Prebiotics and probiotics

Should I give my baby pre- or probiotics?

Prebiotics promote the growth of good bacteria, while probiotics are the good bacteria themselves. Both are naturally present in breast milk. Commercially-produced prebiotics and probiotics are heavily promoted, but there are concerns about their safety and there is conflicting and limited evidence to support their use. Suggested benefits of probiotics include lower rates of a serious bowel disease and fewer blood infections in premature babies and prevention of side-effects caused by antibiotics and acid-suppressing medication when these are used by children. There are limited, varying standards and regulations around the manufacturing, labelling, and advertising of these items. Commercial preparations may not contain live probiotics, may have labelling inconsistencies and deviations, or be contaminated.

A) Describing commercial prebiotics and probiotics

Commercial prebiotics and probiotics aim to increase the number of good bacteria in a person’s microbiome, the community of microbes that live in and on the body.

1) Prebiotics

A prebiotic is an agent, usually a type of sugar such as a human milk oligosaccharide (HMO), that helps good bacteria grow. Prebiotics are like fertilizer for good bacteria. 

There are more than 200 types of HMOs in human milk. The effectiveness of prebiotics found in human milk may depend on their personalized nature and on their combination into specific ratios.

By comparison, there are only a small number of commercially-produced prebiotics (Bode 2016; Moore 2021). Commercial probiotics are either extracted from animal tissues, which have problems such as unstable sources of raw materials, potential allergens, or contaminants or they are harvested from bacteria in large-scale industrial processes.

2) Probiotics

A probiotic is a good bacterium or inactivated parts of one, given to improve health.

Human milk has been reported to have up to 700 species of bacteria and the gut has roughly 2000 (Almeida 2019). The types of gut bacteria are unique to each baby and are partially determined by various components in breast milk (Lackey 2019; Moossavi 2019). In contrast, only a small number of probiotic bacteria strains are commercially produced.

3) The industry

Pre- and probiotics are a multibillion-dollar industry and their sales have been increasing steadily in the past decade. Research studies have mirrored this increase. Probiotic research started around 1998 and by 2018, there were roughly 20,000 studies (Day 2019). However, results of studies have been contradictory and clear proof about the safety and effectiveness of commercial prebiotics and probiotics is still lacking (Day 2019; Valdenpla 2019).

In spite of this, commercial prebiotics and probiotics are heavily promoted for prevention and treatment of a large variety of illnesses and for the optimization of body function (Di Cerbo 2015; Leite 2019). Pre- and probiotics have also been promoted for mothers and babies. There is not enough evidence to recommend the addition of pre- or probiotics to infant formula.

B) Evidence for the use of commercial probiotics

Various studies have found that commercial probiotics may:

  • Prevent necrotizing enterocolitis (NEC), blood infections, and death in premature babies (Morgan 2020; van den Akker 2020).
  • Reduce asthma severity (Vandenplas 2019).
  • Reduce the amount of crying in babies (Ong 2019).
  • Reduce the risk of diarrhea and a certain type of bacterial gut infection (C. difficile) that develops when individuals use antibiotics (Goldenberg 2017; Gray 2019; Madoff 2020; Szajewska 2016).
  • Shorten the duration of stomach infections (Szajewska 2014).
  • Mitigate the negative effects of acid-suppressing medication on gut bacteria when used for the treatment of GERD (Belei 2018).
  • Prevent ear infections in children not prone to them (Scott 2019).
  • Prevent mastitis in breastfeeding mothers.
  • Treat subacute mastitis

However the evidence has many limitations. Studies of probiotics may (Day 2019; Navarro-Tapia 2020; Parker 2018; Suez 2019:

  • Not specify which probiotic species, strain, dose, manufacturing processes, and storage conditions were used.
  • Only look at small numbers of individuals or be poorly designed.
  • Only follow individuals for short periods of time.
  • Not measure results of probiotic use in a standardized manner.
  • Report conflicting results about probiotic strains and preparations.
  • Not be able to assess how each individual’s unique microbiome is affected by probiotics.
  • Have authors with conflicts of interest (Amir 2016).

