TABLE 1.
Biological effects of EVs released by species that comprise probiotic strains.
| Genus and species | Strain | Current evidence | Pathogen inhibition | Barrier function | Immune system | Composition | Transport | Other biological effects | References |
| Escherichia coli | Nissle 1917 | EVs improved epithelial barrier function in intestinal epithelial cells (T-84 and Caco-2) | • | Alvarez et al., 2016 | |||||
| Escherichia coli | Nissle 1917 | EVs protected barrier function in human intestinal epithelial cells (T-84 and Caco-2) infected with E. coli (EPEC) | • | Alvarez et al., 2019* | |||||
| Escherichia coli | Nissle 1917 | EVs were endocytosed in a clathrin-dependent manner by human intestinal epithelial cells (HT-29) | • | Cañas et al., 2016 | |||||
| Escherichia coli | Nissle 1917 | EVs incubation with human intestinal epithelial cells (Caco-2) activated NOD1-signaling cascades and NF-κB, and increased IL-6 and IL-8 levels | • | Cañas et al., 2018 | |||||
| Escherichia coli | Nissle 1917 | EVs increased TNF-α, IL-6, IL-8, IL-10 and MIP1α levels in PBMC, human intestinal epithelial cells (Caco-2)/PMBCs co-culture and ex vivo colonic mucosa explants | • | • | • | Fábrega et al., 2016 | |||
| Escherichia coli | Nissle 1917 | EVs improved clinical symptoms and histological scores, protected intestinal epithelial barrier function, and mediated anti-inflammatory effects in a dextran sulfate sodium-induced colitis mouse model | • | • | Fábrega et al., 2017 | ||||
| Escherichia coli | Nissle 1917 | EVs incubation with mouse macrophage cells (RAW264.7) increased TNF-α, IL-4, IL-6, IL-10 and IL-12 levels, and stimulated bacteria-killing ability against E. coli, S. typhimurium, and S. aureus | • | Hu et al., 2020* | |||||
| Escherichia coli | Nissle 1917 | Vaccination with engineered EVs (modified bacteria that express the enterotoxin ClyA) had a strong adjuvant capability on the immune response in mice | • | Rosenthal et al., 2014 | |||||
| Bacillus subtilis | 168 | EVs were transported across human intestinal epithelial cells (Caco-2) | • | Domínguez Rubio et al., 2020 | |||||
| Bifidobacterium bifidum | LMG13195 | EVs incubation with human dendritic cells induced Treg differentiation and increased IL-10 levels | • | López et al., 2012 | |||||
| Bifidobacterium longum | NCC2705 | EVs contained several mucin-adhesion proteins | • | Morishita et al., 2021 | |||||
| Bifidobacterium longum | – | EVs incubation with mouse macrophage cells (RAW264.7) and dendritic cells (DC2.4) increased TNF-α and IL-6 levels | • | • | • | Morishita et al., 2021 | |||
| Clostridium butyricum | – | EVs incubation with mouse macrophage cells (RAW264.7) and dendritic cells (DC2.4) increased TNF-α and IL-6 levels | • | • | • | Morishita et al., 2021 | |||
| Lacticaseibacillus casei | ATCC 393 | EVs contain the protein p75 associated with probiotic effects | • | Dean et al., 2019 | |||||
| Lacticaseibacillus casei | ATCC 393 | EVs incubation with human intestinal epithelial cells (Caco-2) decreased TLR9 gene expression and IFN-γ levels, and increased IL-4 and IL-10 levels | • | Vargoorani et al., 2020 | |||||
| Lacticaseibacillus casei | BL23 | EVs contain proteins p40 and p75 associated with probiotic effects | • | Domínguez Rubio et al., 2017 | |||||
| Lacticaseibacillus casei | BL23 | EVs increased NF-κB levels and induced phosphorylation of epidermal growth factor receptor (EGFR) in human intestinal epithelial cells (HT-29 and T-84, respectively) | • | • | Bäuerl et al., 2020 | ||||
| Lacticaseibacillus paracasei | – | EVs decreased NF-κB levels and mRNA levels of TNFα, IL-1α, IL-1β and IL-2, and increased mRNA levels of TGFβ and IL-10 in LPS-induced inflammation in human intestinal epithelial cells (HT-29) and reduce inflammation symptoms of dextran sulfate sodium-induced colitis in mice. | • | Choi et al., 2020 | |||||
| Lactiplantibacillus plantarum | APsulloc 331261 | EVs increased IL-10, IL-1β and GM-CSF levels in ex vivo human skin cultures, and induced monocyte-to-macrophage transition and polarization to M2b in human monocytic cells (THP-1) | • | Kim et al., 2020 | |||||
| Lactiplantibacillus plantarum | BGAN8 | EVs were endocytosed in a clathrin-dependent manner by human intestinal epithelial cells (HT29) | • | • | Bajic et al., 2020 | ||||
| Lactiplantibacillus plantarum | KCTC 11401BP | EVs decreased IL-6 levels and protected cell viability against treatment with S. aureus EVs in human epidermal keratinocytes (HaCaT), and reduced skin inflammation in S. aureus EV-induced atopic dermatitis in mice | • | Kim et al., 2018* | |||||
