Table 1.
Gut microbial stimuli that interact with intestinal epithelial cells (IECs)
| IEC sensor/signalling pathway | Microbial stimuli | Microbial species used | In vivo/in vitro and study details | IEC response | References |
|---|---|---|---|---|---|
| Toll‐like receptor 9, nuclear factor‐κB | Unmethylated CpG bacterial DNA1 | Citrobacter rodentium (DBS100), Salmonella typhimurium (ATCC 14028), Helicobacter pylori (PMSS1) | In vivo, Tlr9 −/− mice | Decreases intestinal inflammation and damage following bacterial challenge | 140, 141, 142, 143 1 |
| Caspase‐3/7‐mediated apoptosis | Enterotoxins (TcdA and TcdB) | Clostridium difficile (VPI10463) | In vivo and in vitro intestinal organoids; Casp3/7 IEC‐KO mice | Restricts C. difficile growth in vivo | 144 |
| NAIP/NLRC4 inflammasome |
Flagellin1
Unknown2 |
Salmonella Typhimurium, Citrobacter rodentium 2 | In vivo, Casp1 −/−, Casp8 −/−, Nlrc4 −/− | Protects against enteric pathogen invasion; expulsion of pyroptotic IECs and release of eicosanoid and interleukin‐18 (IL‐18) | 21, 22, 145 1 |
| Toll‐like receptor 4, peroxisome proliferator‐activated receptor (PPAR) | Free fatty acids1 | Commensal gut microbes | In vivo, Tlr4 IEC‐KO | Prevents development of metabolic syndrome; regulates expression of lysozyme and PPAR‐controlled genes | 58, 146, 147, 1 |
| P2X7R/NLRP3 inflammasome | Ligands include extracellular ATP and K+ 1 | Toxoplasma gondii | In vitro, FHs 74 Int cells | IL‐1β secretion and inhibition of parasitic proliferation | 18, 148, 149, 1 |
| NLRP6 inflammasome | Unknown | Citrobacter rodentium | In vivo, Nlrp6 −/−, Asc −/−, Casp1/11 −/− | Orchestrates goblet cell mucin granule exocytosis | 19 |
| Nlrp9b inflammasome | dsRNA1 | Rotavirus EW | In vivo, Nlrp9b −/−, Nlrp9b IEC‐KO | Restricts rotavirus infection by IL‐18 production and pyroptosis | 20 |
| Aryl hydrocarbon receptor | Tryptophan indole derivatives | Lactobacilli, Clostridiales members | In vivo, Ahr −/− | IL‐22 production; resistance to enteric pathogens; maintenance of intestinal homeostasis and barrier functions | 25, 26, 27 |
| Receptors GPR41, GPR43 and GPR109; HDAC inhibition; mTOR, STAT3, ERK and MAPK signalling | short‐chain fatty acids | Various microbes including Bacteroides spp. | In vivo, GPR41 −/−, GPR43 −/−, GPR109 −/−, in vitro murine intestinal organoids | Protective inflammatory responses during pathogen infection; secretion of AMPs, chemokines and cytokines; controls IEC turnover and barrier functions; RALDH1 expression and vitamin A metabolism | 28, 29, 30, 31, 33, 150, 151, 152 |
| MyD88 signalling | Various TLR ligands | Citrobacter rodentium | In vivo, MyD88 −/− | Secretion of AMPs, control of bacterial infiltration, enhanced barrier integrity | 12 |
| GPCR and ERK/MAPK signalling | Pili, novel 3000 MW molecule | Lactobacillus rhamnosus (CNCM I‐3690), Ruminococcus gnavus (E1) | In vivo, in vitro HT29‐MTX cells | Expression of glycoroteins and mucus production by goblet cells; cytoprotective responses | 14, 15 |
| Various cellular stresses including nutrient deprivation, infection with microbes1 | Autophagy | Helicobacter hepaticus, Salmonella Typhimurium, Pasteurellaceae family | In vivo, Atg161 −/− , in vitro Atg161 −/− organoids | Control inflammation‐induced apoptosis, necroptosis and maintains intestinal barrier, lysozyme secretion by Paneth cells, promotes bacterial clearance | 23, 43, 45, 153, 154, 155 1 |
| Cellular forces | Mechanosensors/mechanotransducer Piezo2 | Clostridial species | In vivo, in vitro | Serotonin release by enterochromaffin cells | 35, 37 |
| Peptidoglycan components; muramyl dipeptide1 | Nod2 | Bacteroides vulgatus, Enterococcus faecium | In vivo, Nod2 −/− and in vitro | Restriction of bacterial growth or dissemination, expression of inflammatory genes, goblet cell function | 56, 156, 157, 1, 158 |
| Pregnane X receptor (PXR) | Indole 3‐propionic acid | Clostridium sporogenes | In vivo, Nr1i2 −/−, Nr1i2 −/−, Tlr4 −/−, Pxr −/− | Regulation of intestinal permeability and intestinal inflammation, defence against intracellular pathogens | 24, 159 |
1A finding from a different or additional study.
2While type 3 secretion system components expressed by C. rodentium are thought to provide the stimulus triggering NLRC4 inflammasome formation in vivo, this has yet to be demonstrated.