C) Safety and effectiveness

Many products, including foods, dietary supplements, and pharmaceuticals, are described as probiotic. They are perceived as safe, natural, and health-promoting, but this is not always the case. The standards and regulations for these products vary, which leads to safety concerns (Jackson 2019; de Simone 2019).

The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition has raised concerns about the manufacturing and labelling of probiotics (Kolaček 2017). This group of pediatric specialists said:

  • Inconsistencies and deviations from the information provided on the product label are surprisingly common.
  • Strains of probiotics were misidentified and misclassified.
  • The products were occasionally contaminated (Vermeulen 2019).
  • Sometimes the bacteria strains were no longer alive and would be unable to provide any benefits.

The safety and effectiveness of probiotics may also depend on the:

  • Amount and dosage.
  • Particular strain of probiotic bacteria.
  • Preparation and storage (Watkins 2018).
  • Health and characteristics of the person taking them (Sotoudegan 2019).
  • Reason for taking them (Hojsak 2017).

Probiotics given to children may cause severe infections in those with a weakened immune system (Mantegazza 2018). There is a concern that probiotics may increase resistance to some antibiotics (Mantegazza 2018; Topcuoglu 2015). Long-term effects are poorly studied but may be significant (Quin 2018).

References

Almeida A, Mitchell AL, Boland M, et al. A new genomic blueprint of the human gut microbiota. Nature. 2019 Apr;568(7753):499-504

Amir LH, Griffin L, Cullinane M, et al. Probiotics and mastitis: evidence-based marketing? International Breastfeeding Journal. 2016;11:19  

Belei O, Olariu L, Dobrescu A, et al. Is It Useful to Administer Probiotics Together With Proton Pump Inhibitors in Children With Gastroesophageal Reflux? J Neurogastroenterol Motil. 2018 Jan 30;24(1):51-57

Bode L, Contractor N, Barile D, et al. Overcoming the limited availability of human milk oligosaccharides: challenges and opportunities for research and application.  Nutr  Rev. 2016 Oct;74(10):635-44  

Chi C, Li C, Buys N, Wang W, Yin C, Sun J. Effects of Probiotics in Preterm Infants: A Network Meta-analysis. Pediatrics. 2020 Dec 15:e20200706

Day RL, Harper AJ, Woods RM, et al. Probiotics: current landscape and future horizons. Future Sci OA. 2019 May 3;5(4):FSO391
 
de Simone C. The Unregulated Probiotic Market. Clin Gastroenterol Hepatol. 2019 Apr;17(5):809-817.
 
Di Cerbo A, Palmieri B. Review: The market of probiotics. Pak J Pharm Sci. 2015 Nov;28(6):2199-206
 
Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017 Dec 19;12:CD006095
 
Gray C, Dulong C, Argáez C. Probiotics for Antibiotic-Associated Diarrhea in Pediatrics: A Review of Clinical Effectiveness and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Mar 25
 
Hojsak I. Probiotics in Children: What Is the Evidence? Pediatr Gastroenterol Hepatol Nutr. 2017 Sep;20(3):139-146

Jackson SA, Schoeni JL, Vegge C, et al. Improving End-User Trust in the Quality of Commercial Probiotic Products. Front Microbiol. 2019 Apr 17;10:739
 
Kolaček S, Hojsak I, Canani RB, et al.; ESPGHAN Working Group for Probiotics and Prebiotics. Commercial Probiotic Products: A Call for Improved Quality Control. A Position Paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2017 Apr 11
 
Lackey KA, Williams JE, Meehan CL, et al. What's Normal? Microbiomes in Human Milk and Infant Feces Are Related to Each Other but Vary Geographically: The INSPIRE Study. Front Nutr. 2019 Apr 17;6:45
 
