Table 1.

Summary of the known effects of microbial species and strains on ISC regulation.

Microbe / Strain		Model	Effects on ISCs	Mechanisms	Reference
Akkermansia muciniphila
	ATCC BAA-835 and AK32	Normal mouse, radiation and methotrexate mouse damage model	Stimulates proliferation of Lgr5+ ISCs, promotes differentiation to Paneth cells and goblet cells, promotes gut repair following damage	Activates Wnt/β-catenin pathway by promoting Wnt3 secretion	Kim et al. (2021), Duan et al. (2023)
Bacillus subtilis
	JNFE0126	DSS-induced mouse colitis model	Stimulates proliferation, increases Lgr5+ ISC numbers	Protects ISCs from inflammatory injury; rebalances intestinal microbiota	Zhang et al. (2020)
Bacteroides fragilis
	ZY-312	DSS-induced mouse colitis model	Promotes colonic proliferation	Promotes colonic mucosal regeneration in colitis via IL-22-induced STAT3 phosphorylation	Zhang et al. (2023)
	086-5443-2-2	Human colonic epithelial HT29/C1 cells	Promotes proliferation and c-myc expression	Activates β-catenin/TCF signaling pathway via	Wu et al. (2003)
Erwinia carotovora carotovora 15
	Ecc15	Ecc15-infected Drosophila model	Stimulates ISC proliferation and differentiation to enteroendocrine cells	JAK-STAT pathway induction of ISC proliferation via Upd3 release from enterocytes	Buchon et al. (2009b), Liu et al. (2022)
Lactobacillus acidophilus
	ATCC4356	Salmonella typhimurium-infected mouse intestinal organoids	Inhibits proliferation, inhibits excessive differentiation of Paneth cells and goblet cells	Inhibits overactivation of Wnt/β-catenin pathway	Lu et al. (2020)
Lactobacillus casei
	ATCC334	Radiation-induced rat injury model	Stimulates proliferation, increases Lgr5+ ISC numbers	Promotes proliferation via alpha-linolenic acid production and IL-22	Hua et al. (2023)
	ATCC334	Normal mouse and porcine epithelial cells	Stimulates epithelial cell proliferation	Induces epithelial expression of Reg3a to inhibit pathogens and stimulate damage repair	Bai et al. (2021)
Lactobacillus plantarum
		Normal Drosophila	Stimulates ISC proliferation	Nox1-dependant reactive oxygen species generation	Jones et al. (2013)
Lactobacillus reuteri
	D8	C. rodentium-infected mouse, DSS-induced mouse colitis model, TNF-damaged mouse organoids	Stimulates proliferation, induces differentiation of Paneth cells, increases Lgr5+ ISC numbers	Induces R-spondin expression and activates Wnt/β-catenin pathway;	Wu et al. (2020)
	D8			Stimulates lamina propria lymphocyte secretion of IL-22 and STAT3 signaling pathway	Hou et al. (2018)
	17938	Normal neonatal mice	Stimulates proliferation	Increases microbial phylogenetic diversity	Preidis et al. (2012)
Lactobacillus rhamnosus
	GG	Normal mouse colonic organoids, normal mouse	Stimulates colonic epithelial proliferation	Microbe-induced leptin expression triggers JAK-STAT signaling in a nox1 and leptin receptor-dependent manner	Darby et al. (2020), Jones et al. (2013)
	GG	Normal mouse	Stimulates ISC proliferation	Nox1-dependant reactive oxygen species generation	Lyu et al. (2022)
	GG	Intrauterine growth retardation rat pups	Stimulates proliferation and goblet cell differentiation	Stimulates WNT/β-catenin signaling	Banasaz et al. (2002)