Safety of the use of probiotics
The use of oral probiotics has been well researched in many different (incl. vulnerable) patient populations, including infants, elderly people and immunocompromised patients. The general conclusion is that there are no safety risks for the studied bacterial strains in the dosages that were used in the studies. Caution is recommended in a number of highly vulnerable patient populations, such as oncology patients with severe leukopenia or mucositis. Probiotics use in acute pancreatitis is contraindicated.
Administering probiotics via a (PEG) feeding tube in the stomach is possible, but we advise against administering probiotics beyond the stomach.
The use of probiotics is increasing, even in vulnerable patient groups. This may elicit questions about their safety. However, recent studies into the use of probiotics have not revealed any safety risks. This not only applies to healthy adults, but also to infants, children, elderly people and immunocompromised patients, such as HIV patients, donor organ recipients and patients with autoimmune diseases. 123
Concerns about the safety of probiotics in patients with serious illnesses have mainly been instigated by the PROPATRIA 4 studyiv (2008), in which patients with severe pancreatitis were tube-fed directly into the intestine. However, the study set-up was criticized and later studies did not indicate probiotics would have been the cause of the higher mortality rate in this population. 56
Probiotics on the “safe list”
The European Food Safety Authority (EFSA) assesses the safety of micro-organisms for use as food additives and other specific aims. Each year, the EFSA evaluates new scientific data. The species and strains found to be safe are on the Qualified Presumption of Safety (QPS) list (comparable to the Generally Recognized as Safe (GRAS) list of the American Food and Drug Administration (FDA)).7 Winclove uses bacterial strains that are entered on the QPS list. For any strains not on the QPS list, an extensive safety file must be submitted. This has been done for the strains of E. faecium and S. oralis in accordance with EFSA guideline.
Babies and children
Van den Nieuwboer et al. published two meta-analyses, in 2014 and 2015, about the use of probiotics in babies (aged 0-2)8 and children up to 18 years of age.9 131 studies were analysed, involving a total of 14,115 children. These studies included a diverse paediatric population, including healthy children, obese children, children with elevated allergy risks, preterm babies and children with digestive disorders such as diarrhoea, cramps, chronic constipation and acid reflux. A great variety of probiotics was researched with an average daily dose of 3-4 × 109 CFU. The conclusion that can be drawn from the analyses is that all studied probiotic strains are safe for use. In children up to 18 years of age, most of the “side effects” were even seen in the placebo group.
At this time, no meta-analyses are available about the safety of using probiotics in elderly individuals. What we do have is a considerable number of studies involving elderly subjects, focusing on antibiotics-associated diarrhoea, constipation and reducing infections. The findings of 12 studies have been summarized in the systematic review by Rondanelli et al., the conclusions of which include that elderly people can safely use probiotics.10 In a recent study into the effect of Lactobacillus casei Shirota (LcS) on the digestion of vulnerable elderly people of very advanced age (74-99 years) in care homes, no safety risks were identified.11
In 2015, Van den Nieuwboer et al. published a meta-analysis about the use of probiotics in immunocompromised patients,12 defined as individuals infected with HIV, people with a severe illness, people who recently underwent surgery and people with an organ or autoimmune disease. 57 studies were analysed, involving a total of 2,563 patients. A great variety of probiotics was researched with an average daily dose of 2 × 109 CFU. The conclusion is that use of the studied probiotics strains in this patient group is considered safe.
Oral use of probiotics is safe for immunodeficient patients, such as HIV patients, donor organ recipients and patients with autoimmune diseases – that is also the conclusion of an opinion statement in Beneficial Microbes (2015).13
When is caution recommended?
The many studies into probiotics all conclude that they can be used safely. In a number of vulnerable patient groups, including oncology patients with severe leukopenia and mucositis, the use of probiotics has either not been studied adequately or not at all. For that reason, Winclove is unable to make any statements about the safety for entire patient populations. Healthcare professionals are advised to use a case-by-case approach when considering whether or not to use probiotics.
When using a (PEG) feeding tube, Winclove recommends to only administer probiotics if the tube is in the stomach. Note: In the aforementioned PROPATRIA study,(4) the feeding tube had been inserted beyond the stomach.
- 1. Van den Nieuwboer M, Brummer RJ, Guarner F, Morelli L, Cabana M, Claassen E. Safety of probiotics and synbiotics in children under 18 years of age. Benef Microbes. 2015;6(5):615-30. doi: 10.3920/BM2014.0157.
- 2. Van den Nieuwboer M, Brummer RJ, Claasen E et al. The administration of probiotics and synbiotics in immune compromised adults: is it safe? Benef Microbes. 2015 Mar;6(1):3-17. doi: 10.3920/BM2014.0079.
- 3. Van den Nieuwboer M, Claassen E, Morelli L, Guarner F, Brummer R. Probiotic and synbiotic safety in infants under two years of age. Beneficial microbes. 2014;5(1):45-60. doi: 10.3920/BM2013.0046.
- 4. Besselink MG, Van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Rosman C, Ploeg RJ, Brink MA, Schaapherder AF, Dejong CH, Wahab PJ, van Laarhoven CJ, van der Harst E, van Eijck CH, Cuesta MA, Akkermans LM, Gooszen HG; Dutch Acute Pancreatitis Study Group. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Feb 23;371(9613):651-9. doi: 10.1016/S0140-6736(08)60207-X.
- 5. Morrow LE, Gogineni V, Malesker MA. Synbiotics and probiotics in the critically ill after the PROPATRIA trial. Curr Opin Clin Nutr Metab Care. 2012 Mar;15(2):147-50. doi: 10.1097/MCO.0b013e32834fcea8. Review. PMID: 22248590.
- 6. Van Baal, M.C.P.M. Acute pancreatitis : persisting issues from the PROPATRIA and PANTER studies. PhD thesis, Radboud University Nijmegen, The Netherlands, 2014.
- 7. Scientific Opinion on the maintenance of the list of QPS biological agents intentionally added to food and feed (2013 update). EFSA Journal 2013;11(11):3449 [106 pp.].
- 8. Van den Nieuwboer M, Claassen E, Morelli L, Guarner F, Brummer R. Probiotic and synbiotic safety in infants under two years of age. Beneficial microbes. 2014;5(1):45-60.
- 9. Van den Nieuwboer M, Brummer R, Guarner F, Morelli L, Cabana M, Claassen E. Safety of probiotics and synbiotics in children under 18 years of age. Beneficial microbes. 2015:1-16.
- 10. Rondanelli M, Giacosa A, Faliva MA, Perna S, Allieri F, Castellazzi AM. Review on microbiota and effectiveness of probiotics use in older. World J Clin Cases. 2015 Feb 16;3(2):156-62. doi: 10.12998/wjcc.v3.i2.156.
- 11. Van den Nieuwboer M, Klomp-Hogeterp A, Verdoorn S, Metsemakers-Brameijer L, Vriend TM, Claassen E, Larsen OF. Improving the bowel habits of elderly residents in a nursing home using probiotic fermented milk. Benef Microbes. 2015;6(4):397-403. doi: 10.3920/BM2014.0113.
- 12. Van den Nieuwboer M, Brummer RJ, Claasen E et al. The administration of probiotics and synbiotics in immune compromised adults: is it safe? Benef Microbes. 2015 Mar;6(1):3-17. doi: 10.3920/BM2014.0079.
- 13. Stadlbauer V. Immunosuppression and probiotics: are they effective and safe? Beneficial microbes. 2015:1-6. doi: 10.3920/BM2015.0065.