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Table 3 Studies evaluating the role of microbiota derived BEVs as modulators of intestinal homeostasis-related processes

From: Emerging role of bacterial outer membrane vesicle in gastrointestinal tract

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, 206,207,208]

 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

[212,213,214]

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]