Table 3.

Studies evaluating the role of microbiota derived BEVs as modulators of intestinal homeostasis-related processes

Bacteria	Mechanism	Experimental approach	References
Gut ecology and food metabolism
Bacteriodes fragilis  B. thetaiotaomicron	Metabolism of complex carbohydrates to produce SFCAs: Expression of glycosyl-hydrolases, sulfatases, proteases Cholesterol uptake: upregulation NPC1L1 receptor Metabolites in BEVs that facilitate intestinal colonization	Proteomics of BEVs by mass spectrometry In vitro Caco-2 cell culture In silico, proteomic and metabolomic analysis	[137, 188, 206–208]
B. thetaiotaomicron	Assimilation of dietary Insitol-P Macrophage internalization (Sulfatases)	Biochemical characterization of InsP6-phosphatase Experimental model of colitis using genetically modified mice	[209, 210]
Bacteroides fragilis	Antibiotic resistance (β-lactamases)	Knockout mutant of putative β-lactamase gene	[150]
Epithelial barrier integrity
E. coli Nissle 1917  ECOR63 strain	Upregulation of TJ proteins ZO-1 and claudin-14, downregulation of claudin-2 Protection against EPEC-induced damage: preservation of occludin and claudin-14 mRNA levels, redistribution of ZO1, amelioration of F-actin disorganization	In vitro Caco-2 and T-84 cell cultures: RT-qPCR, confocal microscopy In vitro Caco-2 and T-84 cell cultures infected with EPEC: RT-qPCR, confocal microscopy, paracellular permeability assays	[116, 211]
E. coli Nissle 1917	Upregulation TFF3 and MMP-9 mRNA	In vivo mice model of DSS-induced colitis	[117]
Akkermansia muciniphila	Upregulation of ZO-1, claudin 5 Upregulation of ZO-1, ccluding, claudin-1 Upregulation of ccluding, ZO-1/2, claudin-4	In vivo high-fat diet (HFD)-induced diabetic mice model, and Caco-2 cell culture In vivo HFD-induced obesity mice model In vitro Caco-2 cells challenged with LPS	[212–214]
Gut immunity: modulation of inflammatory responses through the intestinal epithelium
E. coli Nissle 1917  ECOR12 strain	Upregulation of IL-6, IL-8, TNF-α, IL-10, MIP1α Upregulation of IL-22 and β-defensin Downregulation of IL-12 Activation of NOD-1 / NF-κB pathway	In vitro Caco-2/PBMCs cell coculture model Ex vivo model of colonic explants Caco-2 cells: NOD1 silencing—RIP2 kinase inhibition	[215, 216]
E. coli Nissle 1917	Upregulation of IL-10; downregulation of IL-1β, TNF-α, IL-6, IL-12, IL-17, iNOS and COX-2 in colonic tissue	In vivo mice model of DSS-induced colitis	[117]
Lactobacillus kefir  L. kefiranofaciens  L. kefirgranum	Downregulation of IL-8 Counteract oxidative stress by decreasing myeloperoxidase serum levels	Caco-2 cells challenged with TNF-α In vivo mice model of TNBS-induced IBD	[217]
Gut immunity: modulation of DCs and derived T cell responses
Bacteroides fragilis	Induction Treg cells (CD4 + CD25 + FOXP3 +) and IL-10 production through a mechanism that involves TLR2 Activation of autophagy. Induction of Treg cells and IL-10 production depends on functional ATG16L1 and NOD2	In vivo mice model of TNBs-induced colitis In vitro bone marrow-derived DCs culture BEVs from wild-type and PSA deficient strains Bone-marrow derived DCs from wild type, ATG16L1- and NOD2 deficient mice In vitro cocultures of BMDCs with CD4+T cells In vivo mice model DNBS-induced colitis	[94, 96]
Bacteroides vulgatus mpk	Induction of DC tolerance via TLR2 and TLR4 Upregulation of co-stimulatory molecules including MHC-II, CD40, CD80 and CD86 in CD11c+ cells	In vitro bone marrow-derived DCs culture TLR4/TLR2 knockout mice model	[218]
Lactobacillus rhamnosus JB-1	Increased production of IL-10 and regulatory (CD4+CD25+FOXP3+) T cells	In vitro bone marrow-derived DCs culture In vivo mice model	[219]
Lactobacillus sakei	Enhance IgA expression	Ex vivo model of murine Peyer's patches	[220]
Bifidobacterium bifidum LMG13195	Promote differentiation to regulatory T cells (CD4+CD25+FOXP3+) and IL-10 secretion	In vitro model of monocyte-derived DCs co-cultivated with CD4+ T cells	[221]
Bifidobacterium longum	Apoptosis of bone-marrow-derived mast cells through ESBP vesicular protein	In vivo mouse model of allergen-induced food allergy	[222]
E. coli Nissle 1917  Commensal E. coli	Upregulation of driver Th cytokines by DCs in a strain-specific manner Differential induction of Th1, Th2, Th17/Th22 and T regulatory responses Regulation of key miRNAs in immunity (miR-155, miR-146a/b and miR-let7i) Differential modulation of miRNAs involved in tolerogenic responses (miR-125a/99b/let7e, miR-125b, miR-24)	In vitro model of monocyte-derived DCs co-cultivated with CD4+ T cells In vitro model of monocyte-derived DCs: RNA seq approaches to identify differential expressed miRNAs	[223, 224]