Table 5.
Identified gut microbes regulating intestinal mucosal immunity.
| Microbial species | Involved substances | Involved intermediates | Key description | Refs. |
|---|---|---|---|---|
| Lactobacilli, Clostridiales members | Tryptophan indole derivatives | AhR | IL-22 production; resistance to enteric pathogens; maintenance of intestinal homeostasis and barrier functions | (180–182) |
| Various microbes including Bacteroides spp. | SCFAs | Receptors GPR41, GPR43 and GPR109, HDAC inhibition, mTOR, STAT3, ERK and MAPK signaling | Protective inflammatory responses during pathogen infection; secretion of AMPs, chemokines and cytokines; controls IECs turnover and barrier functions; RALDH1 expression and vitamin A metabolism | (21) |
| Clostridium sporogenes | Indole 3-propionic acid | PXR | Regulation of intestinal permeability and intestinal inflammation, defense against intracellular pathogens | (183) |
| Clostridial species | Mechanosensors/mechanotransducer Piezo2 | Cellular forces | Serotonin release by enterochromaffin cells | (171, 184) |
| Bacteroides vulgatus, Enterococcus faecium | Nod2 | Peptidoglycan components; muramyl dipeptide | Restriction of bacterial growth or dissemination, expression of inflammatory genes, goblet cell function | (185) |
| C. rodentium, S. typhimurium, H. pylori | Unmethylated CpG bacterial DNA | NF-κB, TLR9 | Decreases intestinal inflammation and damage following bacterial challenge | (186) |
| Helicobacter hepaticus, S. typhimurium, Pasteurellaceae family | Autophagy | Cellular stresses | Control inflammation-induced apoptosis, necroptosis and maintains intestinal barrier, lysozyme secretion by Paneth cells, promotes bacterial clearance | (187) |
| Rotavirus EW | dsRNA | Nlrp9b inflammasome | Restricts rotavirus infection by IL-18 production and pyroptosis | (188) |
| Commensal gut microbes | Free fatty acids | TLR4, PPAR | Prevents development of metabolic syndrome; regulates expression of lysozyme and PPAR-controlled genes | (189) |
| C. rodentium | TLR ligands | MyD88 signalling | Secretion of AMPs, control of bacterial infiltration, enhanced barrier integrity | (190) |
| Toxoplasma gondii | ligands include extracellular ATP | P2X7R/NLRP3 inflammasome | IL-1β secretion and inhibition of parasitic proliferation | (191) |
| Lactobacillus rhamnosus, Ruminococcus gnavus | Pili | GPR and ERK/MAPK signaling | Expression of glycoroteins and mucus production by goblet cells; cytoprotective responses | (192) |
| Salmonella Typhimurium, C. rodentium | Flagellin | NAIP/NLRC4 inflammasome | Protects against enteric pathogen invasion; expulsion of pyroptotic IECs and release of eicosanoid and IL-18 | (193) |
| Clostridium difficile | Enterotoxins | Caspase-3/7-mediated apoptosis | Restricts C. difficile growth in vivo | (194) |
AhR, aryl hydrocarbon receptor; SCFAs, short-chain fatty acids; GPR, G protein-coupled receptor; PXR, pregnane X receptor; HDAC, histone deacetylase; RALDH1, aldehyde dehydrogenase 1; Nod2, nucleotidebinding oligomerization domain 2; TLR9, toll-like receptor 9; dsRNA, double-stranded RNA; Nlrp9b, NLR family, pyrin domain containing 9B; PPAR, peroxisome proliferator-activated receptor; P2X7R, P2X7 receptor; IECs, Intestinal epithelial cells.