Patient-derived organoids for therapy personalization in inflammatory bowel diseases

Table 1 Molecular target identified by treatment of intestinal organoids with current therapies for inflammatory bowel disease

Molecular target	Treatment effect	Drug	Species	Ref.
E-cadherin	Re-distribution of protein on intestinal surface restored correct permeability	5-aminosalycilic acid, azathioprine	Mouse (IL-10-/-)	[19]
Desmoglein-2	Restored physiological desmoglein-2 expression levels	5-aminosalycilic acid	Mouse (IL-10-/-)	[19]
UBD	Restored physiological UBD expression levels	Infliximab	Human (UC patients)	[88]
CLDN-2	Restored physiological CLDN-2 expression levels	Prednisolone, tofacitinib	Human (CD and CRC patients)	[89,92]
ZO-1	Re-distribution of protein on intestinal surface restored correct permeability	Tofacitinib	Human (CRC patients)	[92]

CD: Crohn's disease; CLDN-2: Claudin-2; CRC: Colorectal cancer; IL-10: Interleukin-10; UBD: Ubiquitin D; UC: Ulcerative colitis; ZO-1: Zonula occludens.

Table 2 Novel potential molecular targets identified using intestinal organoids

Potential molecular targets	Effect	Species	Ref.
LRH-1	Improved resistance to pro-inflammatory mediators and induced mucosal healing	Humanized mouse (Lrh-1-/- LRH-1+/+) and Human	[94]
PXR	Reduced NF-kB activity	Human (IBD patients)	[97]
IL-22-pSTAT3 SP	Restored tissue damage and intestinal homeostasis	Mouse (ATF3-/-)	[98]
TGF-β SP	Arrested inflammatory signals	Mouse	[104]
SIRT2	Regulated Wnt/β-catenin SP	Mouse (Sirt2–/–)	[105]

ATF3: Activating transcription factor 3; IBD: Inflammatory bowel disease; IL: Interleukin; LRH-1: Liver receptor homolog 1; NF-kB: Nuclear factor-kappa B; PXR: Pregnane X receptor; SIRT2: Human sirtuin protein 2; SP: Signaling pathway; STAT: Signal transducer and activator of transcription; TGF-β: Transforming growth factor Β.

Table 3 Potential therapeutic approaches for inflammatory bowel disease treatment identified using intestinal organoids

Potential therapeutic approaches	Effect	Species	Ref.
Sex hormones	Decreased expression of ER stress markers	Human (UC female patients)	[100]
Naltrexone	Reduced ER stress levels, increased the expression of endogenous encephalins and endorphins	Human (IBD patients)	[101]
Bacillus subtilis (RZ001)	Promoted intestinal mucosa repair	Mouse	[102]
Bacterial indoleacrylic acid	Promoted anti-inflammatory cytokines secretion while inducing goblet cells differentiation	Mouse	[103]
Hyaluronan 35 kDa	Promoted epithelial wound healing	Mouse	[106]

ER: Endoplasmic reticulum; IBD: Inflammatory bowel disease; UC: Ulcerative colitis.