI, et al. Determination of inflammatory bowel disease activity by breath pentane analysis. Dis Colon Rectum 1993; 36: 597–601. Pelli MA, Trovarellu G, Capodicasa E, et al. Breath alkanes determination in ulcerative colitis and Crohn’s disease. Dis Colon Rectum 1999; 42: 71–6. Rampersad G, Suck G, Sakac D, et al. Chemical compounds that target thiol-disulphide groups on mononuclear phagocytes inhibit immune mediated phagocytosis of red blood cells. Transfusion 2005; 45: 384–93. Arasaradnam RP, Covington JA, Harmston C, Nwokolo CU. Review article: next generation diagnostic modalities in gastroenterology – gas phase volatile compound biomarker detection. Alimentary Pharmacology & Therapeutics 2014; 39: 780–789.
diverse than previously thought3, 4 and dysbiosis is clearly associated with human diseases.5 The central, still unanswered question is whether pre-existing dysbiosis provokes gastrointestinal disease, is an epiphenomenon, or develops because of the disease and then drives the disease processes. Similar diseases demonstrate widely different microbial patterns6 as is very clearly shown in this review, so the hypothesis that a dysbiotic environment initiates bowel disease seems increasingly untenable.1 It seems much more likely that the absolute composition or relative changes in the microbiota are irrelevant, and instead, what is important is how the microbiota behaves, and how its functions change.7 Studies in those undergoing cancer therapy will lead to a new era in the treatment and prevention of the currently dreadful GI toxicity suffered by so many patients, and what we learn will almost certainly bring important insights to many other GI disorders.
ACKNOWLEDGEMENTS Declaration of personal interests: None. Declaration of funding interests: M.R.F. is supported by grants from the Fundacao para a Ciencia e Tecnologia, Fundacao Calouste Gulbenkian and the Champalimaud Foundation. We acknowledge support from the National Institute for Health Research, Royal Marsden Biomedical Research Centre.
REFERENCES 1. Touchefeu Y, Montassier E, Nieman K, et al. Systematic review: the role of the gut microbiota in chemotherapy- or radiation733
Invited Editorials induced gastrointestinal mucositis – current evidence, potential clinical applications. Aliment Pharmacol Ther 2014; 40: 409–21. 2. Bowen R, Miller P, Shanahan MT, Packey CD, Sartor RB. Radiation exposure induces dysbioses throughout the small intestinal, colonic lumen, mucosa that resemble those seen in human inflammatory bowel diseases. Inflamm Bowel Dis 2011; 17 (Suppl. 2): S86. 3. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science 2005; 308: 1635–8. 4. Human Microbiome Project Consortium. Structure, function, diversity of the healthy human microbiome. Nature 2012; 486: 207–14.
734
5. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009; 361: 2066–78. 6. Andoh A, Imaeda H, Aomatsu T, et al. Comparison of the fecal microbiota profiles between ulcerative colitis, Crohn’s disease using terminal restriction fragment length polymorphism analysis. J Gastroenterol 2011; 46: 479–86. 7. Holmes E, Li JV, Marchesi JR, Nicholson JK. Gut microbiota composition, activity in relation to host metabolic phenotype, disease risk. Cell Metab 2012; 16: 559–64.
Aliment Pharmacol Ther 2014; 40: 727-734 ª 2014 John Wiley & Sons Ltd
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Patel N, Alkhouri N, Eng K, et al. Metabolomic analysis of breath volatile organic compounds reveals unique breathprints in
Editorial: gut microbiota and chemotherapy- or radiation-induced gastrointestinal mucositis M. R. Ferreira*,† & H. J. N. Andreyev† *Institute of Cancer Research, Instituto Gulbenkian Ci^encia, London, UK. † Royal Marsden NHS Foundation Trust, London, UK. E-mail: [email protected] doi:10.1111/apt.12905
Chemotherapy-induced diarrhoea forces hospital admission in up to 1000 patients per month in the UK alone; clinical trials consistently show that up to 5% of patients treated with chemotherapy die, at least partly, as a result of GI toxicity from that chemotherapy. In addition, more patients develop chronic life-detracting gastrointestinal morbidity after radiotherapy per year than are diagnosed with Crohn’s disease. It is pleasing to read that gastroenterologists are starting to consider these issues after years of almost completely ignoring this epidemic of GI morbidity.1 Research in this patient group will be very fruitful. Cancer therapy-induced GI morbidity is a magnificent model of human gastrointestinal disease – especially IBD. Most importantly, it has a known ‘start date’ so that tissue and patients can be studied before, during and after the ‘disease’ strikes.2 The recent interest in intestinal flora is partly driven by technological advances, particularly metagenomic sequencing and marker gene-based phylotyping. From this, we understand that our microbiota is far more Aliment Pharmacol Ther 2014; 40: 727-734 ª 2014 John Wiley & Sons Ltd
2. 3.
