There is an almost insatiable need for information about the human microbiota. Reports about new findings on the role of our, mainly intestinal, microbes in health and disease are published in the popular press on an almost weekly basis.
Obviously, diet has a major influence on the composition and activity of the intestinal microbiota; but there are more direct ways to influence the microbiota with probiotics and prebiotics. Here, we will discuss the benefits of probiotics and the requirements for probiotics.
What is a probiotic and what isn’t?
Probiotics are live micro-organisms that, when consumed in adequate amounts, provide a health benefit to the host. Probiotics can thus be any microbe (as long as they are not pathogens), the most commonly commercially available probiotics are members of the genera Lactobacillus and Bifidobacterium, although also e.g. Saccharomyces and Bacillus probiotics are available and documented. To qualify as a probiotic, a microbe needs to fulfil a number of key criteria. These criteria have recently been summarised and clarified by the International Probiotic Association (IPA).
By definition, probiotics should have a health benefit. For those jurisdictions where claims are allowed, the manufacturer is expected to be able to document the claim, and document that the dose in the product is at least the same as the dose tested. Furthermore, probiotics should have their taxonomy identified to genus and species level, and be identifiable at the strain level. The probiotic strain should be characterised in the sense that it can be expected to survive gastro-intestinal transit, and has a history of safe use or otherwise leaves no doubt about its safety. Furthermore, there are quality requirements as stipulated in the IPA-CRN Best practices guidelines; manufacturers should mention the appropriate taxonomy on the package including strain identification (e.g. Lactobacillus acidophilus ABC). Packaging should mention the minimum number of viable microbes at the end of shelf life. If a product contains multiple strains, at least the total number at end of shelf-life should be mentioned; if the product is a proprietary combination, the counts for each strain should be reported. It is recommended that the dose be at least 109 live microbes (colony forming units, CFU).
Various health benefits have been described for probiotics and although some health benefits appear to be fairly common among probiotics, others have been shown to be very specific. Thus, no probiotic can be expected to provide all suggested health benefits; different probiotic strains may have diverse benefits.
Finally, some products are marketed as such, but do not qualify as probiotics. Examples of such products are household cleaning agents, drain cleaners and cosmetic products which contain probiotic metabolites, non-live or fragmented probiotic cells.
Health benefits of probiotics
The suggested list of health benefits of probiotics is long; Table 1. gives a brief overview. Several studies support the benefit of probiotic applications (strain specific or combinations). However, there are many health benefits for which there is not yet sufficient data available. There is evidence for a potential benefit, but further studies are required. Finally, there are health benefits for which there is, at best, emerging evidence.
Reduced risk for antibiotic associated diarrhoea (AAD)
Antibiotics are used and developed to kill pathogenic bacteria; but as a side effect, the endogenous microbiota in the intestine may also be disturbed which may result in diarrhoea. The diarrhoea may lead to secondary infections, prolong the required care and increase health care costs. Probiotics have been shown to reduce the risk for AAD by 50 percent and Clostridium difficile associated diarrhoea by more than 60 percent; they may also reduce the duration and severity of the diarrhoea. This is one of the best documented health benefits of probiotics and numerous studies and strains have been documented to provide benefits in conjunction with antibiotic use. This has also been associated with substantial net savings. Furthermore, the importance of taking probiotics immediately after the start of the antibiotic treatment is evident. It can be hypothesised that probiotics support the intestine’s microbiota in managing the onslaught of the antibiotic, rather than replenishing killed microbes.
Reduced risk for necrotising enterocolitis
Necrotising enterocolitis (NEC) is a very severe condition that affects extremely low birth weight infants. There is currently no cure for NEC; fortunately, the condition is quite rare. Interestingly, probiotics have been shown to effectively reduce the risk for NEC. However, as the disease is rare, studies usually have a limited number of patients. Nevertheless, the results are very consistent; some authors have even suggested it might be unethical to not routinely use probiotics in children at-risk. The challenge is that it appears difficult to decide what strain (combination) and dose to recommend. Most recent analyses suggest that probiotic combinations would be most efficacious; with an odds ratio of 0.58. Probiotics are thought to support the establishment of a beneficial or at least non-pathogenic microbiota and may also support the development of the immune system in premature infants.
Reduced risk for respiratory tract infections
Respiratory tract infections (RTI) are considered to be one of the most common diseases; people will suffer from one or more bouts of cold or flu in their lifetime. In most cases, these infections are benign and resolve on their own. But in the rare case, they may lead to more serious secondary infections. Consumption of probiotics during the winter months has been reported to shorten duration of RTI by 0.77 days and reduce the risk for RTI (odds ratio 0.58). It may be surprising that the consumption of probiotics, which are thus interacting with the intestine, may have a benefit on respiratory health. Although the exact mechanism is not known, it is likely that modulation of the immune system plays a role here. Because of their ubiquitous nature, RTI carry a quite high financial burden. Not surprisingly, probiotics can provide substantial saving to health care and the individual by reducing RTI risk.
