The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic

Food and Agricultural Organization of the United Nations and World Health Organization. Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. World Health Organization [online] , (2001).

Food and Agricultural Organization of the United Nations and World Health Organization. Joint FAO/WHO working group report on drafting guidelines for the evaluation of probiotics in food. Food and Agricultural Organization of the United Nations [online] , (2002).

Health Canada. Accepted Claims about the Nature of Probiotic Microorganisms in Food. Health Canada [online] , (2009).

Guarner, F. et al. World Gastroenterology Organisation Global Guidelines: probiotics and prebiotics October 2011. J. Clin. Gastroenterol. 46, 468–481 (2012).

Ohr, L. M. Health benefits of probiotics and prebiotics. Institute of Food Technologists [online] , (2010).

Sanders, M. E. How do we know when something called “probiotic” is really a probiotic? A guideline for consumers and health care professionals. Functional Food Rev. 1, 3–12 (2009).

Food Safety Authority of Ireland. Probiotic Health Claims. Food Safety Authority of Ireland [online] , (2013).

Smug, L. N., Salminen, S., Sanders, M. E. & Ebner, S. Yoghurt and probiotic bacteria in dietary guidelines of the member states of the European Union. Benef. Microbes 5, 61–66 (2014).

Ministero della Salute, Commissione unica per la nutrizione e la dietetica. Guidelines on probiotics and prebiotics. Ministero della Salute [online] , (2013).

Backhed, F. et al. Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe 12, 611–622 (2012).

Ritchie, M. L. & Romanuk, T. N. A meta-analysis of probiotic efficacy for gastrointestinal diseases. PLoS ONE 7, e34938 (2012).

Bernaola Aponte, G., Bada Mancilla, C. A., Carreazo, N. Y. & Rojas Galarza, R. A. Probiotics for treating persistent diarrhoea in children. Cochrane Database of Systematic Reviews, Issue 8. Art. No.: CD007401 http://dx.doi.org/10.1002/14651858.CD007401.pub3 .

Goldenberg, J. Z. et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database of Systematic Reviews, Issue 5. Art. No.: CD006095 http://dx.doi.org/10.1002/14651858.CD006095.pub3 .

Alfaleh, K., Anabrees, J., Bassler, D. & Al-Kharfi, T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD005496 http://dx.doi.org/10.1002/14651858.CD005496.pub3 .

Allen, S. J., Martinez, E. G., Gregorio, G. V. & Dans, L. F. Probiotics for treating acute infectious diarrhoea. Cochrane Database of Systematic Reviews Issue 11. Art. No.: CD003048 http://dx.doi.org/10.1002/14651858.CD003048.pub3 .

Lomax, A. R. & Calder, P. C. Probiotics, immune function, infection and inflammation: a review of the evidence from studies conducted in humans. Curr. Pharm. Des. 15, 1428–1518 (2009).

Maidens, C., Childs, C., Przemska, A., Dayel, I. B. & Yaqoob, P. Modulation of vaccine response by concomitant probiotic administration. Br. J. Clin. Pharmacol. 75, 663–670 (2013).

Kumar, M. et al. Probiotic metabolites as epigenetic targets in the prevention of colon cancer. Nutr. Rev. 71, 23–34 (2013).

Reid, G. et al. Microbiota restoration: natural and supplemented recovery of human microbial communities. Nature Rev. Microbiol 9, 27–38 (2011).

van Baarlen, P. et al. Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4562–4569 (2011).

Heuvelin, E. et al. Mechanisms involved in alleviation of intestinal inflammation by Bifidobacterium breve soluble factors. PLoS ONE 4, e5184 (2009).

Macho Fernandez, E. et al. Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide. Gut 60, 1050–1059 (2011).

EFSA Panel on Dietetic Products, Nutrition and Allergies. Scientific Opinion on the substantiation of health claims related to live yoghurt cultures and improved lactose digestion (ID 1143, 2976) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal 8, 1763 (2010).

Tong, X., Dong, J. Y., Wu, Z. W., Li, W. & Qin, L. Q. Dairy consumption and risk of type 2 diabetes mellitus: a meta-analysis of cohort studies. Eur. J. Clin. Nutr. 65, 1027–1031 (2011).