Leite GSF, Resende Master Student AS, West NP, et al. Probiotics and sports: A new magic bullet? Nutrition. 2019 Apr;60:152-160
 
Madoff SE, Urquiaga M, Alonso CD, et al. Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials. Anaerobe. 2020 Feb;61:102098
 
Mantegazza C, Molinari P, D'Auria E, et al. Probiotics and antibiotic-associated diarrhea in children: A review and new evidence on Lactobacillus rhamnosus GG during and after antibiotic treatment. Pharmacol Res. 2018 Feb;128:63-72

Moore RE, Xu LL, Townsend SD. Prospecting Human Milk Oligosaccharides as a Defense Against Viral Infections. ACS Infect Dis. 2021 Feb 12;7(2):254-263

Moossavi S, Atakora F, Miliku K, et al. Integrated Analysis of Human Milk Microbiota With Oligosaccharides and Fatty Acids in the CHILD Cohort. Front Nutr. 2019 May 16;6:58

Morgan RL, Preidis GA, Kashyap PC, et al.; McMaster Probiotic, Prebiotic, and Synbiotic Work Group. Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-analysis of Randomized Trials. Gastroenterology. 2020 Aug;159(2):467-480

Navarro-Tapia E, Sebastiani G, Sailer S, et al. Probiotic Supplementation During the Perinatal and Infant Period: Effects on Gut Dysbiosis and Disease. Nutrients. 2020 Jul 27;12(8):E2243
 
Ong TG, Gordon M, Banks SS, et al. Probiotics to prevent infantile colic. Cochrane Database Syst Rev. 2019 Mar 13;3:CD012473
 
Parker EA, Roy T, D'Adamo CR, et al. Probiotics and gastrointestinal conditions: An overview of evidence from the Cochrane Collaboration. Nutrition. 2018 Jan;45:125-134.e11
 
Quin C, Estaki M, Vollman DM, et al. Probiotic supplementation and associated infant gut microbiome and health: a cautionary retrospective clinical comparison. Sci Rep. 2018 May 29;8(1):8283
  
Scott AM, Clark J, Julien B, et al. Probiotics for preventing acute otitis media in children. Cochrane Database Syst Rev. 2019 Jun 18;6:CD012941
 
Sotoudegan F, Daniali M, Hassani S, et al. Reappraisal of probiotics' safety in human. Food Chem Toxicol. 2019 Jul;129:22-29
 
Suez J, Zmora N, Segal E, et al. The pros, cons, and many unknowns of probiotics. Nat Med. 2019 May;25(5):716-729
 
Szajewska H, Canani RB, Guarino A, et al.; ESPGHAN Working Group for ProbioticsPrebiotics. Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Children. J Pediatr Gastroenterol Nutr. 2016 Mar;62(3):495-506.
 
Szajewska H, Guarino A, Hojsak I, et al.; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2014 Apr;58(4):531-9.
 
Topcuoglu S, Gursoy T, Ovali F, et al. A new risk factor for neonatal vancomycin-resistant Enterococcus colonisation: bacterial probiotics. J Matern Fetal Neonatal Med. 2015;28(12):1491–1494

van den Akker CHP, van Goudoever JB, Shamir R, et al. Probiotics and Preterm Infants: A Position Paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition and the European Society for Paediatric Gastroenterology Hepatology and Nutrition Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2020 May;70(5):664-680

Vandenplas Y, Savino F. Probiotics and Prebiotics in Pediatrics: What Is New? Nutrients. 2019 Feb 19;11(2). pii: E431
 
Vermeulen MJ, Luijendijk A, van Toledo L, et al. Quality of probiotic products for preterm infants: contamination and missing strains. Acta Paediatr. 2019 Aug 18
 
Watkins C, Murphy K, Dempsey EM, et al. The viability of probiotics in water, breast milk, and infant formula. Eur J Pediatr. 2018 Apr 2