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. 2011 Sep 30;3(1):91–129.

Table 5.

Effect of probiotics on immune function

Subjects N Intervention Findings Reference
Animals        
Female Balb/c mice, 7 wk and 19 mo 8/10 (C)
8/10 (PB)		 Live L. bulgaricus
+S.thermophilus (4x108 CFUs, each) for 7 d

  • -Increase IFN-α production by LPS-induced splenocytes and IFN-γ production by Con A-stimulated splenocytes

 Muscettola et al. 1994 [152]
Balb/c mice, 6 wk 5 (C)
5x6 (PB)		 Live W. kimchii, L. fermentum, L. plantarum (107 CFUs/d, each or 109 CFUs/d, each) for 3 wk

  • -Enhance phagocytic capacity of peritoneal leukocytes against FITC-labeled E. coli

  • -Heat-killed PB did not increase the phagocytic activity

 Lee and Lee, 2005 [163]
Male C57BL/6 mice, 20 mo Complete
6 (C)
6 (PB)
Low protein
8 (C)
8 (PB)		 L. johnsonii La1 (≥1x109 CFUs/d) for 14 d In complete diet

  • -Increase DT specific IgA and total IgA in fecal extract

  • -Decrease TNF-α production by LPS-stimulated splenocytes

  • -No effect on serum DT-specific IgA and IgG, splenocytes proliferation, proportion of CD4+ and CD8+

In low protein diet

  • -Increase DT specific IgA and total IgA in fecal extract

  • -Increase serum DT-specific IgG, total IgA,

  • -Increase % CD8+, Con A-induced lymphocyte proliferation

 Kaburagi et al. 2007 [161]
Balb/c mice, 6–8 wk 6 (C)
6x6 (PB)		 L. paracasei subsp. paracasei NTU 101 (108 CFUs/d) for 3, 6, 9 wk

  • -Upregulate DC maturation markers (MHC-II, CD80, CD86)

  • -Increase serum IgG -Increase NKG2D involved in NK cell cytotoxicity and lymphocyte proliferation

 Tsai et al. 2008 [164]
Male C57BL/6 mice, 21 mo 10 (C)
15 (PB)
15 (S)		 PB: L. paracasei NCC2461 (1x109 CFUs/d)
S: L. paracasei NCC2461 (1x109 CFUs/d) + fructo-oligosaccharide+inulin, given in the drinking water for 44 d		 Immunized on day 15 and challenged on day 22 with keyhole limpet hemocyanin (KLH)

  • -Increase Th1 cell-dependent immune responses such as anti-KLH IgG2a and DTH response and a trend towards increased anti-KLH IgG1

  • -No effect on splenocyte proliferation, T cell subsets, systemic total IgG, mucosal total IgA, Con A-stimulated cytokine production (IL-2, IFN-γ, IL-4)

  • -No additional effect of fructo-oligosaccharide and inulin

 Vidal et al. 2008 [157]
Balb/c mice, 6–9 wk 10 (C)
6x10 (PB)		 Live B. adolescentis BBMN23,
B. longum BBMN68 (2x107, 2x109 or 2x1011 CFUs /kg BW) for 4 wk		 Two Bifidobacterium strains isolated from healthy centenarians in China

  • -Increase NK cell activity in BBMN23 starting 2x109 CFUs/kg BW and in BBMN68 starting at 2x107 CFUs/kg and lymphocyte proliferation in all BBMN23 and BBMN68 groups

  • -Increase serum lysozyme and phagocytic activity of MΦ in all PB groups

 Yang et al. 2009 [162]
Female Kunming mice, 2 mo and 20 mo Young
20 (C)
Old
20 (C)
20 (PB)		 B. bifidum (5x108 CFUs/d) for 8 wk