Struijk, E. A. et al. Dairy product intake in relation to glucose regulation indices and risk of type 2 diabetes. Nutr. Metab. Cardiovasc. Dis. 23, 822–828 (2013).

Sluijs, I. et al. The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct Study. Am. J. Clin. Nutr. 96, 382–390 (2012).

Mozaffarian, D., Hao, T., Rimm, E. B., Willett, W. C. & Hu, F. B. Changes in diet and lifestyle and long-term weight gain in women and men. N. Engl. J. Med. 364, 2392–2404 (2011).

Soedamah-Muthu, S. S., Masset, G., Verberne, L., Geleijnse, J. M. & Brunner, E. J. Consumption of dairy products and associations with incident diabetes, CHD and mortality in the Whitehall II study. Br. J. Nutr. 109, 718–726 (2013).

Wang, H., Livingston, K. A., Fox, C. S., Meigs, J. B. & Jacques, P. F. Yogurt consumption is associated with better diet quality and metabolic profile in American men and women. Nutr. Res. 33, 18–26 (2013).

Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).

Lepage, P. et al. Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 141, 227–236 (2011).

Manichanh, C., Borruel, N., Casellas, F. & Guarner, F. The gut microbiota in IBD. Nat. Rev. Gastroenterol. Hepatol. 9, 599–608 (2012).

Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60 (2012).

Le Chatelier, E. et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546 (2013).

Jeffery, I. B. et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 61, 997–1006 (2012).

Rajilic-Stojanovic, M. et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 141, 1792–1801 (2011).

Hviid, A., Svanstrom, H. & Frisch, M. Antibiotic use and inflammatory bowel diseases in childhood. Gut 60, 49–54 (2011).

Trasande, L. et al. Infant antibiotic exposures and early-life body mass. Int. J. Obes. (Lond.) 37, 16–23 (2013).

Guarner, F. et al. Mechanisms of disease: the hygiene hypothesis revisited. Nat. Clin. Pract. Gastroenterol. Hepatol. 3, 275–284 (2006).

Blaser, M. J. & Falkow, S. What are the consequences of the disappearing human microbiota? Nat. Rev. Microbiol. 7, 887–894 (2009).

Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 16731–16736 (2008).

Atarashi, K. et al. Treg induction by a rationally selected mixture of clostridia strains from the human microbiota. Nature 500, 232–236 (2013).

Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl Acad. Sci. USA 110, 9066–9071 (2013).

Joyce, S. A. & Gahan, C. G. The gut microbiota and the metabolic health of the host. Curr. Opin. Gastroenterol. 30, 120–127 (2014).

Miquel, S. et al. Faecalibacterium prausnitzii and human intestinal health. Curr. Opin. Microbiol. 16, 255–261 (2013).

Louis, P., Scott, K. P., Duncan, S. H. & Flint, H. J. Understanding the effects of diet on bacterial metabolism in the large intestine. J. Appl. Microbiol. 102, 1197–1208 (2007).

Vrieze, A. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913–916 (2012).

Smits, L. P., Bouter, K. E., de Vos, W. M., Borody, T. J. & Nieuwdorp, M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology 145, 946–953 (2013).

van Nood, E. et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368, 407–415 (2013).

Allen-Vercoe, E. et al. A Canadian Working Group report on fecal microbial therapy: microbial ecosystems therapeutics. Can. J. Gastroenterol. 26, 457–462 (2012).

Caporaso, J. G. et al. Moving pictures of the human microbiome. Genome Biol. 12, R50 (2011).

US Department of Health & Human Services. Guidance for industry: enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat Clostridium difficile infection not responsive to standard therapies. US Food and Drug Administration [online] , (2013).

Petrof, E. O. et al. Stool substitute transplant therapy for the eradication of C. difficile infection: 'RePOOPulating the gut'. Microbiome 1, 3 (2013).

Petrof, E. O., Claud, E. C., Gloor, G. B. & Allen-Vercoe, E. Microbial ecosystems therapeutics: a new paradigm in medicine? Benef. Microbes 4, 53–65 (2013).

Schunemann, H., Hill, S., Guyatt, G., Akl, E. A. & Ahmed, F. The GRADE approach and Bradford §Hill's criteria for causation. J. Epidemiol. Community Health 65, 392–395 (2011).