Primary prevention of atopic dermatitis
Atopic dermatitis (AD) is becoming increasingly more common in affluent societies. AD is most common during childhood and although most children grow out of it, it is associated with allergic diseases later in life; the so-called ‘atopic march’. There are thus short-term and long-term reasons to reduce the risk for AD. Probiotic consumption, starting with the expecting mother and continuing with the new born child, has consistently been shown to reduce the risk for AD (odds ratio 0.61). Interestingly, this benefit appears to extend for many years after probiotic consumption. Also, it is likely that probiotics contribute to a correct development of the immune system (i.e. tolerogenic). Savings can be substantial as benefits may last a lifetime.
Table 1. Examples of health benefits suggested for probiotics
|Health Benefit||Level of evidence||Comment|
|Reducing risk for antibiotic associated diarrhoea||Good||Numerous studies|
|Reducing risk for necrotising enterocolitis||Good||Numerous studies|
|Reducing risk for respiratory tract infections||Good||Numerous studies|
|Clostridium difficile associated diarrhoea||Good||Many studies|
|Prevention of atopy||Good||Many studies|
|Irritable bowel syndrome||Fair||Many studies not all positive|
|Inflammatory bowel disease||Fair||Many studies not all positive|
|Slow intestinal transit||Fair||Moderate effect|
|Serum cholesterol||Fair||Moderate effect|
|Bacterial vaginosis||Fair||Heterogeneous studies|
|Control of type-2 diabetes||Weak||Few studies|
|Gestational diabetes||Weak||Few studies|
|Periodontitis management||Weak||Few studies|
|Improving psychological symptoms/depression||Weak||Few studies|
|Adjunct to H. pylori eradication therapy||Weak||Few studies|
|Infantile colic||Weak||Few studies|
|Allergic rhinitis||Weak||Few studies|
|Blood pressure||Poor||Few studies not all positive|
|Dental caries||Poor||Few studies not all positive|
|Ventilator associated pneumonia||Poor||Few studies not all positive|
|Weight management||Poor||Few studies of poor quality|
|Cystic fibrosis||Poor||Few studies of poor quality|
|Urinary tract infection||Poor||Few studies of poor quality|
|Treatment of acute pancreatitis||No evidence||Few studies inconclusive results|
Probiotics can influence disease outcomes and risks; does this make them ‘drugs’? Most current probiotics would not qualify as drugs; while they may reduce risk for certain diseases, they do neither prevent them, nor do they cure them. This does not mean that there may not come a time that a specific probiotic would be considered as a drug.
What does this imply in practice? Would one recommend the use of probiotics, and if so, what product? Obviously, it is best to use products that have been studied for a specific health benefit one is targeting. However, with probiotics this may not always be straight forward. In which case, the best approach is to rely on products of good quality; products that report the strains and not just the species, the counts at the end of shelf life, etc. Furthermore, probiotics are among the safest dietary supplements with an extremely good safety record. The benefits may thus be substantial while the risks (and costs) are small or negligible.
About the Author
Dr Arthur Ouwehand is Technical Fellow and Research Manager at Active Nutrition in Kantvik, DuPont Nutrition & Health, Finland. He has a research background in both academia and industry. His main interest is on functional foods; in particular probiotics and prebiotics and their influence on the intestinal microbiota composition and activity. He is active in the International Life Sciences Institute Europe, the International Dairy Federation, the International Scientific Association for Probiotics and Prebiotics, the Global Alliance for Probiotics and the International Probiotic Association. Dr. Ouwehand received his M.Sc. degree (1992) in Cell Biology from Wageningen University (the Netherlands) and his Ph.D. degree (1996) in Microbiology from Göteborg University (Sweden). In 1999, he was appointed Adjunct Professor in Applied Microbiology at the University of Turku (Finland); since 2004 he has been working for Danisco; now DuPont Nutrition and Health. Dr. Ouwehand is the author of more than 250 journal articles and book chapters; he is the editor of three books on lactic acid bacteria and the intestinal microbiota and co-inventor on 13 approved patents.
About the The International Probiotics Association
The International Probiotics Association (IPA) is a global non-profit organization bringing together through its membership, the probiotic sector’s stakeholders including but not limited to academia, scientists, health care professionals, industry and regulators. The IPA’s mission is to be the unique platform where all these stakeholders can interact and collaborate to increase probiotic awareness amongst all users and help enable the industry’s sustainable growth. Holding NGO status before Codex Alimentarius, the IPA is also recognized as the unified “Global Voice of Probiotics” around the world.