Bifidobacterium animalis subsp. lactis in prevention of common infections in healthy children attending day care centers – Randomized, double blind, placebo-controlled study

doi:10.1016/j.clnu.2015.05.004

Clinical Nutrition

Volume 35, Issue 3, June 2016, Pages 587-591

https://doi.org/10.1016/j.clnu.2015.05.004 Get rights and content

Summary

Background & aims

The aim of our study was to investigate the role of Bifidobacterium animalis subsp. lactis (BB-12^®) in the prevention of common (gastrointestinal and respiratory) infections in healthy children who attend day care centers.

Methods

We conducted a randomized, double-blind, placebo-controlled trial in 210 children who attend day care centers. They were randomly allocated to receive placebo (Placebo group, n = 106) or BB-12^® at a dose of 10⁹ colony-forming units (CFU) (Intervention group, n = 104) during the 3-month intervention period.

Results

Intention to treat analysis was used. There were overall 99 infections in Placebo group and 97 in Intervention group (incidence rate ratio = 1.0014, p = 0.992, Poisson regression model). Overall 65 children (61.3%) in Placebo group and 67 (64.4%) in Intervention group had common infections (p = 0.642). Mean number of infections per child was 0.93 (range 0–3) in Placebo group and 0.93 (range 0–3) in Intervention group (p = 0.898). There was no difference in secondary (duration of symptoms, number of children with gastrointestinal and respiratory tract infections, absence from day care center due to infections, use of antibiotics) and exploratory (type of gastrointestinal and respiratory tract infection) endpoints between groups.

Conclusion

Results of performed study show that BB-12^® has no effect on the prevention of gastrointestinal and respiratory tract infections in healthy children who attend day care centers.

Introduction

Children who attend day care centers are at increased risk for acquiring acute infections which is2–3 times higher than in children who stay at home [1]. Beside increased number of infections, those children have more visits to primary care physician and emergency room, and use antibiotics more often [2]. This causes a significant economic burden for the family and society [1], [3], [4]. Therefore, it would be important to find a reliable strategy for the prevention of infections in those children. There are several studies investigating effect of probiotics on gastrointestinal and respiratory tract infections in healthy children [5], [6], [7], [8], [9], [10], [11]. We have also recently performed a randomized controlled trial (RCT) on the role of Lactobacillus rhamnosus GG (LGG^®) in the prevention of gastrointestinal and respiratory tract infections in children who attend day care center [6]. Results of the studies are more promising for respiratory tract infection than for gastrointestinal infections but the effect seems to be strain dependent.

Bifidobacterium animalis subsp. lactis (BB-12^®) is well known probiotic strain with proven safety and efficacy to prevent respiratory tract infection in infancy [12], but its ability to reduce infections in children attending day care centers was not yet investigated. Therefore, the aim of this study was to determine the role of a BB-12^® in prevention of the common infections in children who attend day care centers.

Section snippets

Study protocol

All children who attended day care centers located in 3 separate locations in the Zagreb area were eligible for the study. Socioeconomic background of those children was similar. Only children whose parents or legal guardians signed written informed consent and who did not meet any of the exclusion criteria were included into the study. Excluded children were those who were receiving probiotic and/or prebiotic products 2 weeks prior to or at the time of enrollment; those who had any severe

Demographics and other baseline characteristics

Overall data were analyzed for 106 children in Placebo group and 104 in Intervention group (Fig. 1). There was no significant difference in the demographic characteristics between the groups; median age was 4.6 years (mean 4.44 years; range 1.44–6.79 years) in Placebo group and median of 4.6 years (mean 4.49; range 1.43–7.48 years) in Intervention group (p = 0.92). There were 56 (52.8%) females in Placebo group and 58 (55.8%) in Intervention group (p = 0.669).

Product consumption was calculated

Discussion

Our study did not find an effect of the probiotic strain BB-12^® at a dose of 10⁹ CFU on the prevention of common infections in healthy children who attend day care center.

Emerging evidence clearly shows that the probiotic effect in the prevention or in the treatment of different diseases is strain dependent [13], [14]. The same applies for the prevention of respiratory and gastrointestinal infections in children attending day care centers [5], [6], [7], [8], [9], [10]. Significant preventive

Statement of authorship

Study concept and design: Hojsak and Kolaček. Acquisition of data: Hojsak, Močić Pavić, Kos, Dumančić. Analysis and interpretation of data: Hojsak, Kolaček. Drafting of the manuscript: Hojsak, Kolaček. Critical revision of the manuscript for important intellectual content: Hojsak, Močić Pavić, Kos, Dumančić, Kolaček. Administrative, technical, and material support: Hojsak, Močić Pavić, Kos, Dumančić.

Conflict of interest

None declared.

Funding

Study was funded by Chr. Hansen, Denmark.

Acknowledgements

We thank the staff of the Children day care centers Matija Gubec, Prečko and Remetinec in Zagreb for their great help with this study.