Gordis, L. Epidemiology (W. B. Saunder Company, 2000).

European Food Safety Authority. Scientific opinion on the substantiation of health claims related to vitamin C and reduction of tiredness and fatigue (ID 139, 2622), contribution to normal psychological functions (ID 140), regeneration of the reduced form of vitamin E (ID 202), contribution to normal energy-yielding metabolism (ID 2334, 3196), maintenance of the normal function of the immune system (ID 4321) and protection of DNA, proteins and lipids from oxidative damage (ID 3331) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal 8, 1815 (2010).

Hemila, H. Vitamin C and the common cold. Br. J. Nutr. 67, 3–16 (1992).

Hemila, H. Vitamin C and common cold incidence: a review of studies with subjects under heavy physical stress. Int. J. Sports Med. 17, 379–383 (1996).

Hemila, H. & Chalker, E. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD000980 http:/dx.doi.org/10.1002/14651858.CD000980.pub4 .

Douglas, R. M., Hemila, H., Chalker, E. & Treacy, B. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD000980 http://dx.doi.org/10.1002/14651858.CD000980.pub3 .

Winzenberg, T. M., Powell, S., Shaw, K. A. & Jones, G. Vitamin D supplementation for improving bone mineral density in children. Cochrane Database of Systematic Reviews, Issue 10. Art No.: CD006944 http://dx.doi.org/10.1002/14651858.CD006944.pub2 .

Hao, Q., Lu, Z., Dong, B. R., Huang, C. Q. & Wu, T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database of Systematic Reviews, Issue 9. Art. No.: CD006895 http://dx.doi.org/10.1002/14651858.CD006895.pub2 .

Johnston, B. C. et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann. Intern. Med. 157, 878–888 (2012).

Hempel, S. et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA 307, 1959–1969 (2012).

Hoveyda, N. et al. A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome. BMC Gastroenterol. 9, 15 (2009).

Reid, G. Microbiology: Categorize probiotics to speed research. Nature 485, 446 (2012).

Sanders, M. E. et al.Probiotics and prebiotics: prospects for public health and nutritional recommendations. Ann. N.Y. Acad. Sci. 1309, 19–29 (2014).

Hill, C. & Sanders, M. E. Rethinking “probiotics”. Gut Microbes 4, 269–270 (2013).

Hoffmann, D. E. et al. Science and regulation. Probiotics: finding the right regulatory balance. Science 342, 314–315 (2013).

US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research & Center for Food Safety and Applied Nutrition. Guidance for clinical investigators, sponsors, and IRBs. Investigational new drug applications (INDs)—determining whether human research studies can be conducted without an IND. US Food and Drug Administration [online] , (2013).

Hungin, A. P. et al. Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice—an evidence-based international guide. Aliment. Pharmacol. Ther. 38, 864–886 (2013).

Bertazzoni, E., Donelli, G., Midtvedt, T., Nicoli, J. & Sanz, Y. Probiotics and clinical effects: is the number what counts? J. Chemother. 25, 193–212 (2013).

de Vrese, M. et al. Probiotics—compensation for lactase insufficiency. Am. J. Clin. Nutr. 73, 421S–429S (2001).

Guarner, F. et al. Should yoghurt cultures be considered probiotic? Br. J. Nutr. 93, 783–786 (2005).

European Food Safety Authority. Introduction of a Qualified Presumption of Safety (QPS) approach for assessment of selected microorganisms referred to EFSA—Opinion of the Scientific Committee [online] , (2007).

US Department of Health & Human Services. Generally Recognized as Safe (GRAS). US Food and Drug Administration [online] , (2013).

Higgins, J. & Green, S. Cochrane Handbook for Systematic Reviews of Interventions (John Wiley & Sons Ltd, 2008).

International Life Sciences Institute—Europe. PASSCLAIM. A European Commission Concerted Action Programme. International Life Sciences Institute [online] , (2005).

GRADE Working Group. Grading the quality of evidence and the strength of recommendations. GRADE [online] , (2013).

van Loveren, H., Sanz, Y. & Salminen, S. Health claims in Europe: probiotics and prebiotics as case examples. Annu. Rev. Food Sci. Technol. 3, 247–261 (2012).