4.
5.
6.
children with inflammatory bowel disease: a pilot study. Aliment Pharmacol Ther 2014; 40: 498–507. Cao W, Duan Y. Current status of methods and techniques for breath analysis. Crit Rev Anal Chem 2007; 37: 3–13. Kokoszka J, Nelson RL, Swedler WI, et al. Determination of inflammatory bowel disease activity by breath pentane analysis. Dis Colon Rectum 1993; 36: 597–601. Pelli MA, Trovarellu G, Capodicasa E, et al. Breath alkanes determination in ulcerative colitis and Crohn’s disease. Dis Colon Rectum 1999; 42: 71–6. Rampersad G, Suck G, Sakac D, et al. Chemical compounds that target thiol-disulphide groups on mononuclear phagocytes inhibit immune mediated phagocytosis of red blood cells. Transfusion 2005; 45: 384–93. Arasaradnam RP, Covington JA, Harmston C, Nwokolo CU. Review article: next generation diagnostic modalities in gastroenterology – gas phase volatile compound biomarker detection. Alimentary Pharmacology & Therapeutics 2014; 39: 780–789.
diverse than previously thought3, 4 and dysbiosis is clearly associated with human diseases.5 The central, still unanswered question is whether pre-existing dysbiosis provokes gastrointestinal disease, is an epiphenomenon, or develops because of the disease and then drives the disease processes. Similar diseases demonstrate widely different microbial patterns6 as is very clearly shown in this review, so the hypothesis that a dysbiotic environment initiates bowel disease seems increasingly untenable.1 It seems much more likely that the absolute composition or relative changes in the microbiota are irrelevant, and instead, what is important is how the microbiota behaves, and how its functions change.7 Studies in those undergoing cancer therapy will lead to a new era in the treatment and prevention of the currently dreadful GI toxicity suffered by so many patients, and what we learn will almost certainly bring important insights to many other GI disorders.
ACKNOWLEDGEMENTS Declaration of personal interests: None. Declaration of funding interests: M.R.F. is supported by grants from the Fundacao para a Ciencia e Tecnologia, Fundacao Calouste Gulbenkian and the Champalimaud Foundation. We acknowledge support from the National Institute for Health Research, Royal Marsden Biomedical Research Centre.
REFERENCES 1. Touchefeu Y, Montassier E, Nieman K, et al. Systematic review: the role of the gut microbiota in chemotherapy- or radiation733
Invited Editorials induced gastrointestinal mucositis – current evidence, potential clinical applications. Aliment Pharmacol Ther 2014; 40: 409–21. 2. Bowen R, Miller P, Shanahan MT, Packey CD, Sartor RB. Radiation exposure induces dysbioses throughout the small intestinal, colonic lumen, mucosa that resemble those seen in human inflammatory bowel diseases. Inflamm Bowel Dis 2011; 17 (Suppl. 2): S86. 3. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science 2005; 308: 1635–8. 4. Human Microbiome Project Consortium. Structure, function, diversity of the healthy human microbiome. Nature 2012; 486: 207–14.
734
5. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009; 361: 2066–78. 6. Andoh A, Imaeda H, Aomatsu T, et al. Comparison of the fecal microbiota profiles between ulcerative colitis, Crohn’s disease using terminal restriction fragment length polymorphism analysis. J Gastroenterol 2011; 46: 479–86. 7. Holmes E, Li JV, Marchesi JR, Nicholson JK. Gut microbiota composition, activity in relation to host metabolic phenotype, disease risk. Cell Metab 2012; 16: 559–64.
Aliment Pharmacol Ther 2014; 40: 727-734 ª 2014 John Wiley & Sons Ltd