  • -Increase thymus weight relative to the final BW

  • -Decrease serum TNF-α and IL-6

  • -Increase IL-2 and IFN-α production in Con A-stimulated splenocytes

 Fu et al. 2010 [158]
Female C57BL/6 mice, 4–6 wk 12 (C)
2x12 (PB)		 Heat killed L. bulgaricus OLL1181 (109 CFUs/d) or L. caseri MEP222701 (109 CFUs/d) for 8–11 d starting 7 d prior to colitis induction

  • -L. bulgaricus OLL1181 increases percentage of survival from dextran sodium sulfate-induced colitis and COX-2 mRNA expression in the colon

  • -L. bulgaricus OLL1181 decreases inflammation score, TNF-α and myeloperoxidase mRNA expression in the colon

 Takamura et al. 2011 [265]
Humans        
Healthy male, 40–65 y 10 (P)
10 (PB)		 P: unfermented milk
PB: L. casei (>1011 CFUs/d) fermented milk for 4 wk

  • -No change in lymphocyte population, humoral parameters, NK activity, cytokine production (IFN-γ, IL-1β, IL-2), phagocytic capacity, oxidative burst and DTH response

 Spanhaak et al. 1998 [179]
Healthy adults, 22–50 y 9 into (P), (PB) P: milk
PB: L. GG (2.6x108 CFUs/d) for 1 wk

  • -Increase expression of phagocytosis receptors (CRI, CRI3, FcγRIII, and FcαR) on neutrophil

 Pelto et al. 1998 [171]
Healthy adults, 20–50 y 9 (P)
10/10 (PB)		 L. GG (4x1010 CFUs/d) or
L. lactis (3.4x1010 CFUs/d) for 7 d		 All subjects received attenuated Salmonella typhi oral vaccine on day 1, 3, and 5

  • -No effect on humoral response (IgA, IgG and IgM)

  • -Increase CR3 receptor expression on neutrophils in L. lactis group

 Fang et al. 2000 [170]
Healthy, 41–81 y 27/23 (PB) B. lactis HN019 (5x1010 CFUs/d) in low fat milk/or in lactose-hydrolysed low fat milk for 3 wk

  • -Increase PMN cell phagocytic activity and NK cell tumor killing activity

  • -Greater effect of B. lactis in lactose-hydrolysed low fat milk on phagocytic activity and NK cell cytotoxicity

 Chiang et al. 2000 [172]
Healthy elderly, >60 y 12 (P)
13 (PB)		 Live B. lactis HN019 (3x1011 CFUs/d) for 6 wk

  • -Increase IFN-α production by Con A-stimulated PBMC

  • -Enhance phagocytic activity of PMN cells

 Arunachalam et al. 2000 [167]
Healthy, 44–80 y 25/27 (PB) L. rhamnosus (5x1010 CFUs/d) in low fat milk /or in lactose-hydrolysed low fat milk for 3 wk

  • -Increase PMN cell phagocytic activity and NK cell tumor killing activity

  • -Greater effect of L. rhamnosus in lactose-hydrolysed low fat milk on NK cell activity

 Sheih et al. 2001 [173]
Healthy elderly, 60–84 y 27 (PB) L. rhamnosus HN001 (5x1010 CFUs/d) or B. lactis HN019 (5x109 CFUs/d) for 3 wk

  • -Increase NK cell in PBMC

  • -Increase tumoricidal activity of PBMC

  • -More pronounced improvement in tumoricidal activity of PBMC isolated from subjects >70 y

 Gill et al. 2001 [168]
Healthy elderly, 64–84 y 29 (PB) B. lactis HN019 (low dose, 5x109 CFUs/d or typical dose, 5x1010 CFUs/d) for 3 wk

  • -Increase percentage of CD3+, CD4+, CD25+, NK cells, but no change in CD8+, B cells, MHC-II bearing APC

  • -Increase phagocytic activity of PBMC and PMN cells

  • -Greater improvement in phagocytic activity in subjects supplemented with typical dose and poor immune response before intervention