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Citation Excerpt :
B animalis subsp lactis BB12 given over a period of 3 months had no effect on the prevention of gastrointestinal and respiratory tract infections in healthy children who attended day care centres. Overall, the effect on the incidence of diarrhoea during the study period was not significant.32 In a community-based, double-blind, randomised controlled trial33 in India, children aged 1–3 years were randomly allocated to receive either control milk or the same milk fortified with 2·4 g per day of prebiotic oligosaccharide and 1·9 × 107 CFU per day of the probiotic B lactis HN019, resulting in significant reduction of dysentery, respiratory morbidity, and febrile illness.
The gastrointestinal microbiome is a hot topic in clinical research. Beneficial effects of selected probiotics in the prevention of gastrointestinal disorders are mainly restricted to acute gastroenteritis, antibiotic-associated diarrhoea, infantile colic, and necrotising enterocolitis. However, no broad consensus exists to recommend the use of probiotics in the prevention of these conditions, mainly because of the different design of the studies done so far, resulting in little evidence for specific strains, dosages, and indications. More well designed studies are needed before recommendations can be proposed. At this stage, the evidence is insufficient to recommend the routine use of probiotics in infants and children for the prevention of gastrointestinal disorders.
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2017, The Microbiota in Gastrointestinal Pathophysiology: Implications for Human Health, Prebiotics, Probiotics, and Dysbiosis
This chapter covers the use of probiotics in acute upper respiratory tract infections (URTI) and diarrheal diseases, such as acute gastroenteritis (AGE), antibiotic-associated diarrhea (AAD), and necrotizing enterocolitis (NEC).
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AAD: Randomized clinical trials and metaanalyses have concluded that in general probiotics (especially Lactobacillus GG, S. boulardii) were effective in reducing the risk of AAD, and also of Clostridium difficile-associated diarrhea.
NEC prevention: Clinical trials, mostly from Asia and Europe, have proven various probiotic preparations effective. Recent metaanalyses and position papers concurred that probiotics reduced the risk of NEC and related mortality.
Bifidobacterium animalis spp. lactis
2017, The Microbiota in Gastrointestinal Pathophysiology: Implications for Human Health, Prebiotics, Probiotics, and Dysbiosis
The species Bifidobacterium animalis populates the mammalian colon and grows well in milk; as a consequence, strains from these species have been isolated from milk cultures. Its resistance to acid and oxidative stress renders strains from these species ideally suited to their formulation in fermented milk products. Laboratory studies have identified a number of properties that could be clinically relevant: immune modulation, epithelial adherence, and enhancement of gut barrier function. Two commercially available strains have been studied extensively: B. animalis spp. lactis BB-12 and B. animalis spp. lactis DN-173 010. The latter has been shown to accelerate gut transit in man and to provide symptom relief to individuals with common gastrointestinal symptoms, irritable bowel syndrome and constipation, while the former has shown some promise in boosting the immune response in man.
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In parallel, the production of sIgA, a relevant component of acquired immunity, resulted positively affected by the two fermented dietary products. Similar results have been reported in several studies investigating probiotics or synbiotics [3,10–12]. In the present study killed probiotic was used.
Fermented foods have been proposed for the prevention of infectious diseases. We evaluated the efficacy of fermented foods in reducing common infectious diseases (CIDs) in children attending daycare.
Prospective randomized, double-blind, placebo-controlled trial (registered under Clinical Trials.gov identifier NCT01909128) on healthy children (aged 12–48 months) consuming daily cow's milk (group A) or rice (group B) fermented with Lactobacillus paracasei CBA L74, or placebo (group C) for three months during the winter season. The main study outcome was the proportion of children who experienced at least one CID. All CIDs were diagnosed by family pediatricians. Fecal concentrations of innate (α- and β-defensins and cathelicidin LL-37) and acquired immunity biomarkers (secretory IgA) were also evaluated.
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Dietary supplementation with cow's milk or rice fermented with L. paracasei CBA L74 prevents CIDs in children attending daycare possibly by means of a stimulation of innate and acquired immunity.

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^☆: This trial has been registered at ClinicalTrials.gov (NCT01702753).

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Randomized control trialsBifidobacterium animalis subsp. lactis in prevention of common infections in healthy children attending day care centers – Randomized, double blind, placebo-controlled study☆

Summary

Background & aims

Methods

Results

Conclusion

Introduction

Section snippets

Study protocol

Demographics and other baseline characteristics

Discussion

Statement of authorship

Conflict of interest

Funding

Acknowledgements

Clin Nutr

Am J Clin Nutr

Vaccine

Child day care risks of common infectious diseases revisited

Child Care Health Dev

Health care utilization and expenditures associated with child care attendance: a nationally representative sample

Pediatrics

Illnesses and absence due to illness among children attending child care facilities in Seattle-King County, Washington

Pediatrics

Respiratory illness in children attending daycare

Pediatr Pulmonol

Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial

BMJ

Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents

Pediatrics

Randomized control trials
Bifidobacterium animalis subsp. lactis in prevention of common infections in healthy children attending day care centers – Randomized, double blind, placebo-controlled study☆