| Lactiplantibacillus plantarum | KCTC 11401BP | EVs increased Brain Derived Neurotrophic Factor (BDNF) levels in mouse hippocampal neurons (HT22) and produced antidepressant-like effects in mice with chronic restraint stress | • | Choi et al., 2019 | |||||
| Lactiplantibacillus plantarum | WCFS1 | EVs prolonged the survival of C. elegans infected with vancomycin-resistant enterococci | • | • | Li et al., 2017* | ||||
| Lactiplantibacillus plantarum | WCFS1 | EVs incubation with mouse macrophage cells (RAW264.7) and dendritic cells (DC2.4) increased TNF-α and IL-6 levels | • | • | • | Morishita et al., 2021 | |||
| Lacticaseibacillus rhamnosus | GG | EVs decreased TNF-α, IL-1β, IL-6 and MCP-1 levels in LPS-induced inflammation in mouse macrophage cells (RAW264.7), increased IL-22 levels and decreased hepatic bacterial translocation by reinforcing the intestinal barrier function in alcohol-associated liver disease in mice | • | • | • | Gu et al., 2021 | |||
| Lacticaseibacillus rhamnosus | GG | EVs increased apoptosis in human hepatic cells (hepG2) | • | Behzadi et al., 2017 | |||||
| Lacticaseibacillus rhamnosus | GG | EVs decreased IFN-γ and IL-17A levels in S. aureus-stimulated human PBMC | • | Mata Forsberg et al., 2019* | |||||
| Lacticaseibacillus rhamnosus | GG | EVs inhibited TLR4-NF-κB-NLRP3 axis activation in colonic tissues, and decreased TNF-α, IL-1β, IL-2 and IL-6 levels in dextran sulfate sodium-colitis in mice | • | Tong et al., 2021 | |||||
| Lacticaseibacillus rhamnosus | JB-1 | EVs increased IL-10 and HO-1 levels via Dectin-1, SIGNR1, TLR-2 and TLR-9 activation in dendritic cells, and increased Treg cells in Peyer’s patch from mice | • | Al-Nedawi et al., 2015 | |||||
| Lacticaseibacillus rhamnosus | JB-1 | EVs appeared in blood 2.5 h after oral consumption and contained bacteriophage DNA | • | • | • | Champagne-Jorgensen et al., 2021a | |||
| Lacticaseibacillus rhamnosus | JB-1 | EVs were endocytosed in a likely clathrin-dependent manner by mouse (MODE-K) and human intestinal epithelial cells (HT-29) and by mouse intestinal epithelial cells in vivo. They expose lipoteichoic acid that activated TLR2 and increased IL-10 levels | • | • | • | Champagne-Jorgensen et al., 2021b | |||
| Lactobacillus acidophilus | ATCC 53544 | EVs contain bacteriocins | • | • | Dean et al., 2019 | ||||
| Lactobacillus acidophilus | ATCC 53544 | Bacteriocin-enriched EVs fused with other bacteria | • | • | Dean et al., 2020 | ||||
| Lactobacillus crispatus | BC3 | EVs protected human cervico-vaginal and tonsillar tissues, and human CD4+ T cell lines (MT-4 and Jurkat-tat) from HIV-1 infection by decreasing viral attachment | • | • | Ñahui Palomino et al., 2019* | ||||
| Lactobacillus gasseri | BC12 | EVs protected human cervico-vaginal and tonsillar tissues, and human CD4+ T cell lines (MT-4 and Jurkat-tat) from HIV-1 infection by decreasing viral attachment | • | • | Ñahui Palomino et al., 2019* | ||||
| Lactobacillus gasseri | JCM 1131 | EVs expose lipoteichoic acid on the surface during logarithmic phase | • | Shiraishi et al., 2018 | |||||
| Lactobacillus johnsonii | N6.2 | EV expose proteins that are recognized by IgA and IgG from plasma of individuals who had consumed the probiotic | • | Harrison et al., 2021 | |||||
| Latilactobacillus sakei | NBRC15893 | EVs promoted IgA production by murine Peyer’s patch cells via TLR2 | • | Yamasaki-Yashiki et al., 2019 | |||||
| Limosilactobacillus reuteri | ATCC 23272 | EVs contain no bacteriocins, even though this strain produces high levels of these antibacterial molecules | • | Dean et al., 2019 | |||||
| Limosilactobacillus reuteri | BBC3 | EVs decreased mRNA levels of TNF-α, IL-1β, IL-6, IL-17 and IL-8, and increased mRNA levels of IL-10 and TGF-β in LPS-induced inflammation in chicken | • | • | Hu et al., 2021 | ||||
| Limosilactobacillus reuteri | DSM 17938 | EVs decreased IFN-γ and IL-17A levels in S. aureus-stimulated human PBMC | • | Mata Forsberg et al., 2019* | |||||
| Limosilactobacillus reuteri | DSM 17938 | EVs mimicked the effect of the bacteria on gut motility in mice | • | West et al., 2020 | |||||
| Propionibacterium freudenreichii | CIRM-BIA 129 | EVs decreased NF-κB and IL-8 levels in LPS-induced inflammation in human intestinal epithelial cells (HT-29) | • | • | Rodovalho et al., 2020 |
EVs that have had beneficial effect against pathogens in in vitro, ex vivo, or in vivo models are indicated by asterisks.