 Gill et al. 2001 [169]
Healthy adults, 51–58 y 22 (P)
23 (PB)		 L. casei DN114001 for 8 wk

  • -Increase oxidative burst capacity of monocytes and NK cell tumoricidal activity

 Parra et al. 2004 [174]
Healthy adults, 18–62 y 20 (P)
7x9 (PB)		 B. lactis Bi-07, B. lactis Bl-04, L. acidophilus La-14, L. acidophilus NCFM®, L. plantarum Lp-115, L. salivarius Ls-33, L. paracasei Lpc-37; Each group received one of 7 different strains (1010 CFU/d) for 3 wk

  • -No difference in specific IgA against oral cholera vaccine in saliva samples among groups

  • -Increase serum IgG in B. lactis Bl-04 group and L. acidophilus La-14 group

 Paineau et al. 2008 [266]
Healthy adults, 23–58 y 16 (P)
13/16/17 (PB)		 L. rhamnosus GG (1.6x1010 CFUs/d), B. animalis ssp. Lactis Bb12 (3.5x1010 CFUs/d), P. freudenreichii ssp. Shermanii JS (3.3x1010 CFUs/d) for 3 wk

  • -No effect on lymphocytes population, serum cytokine, serum Ig and secretory IgA in saliva

  • -Decrease ex vivo TNF-α production in response to Streptococcus in L. GG group and ex vivo IL-2 production in response to Influenza in Bb12 group

 Kekkonen et al. 2008 [178]
Nursing home elderly, mean age 84.3±0.98 y 86 (C)
67 (P)
56 (PB)		 C: commercial fermented oat drink containing B. animalis ssp lactis Bb-12 (109 CFUs/d)
P: oat-based drink
PB: oat-based drink with B longum 2C and 46 (109 CFUs/d, each) for 6 mo

  • -Modulate fecal B. species

  • -Increase TGF-β1 in all three groups

  • -Negative correlations between levels of B. species and cytokines (TNF-α and IL-10)

 Ouwehand et al. 2008 [267]
Elderly, regularly using non-steroidal anti-inflammatory drugs, >65 y 23 (P)
24 (PB)		 L. acidophilus (≥1010 CFUs/d) + lactitol for 2 wk

  • -Transient increase in B. levels during intervention

  • -Increase feacal IgA, but no difference between P and PB

  • -Increase faecal PGE2

  • -No effect on faecal TNF-α

 Ouwehand et al. 2009 [268]
Healthy nursing home elderly, >70 y 44 (P)
42 (PB)
113 (P)
109 (PB)		 P: non-fermented control dairy product for 7 wk or 13 wk
PB:L. casei DN-114 001 (≥2x1010 CFUs/d) + S. thermophilus and L. bulgaricus (≥2x1010 CFUs/d) as fermented dairy drink (Actimel®) for 7 wk or 13 wk

  • -Tend to improve humoral response after 7 wk supplementation, but not significant

  • -Improve humoral response (Ab titer against influenza vaccine and seroconversion) after 13 wk supplementation

 Boge et al. 2009 [176]
Healthy elderly, 61–94 y 13 SNH (PB)
23 SPH (PB)		 PB: L. johnsonii La1 (109 CFUs/d) in yoghurts for 4 wk

  • -Reduce endotoxin concentration in plasma of SNH (a trend in SPH)

  • -Reduce soluble CD14 in SPH

  • -Decrease basal phagocytic activity of monocytes and neutrophil in both SNH and SPH

  • -Upon LPS stiumulation, monocytes from SPH produced less IL-1β and IL-10 than those prior to supplementation, but PB supplementation increased the capacity of monocytes similar to SNH and the capacity of neutrophils to release of reactive oxygen species in SPH

 Schiffrin et al. 2009 [269]

(C) control, (P) placebo, (PB) probiotic supplementation, (S) symbiotic supplementation, SNH: subjects with negative hydrogen breath test, SPH: subjects with positive hydrogen breath test