TABLE 1.
Transcriptomic and proteomic preclinical and clinical studies of the immunomodulatory activities of probiotics1
| Type of study | Treatment | Sample | Omics platform | Molecular mechanisms | Clinical outcome | Reference |
|---|---|---|---|---|---|---|
| Animal study | Lactobacillus rhamnosus CNCM I-3690 (5 × 109 CFU) | Blood, MLN, spleen, colon, and ileum | Transcriptomics (microarrays) | Inhibition of ΝF-κB pathway | ↓Systemic inflammation, restored colon and ileum permeability | Martín et al. (15) |
| DNBS-induced chronic microinflammation (SPF male C57BL/6 mice) (n = 30) | 10-d gavage regimen | |||||
| Animal study | Bifico >1.2 × 107 CFU/d (Bifidobacterium longum, L. acidophilus, Enterococcus faecalis) | Colon | Transcriptomics (microarrays) | ↓Proinflammatory chemokines (Cxcl-1, -2, -3, and -5, Ccl-7) | ↓Tumor formation | Song et al. (16) |
| AOM/DSS C57BL/6J mice (n = 14) | Gavage, daily, 3 cycles of DSS treatments | ↓Colonic inflammation | ||||
| Animal study | B. bifidum PRL2010 (109 CFU) | Colon | Transcriptomics (microarrays) | Upregulation of tight-junction genes and β-defensin, downregulation of immune modulators | Modulation of innate immune responses | Turroni et al. (17) |
| Female BALB/c mice (n = 5) | 5-d oral inoculation | |||||
| Animal study | L. plantarum JDFM LP11 (2.5 × 107 CFU/ml) | Ileum | Transcriptomics (RNA-Seq) | ↓Bpi, ↓Rsad2, | Morphological changes in the epithelial layers of the intestines | Shin et al. (18) |
| Female crossbred piglets (n = 6) | Liquid and solid probiotics via drinking and feeds, daily for 4 wk | ↓Slpi, ↓Lum | ||||
| ↓Olfm4, ↓Dmbt1 | ||||||
| Animal study | Saccharomyces boulardii (108 CFU) | Draining mesenteric lymph nodes | Transcriptomics (RNA-Seq) | Modest transcriptional changes | Induced systemic immune response | Hudson et al. (19) |
| C57BL/6 mice (n = NS) | Gavage the day of analysis (single dose) | |||||
| Animal study | L. paracasei K5 (5 × 108 CFU) | Air pouch exudate | Proteomics (microarrays) | Modulation of chemokine expression | ↑Leukocyte recruitment (induced by all strains) | Chondrou et al. (20) |
| BALB/c mice (air pouch model) (n = 10) | L. casei ATCC 393 (5 × 108 CFU) | |||||
| LGG (5 × 108 CFU) | ||||||
| Subcutaneous injection in air pouch | ||||||
| Animal study | L. pentosus 281 (5 × 108 CFU) | Air pouch exudate | Proteomics (microarrays) | ↑sICAM | ↑Leukocyte recruitment (induced by all strains) | Saxami et al. (21) |
| BALB/c mice (air pouch model) (n = 10) | L. plantarum 282 (5 × 108 CFU) | ↑IL-16 | ||||
| L. casei ATCC 393 (5 × 108 CFU) | ↓CXCL-13 | |||||
| LGG (5 × 108 CFU) | ↓TIMP-1 | |||||
| Subcutaneous injection in air pouch | ↓M-CSF | |||||
| Animal study | L. casei ATCC 393 (109 CFU) | Tumor tissue | Proteomics (microarrays) | Modulation Th1 responses | ↓Mean tumor volume | Aindelis et al. (22) |
| Colon CT26 syngeneic tumor mice model (n = 10) | Oral administration, daily for 13 d | |||||
| Animal study | L. acidophilus (6 × 108 CFU) | Serum and colonic tissue | Proteomics (microarrays) | Elevation of TGF-β | ↓Mean tumor number | Mendes et al. (23) |
| AOM/DSS male C57BL/6 mice (n = 29) | L. rhamnosus (6 × 108 CFU) | |||||
| B. bifidum (6 × 108 CFU) | ||||||
| Oral gavage, daily for 3 cycles of DSS treatments | ||||||
| Randomized placebo-controlled, single-blind crossover study | L. casei Shirota (1.3 × 1010 CFU) | Venous blood, saliva | Proteomics (microarrays) | ↑NK cell activity | Immunomodulation | Dong et al. (24) |
| Healthy volunteers (55–80 y) (n = 16) | Per os, daily for 4 wk followed by a 4-wk washout period and 4 wk crossover to the other treatment | Increased | ||||
| IL-10/IL-12 ratio | ||||||
| Randomized, placebo-controlled, crossover study | L. acidophilus (5.2 × 1010 CFU) | Duodenum tissue | Transcriptomics (microarrays) | Modulation of the IFN and IL signaling | Species- and host-specific immunomodulation | van Baarlen et al. (25) |
| Healthy volunteers (n = 7) | L. casei (3.2 × 1010 CFU) | |||||
| L. rhamnosus (1.68 × 1010 CFU) | ||||||
| Per os, daily for 6 wk | ||||||
| Phase I open-label study | LGG (1010 CFU) | Venous blood | Transcriptomics (RNA-Seq) | Modulation of the expression of immune cell trafficking and inflammatory response gene-sets | Modulation of inflammation | Solano-Aguilar et al. (26) |
| Elderly healthy volunteers (65–80 y) (n = 11) | Per os, 2 capsules daily for 28 d |
1
AOM, azoxymethane; Bpi, bactericidal permeability increasing protein; Ccl, chemokine (C-C motif) ligand; CFU, colony-forming units; Cxcl, chemokine (C-X-C motif) ligand; Dmbt1, deleted in malignant brain tumors 1; DNBS, dinitrobenzene sulfonic acid; DSS, dextran sodium sulfate; LGG, Lactobacillus rhamnosus GG; Lum, lumican; M-CSF, macrophage colony-stimulating factor; MLN, mesenteric lymph node; NS, not specified; Olfm4, olfactomedin 4; Rsad2, radical S-adenosyl methionine domain-containing 2; sICAM, soluble intercellular adhesion molecule; Slpi, secretory leukocyte peptidase inhibitor; SPF, specific pathogen free; Th1, T helper cell type 1; TIMP-1, metallopeptidase inhibitor 1; ↓, statistically significant downregulation; ↑, statistically significant upregulation.