Table 1.
Invasive and noninvasive enteric bacteria that have been studied using human organoids and enteroids and the respective research focus. *Enteroid – no mesenchyme; from duodenum, jejunum, or ileum. **Colonoid – no mesenchyme; from colon or cecum. ***HIO: human induced pluripotent stem cell derived-intestinal organoid (epithelium and mesenchyme).
Bacteria | Origin | Intestinal section | Type | Research focus | Refs |
---|---|---|---|---|---|
Invasive pathogens | |||||
Shigella flexneri | Human Biopsy | Duodenum, Ileum, Colon | 2D Enteroid*, 2D Colonoid** | Invasion, intracellular replication, host gene expression | 21 |
Human Biopsy | Duodenum, Jejunum, Ileum, Colon | 2D Enteroid, 2D Colonoid | Invasion, M cells, intracellular replication, mucus changes, cytokine secretion | 22 | |
Human Biopsy | Cecum | 2D Colonoid | Testing bacteriophage therapy | 23 | |
Human Biopsy | Colon | 2D Colonoid | Adherence factor expression | 24 | |
Listeria monocytogenes | Human Biopsy | Ileum | 3D Enteroid | Reversing enteroid polarity to facilitate apical infection | 25 |
Salmonella enterica serovar Typhimurium | iPSC (dermal fibroblasts) | n/a | 3D HIO*** | Invasion, infection-associated transcriptional changes | 26 |
iPSC | n/a | 3D HIO | Organoids derived from healthy iPSC and infant IBD patient; role of IL-22 in controlling infection | 27 | |
Human Biopsy | Ileum | 3D Enteroid | Reversing enteroid polarity to facilitate apical infection | 25 | |
Salmonella enterica serovar Typhi | Human Biopsy | Ileum | 2D Enteroid | Cytoskeletal changes during infection | 28 |
Noninvasive pathogens | |||||
Enterotoxigenic E. coli | Human biopsy | Duodenum, jejunum | 3D Enteroid | Toxin-mediated inhibition of ion transporter NHE3 | 29 |
Human biopsy | Jejunum | 2D Enteroid | Toxin-induced polarized cyclic nucleotide secretion | 30 | |
Human biopsy | Jejunum | 2D Enteroid | ST-induced pathology in Intestine Chip model | 31 | |
Human biopsy | Jejunum, ileum | 2D Enteroid | Minor adhesin-mediated adherence & cyclic nucleotide production | 32 | |
Human biopsy | Duodenum, jejunum, colon | 2D Enteroid, 2D Colonoid | Effect of macrophage co-culture on infection and epithelial cell differentiation | 33 | |
Enterohemorrhagic E. coli | Human biopsy | Colon | 2D Colonoid | Role of mucus and SPATE EspP in infection | 34 |
Human biopsy | Colon | 2D Colonoid | SPATE EspP-induced ion transport | 35 | |
iPSC | n/a | 3D HIO | Pathogen vs. commensal effect on epithelium; co-culture with neutrophils | 36 | |
iPSC | n/a | 3D HIO | Shiga toxin effects and mesenchymal-epithelial cross talk | 37 | |
Enteroaggregative E. coli | Human biopsy | Duodenum, ileum, colon | 2D Enteroid, 2D Colonoid | Adherence patterns by donor and intestinal segment type | 38 |
Human biopsy | Colon | 2D Colonoid | SPATE SepA-induced ion transport | 35 | |
Enteropathogenic E. coli | Human biopsy | Duodenum, jejunum, colon | 2D Enteroid, 2D Colonoid | Effect of macrophage co-culture on infection and epithelial cell differentiation | 33 |
Clostridium difficile | iPSC | n/a | 3D HIO | Viable bacterial infection, toxin-induced pathology | 39 |
Human biopsy | Colon | 3D Colonoid | Toxin receptor expression | 40 | |
Human biopsy | Jejunum | 2D Enteroid | Toxin-induced pathology, toxin receptor expression | 41 | |
Human biopsy | Colon | 3D Colonoid | Toxin binding to intestinal receptors | 42 | |
iPSC | n/a | 3D HIO | Role of mucus in infection | 43 | |
iPSC | n/a | 3D HIO | Dysregulation of ion transporter NHE3 and microbiota | 44 | |
iPSC | n/a | 3D HIO | Human alpha-defensin-1 and toxin neutralization | 45 | |
iPSC | n/a | 3D HIO | Bacitracin as defense against toxins | 46 | |
Vibrio cholerae | Human biopsy | Duodenum, jejunum | 3D Enteroid | Toxin-mediated inhibition of ion transporter NHE3 | 29 |
Human biopsy | Ileum, colon | 2D Enteroid, 2D Colonoid | Toxin-induced cyclic nucleotide production | 47 | |
Human biopsy | Rectum | 3D Enteroid | Toxin inhibitors to reduce pathology | 48 | |
Human biopsy | Rectum | 3D Enteroid | Toxin inhibitors to reduce pathology | 49 | |
Human biopsy | Jejunum | 2D Enteroid | Toxin inhibitors targeting a non-canonical binding site | 50 | |
Extraintestinal pathogenic E. coli (ExPEC) | Human biopsy | Jejunum | 2D Enteroid | Pilus-mediated adherence & invasion | 51 |
Bacteria causing necrotizing enterocolitis (NEC) | Human biopsy, fetal | Duodenum | 2D & 3D Enteroid | Immune response, maturation, & barrier function in fetal vs. adult intestine | 52 |
Human biopsy, fetal | Ileum | 3D Enteroid | Anti-inflammatory metabolite as probiotic | 53 | |
Human biopsy, fetal | Ileum | 3D Enteroid | Human milk oligosaccharides as probiotic | 54 | |
Human biopsy, fetal | Not specified | 3D Enteroid | Cell stress and apoptosis of intestinal stem cells | 55 | |
Human biopsy, fetal | Ileum | 3D Enteroid | Impaired signaling and its role in dysfunction of intestinal regeneration | 56 |