TABLE 1.
Human organoids models that mimic intestinal diseases mediated by microbial infection and the mechanism analysis.
| Microorganisms/metabolites | Organoids model type | Effects | Mechanisms | Diseases | References |
|---|---|---|---|---|---|
| Yptb | Human ileal enteroid | Yptb type three secretion system causes M cell extrusion from ileal monolayers, Yops impede M cell function | YopE affected the Rac1‐GAP activity | Intestinal infection | 75 |
| Clostridium difficile toxin A and toxin B | Human colonic organoids | Cell rounding | Disruption or reorganization of the cytoskeletal structure | Gastrointestinal infections, diarrhea, and enteritis | 78 , 79 |
| Enterococcus faecalis (Epxs) | Human and mouse organoids | Induce death and damages of human peripheral blood mononuclear cells and intestinal organoids in a toxin‐dependent manner | IFN‐g sensitize intestinal organoids to Epx2 and Epx3, immune suppression and epithelial barrier disruption | Multidrug resistant infections or infections with high mortality or alcoholic liver disease | 98 |
| Pks + E. coli | Human intestinal organoids | DNA damage, ID‐pks/ SBS‐pks signatures pinpointing bacterial “fingerprints” in DNA alterations found in CRC cells, alters in copy number variations and other mutations | DNA alkylation and the induction of double‐strand breaks | CRC | 107 , 108 |
| Improper repair of colibactin‐induced cross‐links | |||||
| Clostridium bolteae (AHG0001 strain) | CD and UC patients‐derived organoids; | Suppress inflammatory responses and endoplasmic reticulum stress | Suppress both cytokine and LPS‐driven chemokine/cytokine expression | IBD | 110 |
| Winnie mice organoids | Suppress NF‐κB activation | ||||
| Lactobacillus species and metabolites 1,3‐diaminopropane | Human intestinal organoids (generated from human pluripotent stem cells) | Sense intestinal iron levels and attenuate host iron absorption | Repress intestinal iron absorptive pathways via the inhibition of basal HIF‐2α function and promote cellular iron storage via the induction of ferritin expression | Iron‐related disorders | 122 |
| Helicobacter pylori | Human gastroids | Aberrantly alter a cancer‐associated tight junction protein | Alter the localization and expression of claudin‐7 in epithelial cells mediated by β‐catenin and snail activation | Gastric adenocarcinoma | 145 |
| Fusobacterium nucleatum (>50 kDa outer membrane vesicles) | Human colonoid monolayer | Stimulate secretion of the proinflammatory cytokines IL‐8 and TNF | Stimulate p‐ERK, p‐CREB, and NF‐κB activation | Intestinal inflammation and CRC | 148 |
| Concentrations of microbiota of UC patients | Human organoid (derived from UC patients and non‐IBD controls) | Dose‐dependent response of inflammatory markers and alterations in transepithelial electrical resistance measurements | Induce transcriptomic stress pathways including activation of EGR1, MAPK and JAK/STAT signaling, as well as AP‐1 family and FOSL transcripts | UC | 150 |
| Fecal supernatant or LPS (IBS patients or Gram‐negative bacteria) | Human colonoids and mouse colonoids | Distinct colonic epithelial gene expression | Activate mast cells to release PGE2 through the induction of the COX‐2 enzyme and to downregulate SERT expression | IBS | 151 , 152 , 153 |
| Increased mucosal 5‐HT | Activite TLR4‐MyD88 signaling pathway | ||||
| Downregulated Lox5 mRNA expression and synthesis of RvD1 | |||||
| SARS‐CoV‐2 | Human intestinal organoids | Induce stronger IFN response | SARS‐CoV‐2 infects enterocyte lineage cells with high ACE2 expression | Intestinal inflammation and damage | 156 |
| HRV | Human intestinal enteroid | Simulate human intestinal physiology and pathophysiology and epithelial response after HRV infection | Support robust replication of HRV G3P[8] and G1[P8] | HRV‐related diarrhea | 159 |
| Clostridium difficile (Clostridium difficile TcdB) | Human and mouse enteroids pluripotent stem cell‐derived human intestinal organoids | Circadian rhythms and circadian phase‐dependent necrotic cell death | Disruption of Rac1 abolished clock‐dependent necrotic cell death | Rhythm‐related diseases | 166 |
| Bifidobacterium longum | Primary cultured enteroids | Promote the proliferation of organoids | Upregulation of the stem niche factors WNT3A and TGF‐β | IBS | 168 |
| A. muciniphila BAA‐835 | Human and mouse organoids | Significantly larger organoids | Promote ISC proliferation in a Wnt3‐dependent manner | Radiation and chemotherapy gut damage | 169 |
| Lactobacillus paracasei | Human intestinal organoids (derivate from CD patients) | Prevent the inflammatory effects | Decrease NFkβ phosphorylation | CD | 170 |
Abbreviations: Yptb, Yersinia pseudotuberculosis; GAP, GTPase‐activating protein; Epxs, enterococcus pore‐forming toxins; E. coli, Escherichia coli; ID‐pks, indel signature induced by Pks + E. coli; SBS‐pks, pks‐specific single base substitution signature; CRC, colorectal cancer; CD, Crohn's disease; UC, ulcerative colitis; LPS, lipopolysaccharide; IBD, inflammatory bowel disease; IL, interleukin; TNF, tumor necrosis factor; ERK, extracellular signal‐regulated kinase; AP‐1: activator protein‐1; IBS, irritable bowel syndrome; PGE2, prostaglandin E2; SERT, serotonin reuptake transporter; SARS‐CoV‐2, severe acute respiratory syndrome–coronavirus 2; IFN, interferon; ACE2, angiotensin converting enzyme 2; HRV, human rotavirus; ISC, intestinal stem cells; NFkβ, nuclear transcription factor‐B.