Probiotic intervention has strain-specific anti-inflammatory effects in healthy adults

Table 1 Counts of cells of innate and adaptive immunity (10⁹/L) and levels of immunoglobulins (g/L) in serum and secretory IgA (g/mL) in saliva in healthy adults (n = 62) at baseline presented as median (IQR)

	Placebo (n = 16)	LGG (n = 13)	Bb12 (n = 16)	PJS (n = 17)	P value1
Leukocytes	4.90 (3.90-7.05)	5.20 (4.90-6.40)	5.25 (4.60-6.00)	4.90 (4.35 -5.70)	0.55
Monocytes	5.00 (4.25-6.75)	5.00 (5.00-6.00)	6.00 (5.00-6.00)	6.00 (4.50-6.50)	0.84
Neutrophils	2.05 (1.67-3.72)	3.10 (2.50-3.30)	2.95 (2.12-3.47)	3.10 (2.15-3.45)	0.39
Basophils	0.05 (0.00-0.10)	0.10 (0.00-0.10)	0.05 (0.00-0.10)	0.00 (0.00-0.10)	0.73
Eosinophils	4.00 (3.00-5.75)	3.00 (2.00-6.00)	3.00 (2.25-4.75)	2.00 (1.50-3.00)	0.077
Lymphocytes	38.0 (33.5-48.7)	35.0 (31.5-37.5)	34.0 (30.0-40.5)	31.0 (26.0-40.5)	0.24
IgM	1.28 (0.97-1.65)	0.87 (0.69-1.32)	1.10 (0.73-1.66)	1.44 (0.80-1.77)	0.31
IgG	10.7 (9.5-12.2)	10.3 (9.3-11.7)	10.6 (9.1-12.1)	10.4 (8.4-11.7)	0.72
IgA	2.65 (2.45-3.21)	2.42 (2.04-3.44)	2.20 (1.73-2.94)	2.44 (1.53-2.85)	0.22
sIgA	0.23 (0.15- 0.34)	0.27 (0.14-0.42)	0.40 (0.27-0.88)	0.28 (0.17-0.49)	0.065

¹Kruskall-Wallis test with Monte Carlo P values. IQR: Interquartile range.

Table 2 The effect of a 3-wk probiotic intervention on in vitro cytokine production (pg/mL) in peripheral blood mononuclear cells stimulated with Streptococcus pyogenes, lipopolysaccharide (LPS) from E. coli and Influenza A H3N2 virus of healthy adults (n = 62) presented as median AUC_0-21 minus baseline (IQR)

	Placebo (n = 16)	LGG (n = 13)	Bb12 (n = 16)	PJS (n = 17)	P value1	Localization
TNF-α
Streptococcus	703 (-315-1784)	-1883 (-2389-540)	-645 (-1843-1403)	315 (-1045-1460)	0.025	LGG vs placebo
Influenza	31 (-3-66)	6 (-83-84)	-27 (-101-37)	29 (-39-83)	0.32
LPS	11 (-16-38)	-15 (-31-10)	14 (-36-48)	-6 (-78-36)	0.53
IFN-γ
Streptococcus	-19 (-221-97)	-10 (-227-284)	71 (-161-360)	-23 (-223-155)	0.6
Influenza	117 (29-284)	-72 (-221-194)	-7 (-436-189)	102 (-59-218)	0.25
LPS	NA	NA	NA	NA
IL-1β
Streptococcus	2308 (45-5222)	-1324 (-5609-352)	444 (-6152-5000)	649 (-3412-3747)	0.49
Influenza	166 (13-478)	83 (-183-273)	-15 (-817-170 )	156 (-75-791)	0.69
LPS	67 (-29-138)	5 (-147-114)	51 (-40-122)	17 (-43-199)	0.66
IL-2
Streptococcus	5 (-23-79)	-46 (-176-0)	1 (-135-97)	39 (-105-213)	0.33
Influenza	25 (-18-42)	14 (-51-62)	-55 (-162-14)	10 (-27-39)	< 0.001	Bb12 vs others
LPS	2 (-18-35)	27 (-25-57)	1 (-42-51)	6 (-35-25)	0.54
IL-6
Streptococcus	793 (-691-4829)	-379 (-3955-397)	205 (-2757-1553)	175 (-4344-909)	0.82
Influenza	1530 (166-4632)	1288 (-4329-4073)	550 (-7178-1905)	1644 (-327-3344)	0.74
LPS	947 (-418-2527)	-2189 (-3675-4053)	329 (-1949-3950)	639 (-1217-1607)	0.13
IL-8
Streptococcus	240 (-1585-3914)	34 (-3066-3143)	400 (-3638-2891)	132 (-2667-2976)	0.96
Influenza	-455 (-1966-1670)	-193 (-2953-1520)	-1675 (-4245 to -601)	-1148 (-2550-1707)	0.31
LPS	-742 (-3384-180)	-149 (-1608-1517)	-334 (-2692-739)	-1111 (-2457-836)	0.78
IL-10
Streptococcus	907 (263-2149)	-4 (-881-2420)	452 (-2982-1735)	226 (-86-950)	0.29
Influenza	95 (48-284)	-57 (-159-233)	4 (-301-130)	95 (13-350)	0.25
LPS	381 (19-602)	78 (-298-656)	347 (-403-796)	187 (28-1440)	0.51
IL-12
Streptococcus	26 (-18-75)	-32 (-99-36)	22 (-36-67)	35 (-73-172)	0.46
Influenza	0 (-4-16)	7 (-9-30)	8 (-19-51)	5 (-25-37)	0.88
LPS	15 (1-36)	3 (-7-28)	0 (-6-29)	0 (-62-20)	0.23

¹Median regression analysis. AUC: Area under curve (calculated from baseline, 1, 7 and 21 d minus baseline); IQR: Interquartile range; LGG: Lactobacillus rhamnosus GG; Bb12: Bifidobacterium animalis ssp. lactis Bb12; PJS: Propionibacterium freudenreichii ssp. shermanii JS; NA: Not analyzed.

Table 3 Detection of individual probiotic genomic DNA from fecal samples by quantitative PCR at baseline and after the 3-wk probiotic intervention in healthy adults (n = 62)

Strain	Fecal samples
	Placebo (n = 16)		LGG (n = 13)		Bb12 (n = 16)		PJS (n = 17)
	Baseline	After intervention	Baseline	After intervention	Baseline	After intervention	Baseline	After intervention
L. rhamnosus GG
Number of subjects1	7	10	7	13	10	5	6	9
Mean (SD)2	4.7 (1.2)	5.1 (1.1)	5.1 (1.4)	8.6 (0.6)	5.2 (1.3)	4.6 (1.5)	4.5 (1.2)	5.0 (1.4)
B. animalis ssp. lactis Bb12
Number of subjects1	6	5	5	2	7	16	2	4
Mean (SD)2	5.4 (1.6)	5.3 (1.7)	5.3 (1.4)	4.9 (1.3)	5.4 (1.6)	8.6 (0.5)	4.7 (1.1)	5.1 (1.6)
P. freudenreichii ssp. shermanii JS
Number of subjects1	4	2	2	2	4	4	1	16
Mean (SD)2	4.5 (1.4)	4.0 (0.7)	4.1 (0.8)	4.0 (0.6)	4.4 (1.6)	4.2 (0.9)	3.8 (0.3)	8.3 (1.0)

¹Number of subjects harboring a detectable level of the strain.

²Mean (log₁₀) genome copies/g (SD). Detection limits for LGG and PJS is 3.7 log₁₀ genome copies/g and for Bb12 4.3 log₁₀ genome copies/g.