Effect of Lactobacillus paracasei subsp. paracasei, L. casei 431 on immune response to influenza vaccination and upper respiratory tract infections in healthy adult volunteers: a randomized, double-blind, placebo-controlled, parallel-group study.
BACKGROUND
Probiotics can modulate the immune system in healthy individuals and may help reduce symptoms related to respiratory infections.


OBJECTIVE
The objective of the study was to investigate the effect of the probiotic strain Lactobacillus paracasei subsp. paracasei, L. casei 431 (Chr. Hansen A/S) (hereafter, L. casei 431) on immune response to influenza vaccination and respiratory symptoms in healthy adults.


METHODS
A randomized double-blind, placebo-controlled trial was conducted in 1104 healthy subjects aged 18-60 y at 2 centers in Germany and Denmark. Subjects were randomly assigned to receive an acidified milk drink containing ≥10(9) colony-forming units of L. casei 431 (n = 553) or placebo (n = 551) for 42 d. After 21 d, subjects received the seasonal influenza vaccination. The primary outcome was seroprotection rate (anti-influenza antibody titers by hemagglutination inhibition) 21 d after vaccination. Other outcomes were seroconversion rate and mean titers, influenza A-specific antibodies and incidence, and duration and severity of upper respiratory symptoms. Antibiotic use and use of health care resources were recorded.


RESULTS
There was no effect of L. casei 431 on immune responses to influenza vaccination. Generalized linear mixed modeling showed a shorter duration of upper respiratory symptoms in the probiotic group than in the placebo group (mean ± SD: 6.4 ± 6.1 vs. 7.3 ± 9.7 d, P = 0.0059) in the last 3 wk of the intervention period. No statistically significant differences were found for incidence or severity.


CONCLUSIONS
Daily consumption of L. casei 431 resulted in no observable effect on the components of the immune response to influenza vaccination but reduced the duration of upper respiratory symptoms. The trial was registered at www.isrctn.com as ISRCTN08280229.
From Chr. Hansen A/S, Hørsholm, Denmark (LJ, IT, DE, CMM, and BM); Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark (SB and LOD); Department of Sciences, Roosevelt Academy, Middelburg, The Netherlands (GTR); Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, and National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom (PCC).
Lillian
L
Jespersen
From Chr. Hansen A/S, Hørsholm, Denmark (LJ, IT, DE, CMM, and BM); Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark (SB and LOD); Department of Sciences, Roosevelt Academy, Middelburg, The Netherlands (GTR); Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, and National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom (PCC).
Inge
I
Tarnow
From Chr. Hansen A/S, Hørsholm, Denmark (LJ, IT, DE, CMM, and BM); Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark (SB and LOD); Department of Sciences, Roosevelt Academy, Middelburg, The Netherlands (GTR); Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, and National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom (PCC).
Dorte
D
Eskesen
From Chr. Hansen A/S, Hørsholm, Denmark (LJ, IT, DE, CMM, and BM); Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark (SB and LOD); Department of Sciences, Roosevelt Academy, Middelburg, The Netherlands (GTR); Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, and National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom (PCC). dkcmm@chr-hansen.com.
Cathrine Melsaether
CM
Morberg
From Chr. Hansen A/S, Hørsholm, Denmark (LJ, IT, DE, CMM, and BM); Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark (SB and LOD); Department of Sciences, Roosevelt Academy, Middelburg, The Netherlands (GTR); Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, and National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom (PCC).
Birgit
B
Michelsen
From Chr. Hansen A/S, Hørsholm, Denmark (LJ, IT, DE, CMM, and BM); Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark (SB and LOD); Department of Sciences, Roosevelt Academy, Middelburg, The Netherlands (GTR); Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, and National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom (PCC).
Susanne
S
Bügel
From Chr. Hansen A/S, Hørsholm, Denmark (LJ, IT, DE, CMM, and BM); Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark (SB and LOD); Department of Sciences, Roosevelt Academy, Middelburg, The Netherlands (GTR); Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, and National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom (PCC).
Lars Ove
LO
Dragsted
From Chr. Hansen A/S, Hørsholm, Denmark (LJ, IT, DE, CMM, and BM); Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark (SB and LOD); Department of Sciences, Roosevelt Academy, Middelburg, The Netherlands (GTR); Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, and National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom (PCC).
Ger T
GT
Rijkers
From Chr. Hansen A/S, Hørsholm, Denmark (LJ, IT, DE, CMM, and BM); Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark (SB and LOD); Department of Sciences, Roosevelt Academy, Middelburg, The Netherlands (GTR); Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, and National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom (PCC).
Philip C
PC
Calder
D000293:Adolescent; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015992:Body Mass Index; D015169:Colony Count, Microbial; D003718:Denmark; D004311:Double-Blind Method; D005260:Female; D005858:Germany; D064368:Healthy Volunteers; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000627:therapeutic use; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D007780:Lacticaseibacillus casei; D008297:Male; D008875:Middle Aged; D008892:Milk; D019936:Probiotics / Q000008:administration & dosage*; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control*; D016896:Treatment Outcome; D014611:Vaccination; D055815:Young Adult
D000914:Antibodies, Viral; D007252:Influenza Vaccines
L. casei 431; Lactobacillus paracasei subsp. paracasei; immune function; probiotics; upper respiratory tract infection; vaccination response