Table 1.

Studies reporting host-microorganism interactions using human intestinal organoids

Microorganism	Tissue tropism	Systems used	Infection method	Effects	References
Nonpathogenic E. coli	Large intestine	Human ESC	3D-Microinjection	↑Epithelial proliferation ↑Maturation of enterocytes ↑Secretion of antimicrobial peptide ↑Expression of epithelial Mucins and glycotransferases	(47, 61)
Enterohemorrhagic E. coli (EHEC)	Large intestine	Human ESC	3D-Microinjection	↑Inflammatory immune responses ↑ROS production ↑Gastrointestinal maturation ↓Barrier function ↓Mucin layer Microvillar damage	(54, 61)
		Human colon*	2D-Monolayer transwell
Enterotoxigenic E. coli (ETEC)	Small intestine	Human duodenum*, jejunum* and proximal colon	2D-Monolayer transwell	Attached on the apical side ↑Adherence of macrophages	(65)
Shigella flexneri	Large intestine	Human duodenum, ileum, cecum* and colon*	2D-Monolayer transwell	Preference of basolateral invasion ↑Proinflammatory signals ↑Amino acid transporter SLC7A5 ↑Muc2 production ↑Apical invasion by M-cell	(67, 68)
Salmonella enterica serovar Typhimurium	Small intestine (ileum)	Human iPSC*	3D-Microinjection	Invade the epithelial barriers ↑Expression of genes associated with infection and inflammation ↑M cell differentiation Preference of apical surfaces invasion via cytoskeletal rearrangements	(51, 70, 71)
		Human small intestine*	2D-Monolayer
		Human ileum*	2D-Suspension culture
Salmonella enterica serovar Typhi	Large intestine (cecum)	Human ileum	2D-Monolayer transwell	↑Microvilli destruction ↑Cytoskeleton rearrangement ↑Internalization into vesicles	(73)
Vibrio cholerae	Small intestine	Human duodenum* and rectum	3D-Enteroids treated with cholerae toxin	↓NHE3 activity ↑Enteroid swelling CT increases higher cAMP levels in O-blood group than the A-blood group Galactose-fucose copolymer partially blocks intoxication	(78-81)
		Human ileum* and colon	2D-Monolayer transwell
		Human jejunum*
Clostridium difficile	Large intestine	Human ESC	3D-Microinjection	↓Epithelial paracellular barrier function TcdA causes more disruption of cytoskeletal rearrangement than TcdB. ↓Muc2 production Bacitracin reduces the TcdB-induced destruction of F-actin and glucosylation of Rac1	(45, 49, 84, 85)
		Human jejunum	2D-Monolayer transwell
		Human iPSC	3D-Microinjection
		3D-Organoids treated with toxin
Norovirus	Small intestine	Human ESC	2D-Monolayer	Inactivation of norovirus replication by alcohol and chlorine Bile is required for strain-dependent norovirus replication and enhances infectivity	(89, 90)
		Human jejunum*	2D-Monolayer transwell
Rotavirus	Small intestine	Human colon Human jejunum* and ileum*	3D-Organoid treated with rotavirus	Infectious rotavirus particles production Robust viral replication Replication is inhibited by interferon-alpha and ribavirin Preferentially infects differentiated enterocytes and enteroendocrine cells ↑Organoid swelling	(92, 93)
Lactobacillus rhamnosus Lactobacillus reuteri Lactobacillus plantarum	Small intestine	Human small intestine* and colon	3D-Microinjection	↑Epithelial barrier function ↑Mucosal barrier integrity of mature human intestinal organoids than immature human intestinal organoids Survive and colonize on the apical side of the human intestinal organoids	(99, 101)
		Human ESC
Bifidobacterium adolescentis	Large intestine	Human colon*	2D-iHACS AOI chip	↑Differentiation of goblet cell and stem cell Co-cultured with epithelial cells in the AOI Chip for up to a week	(55, 102)
		Human intestinal epithelial Caco-2BBE cells*
Akkermansia muciniphila	Large intestine	Human colon*	2D-iHACS	Only differentiated human colonic organoids can support the growth of A. muciniphila	(55)
Eubacterium	Large intestine	Human intestinal epithelial Caco-2BBE cells*	AOI chip	Co-cultured with epithelial cells in the AOI Chip for up to a week	(102)

ESC: Embryonic stem cells, iPSC: induced pluripotent stem cells, iHACS: intestinal hemi-anaerobic coculture system, AOI chip: Anoxic-Oxic Interface-on-a-Chip. *Matched with tissue tropism.