Table 3.

The role of REG/Reg family in inflammation-related intestinal diseases.

Member	Correlation with microecology	Conclusion	Ref.
REG4/Reg4	In Reg4-KO mouse, intestinal Lactobacillus abundance decreases; In human REG4-transgenic mouse, intestinal Lactobacillus reuteri abundance increases.	REG4 modulates gut microbiota metabolite CLA and downstream signaling pathways to regulate intestinal immune homeostasis, sustaining IL-35+ macrophage function.	[63]
Reg3β	Antibiotic treatment decreases SCFA levels; Clostridium abundance correlates closely with propionate levels and Reg3β/γ expression.	Clostridium-derived propionate maintains intestinal epithelial homeostasis through Reg3β and GPR43 signaling, with the Reg3β-propionate axis serving as a key regenerative mediator in colitis.	[76]
Reg3β/γ	Reg3β/γ expression positively correlates with A. muciniphila, Lachnospiraceae_NK4A136_group, and Bacteroidetes, but negatively with Firmicutes, Blautia, and Butyricimonas.	Polyphenol-rich vinegar extract reduces alcohol-induced oxidative stress and hepatic/intestinal inflammation by modulating gut microbiota, boosting intestinal immunity/AMPs, and blocking inflammatory pathways.	[77]
Reg3γ	In feces of TAGAP-deficient mouse, Bacteroides acidifaciens abundance is higher than controls, while A. muciniphila first decreases then abnormally increases with aggravated inflammation.	TAGAP “TAGAP-Reg3γ-gut microbiota-Th1 differentiation” pathway; its dysfunction is a key mechanism for IBD development.	[85]
Reg3β/γ	In germ-free Card9-deficient mouse, colonic Reg3βγ expression is markedly reduced; after transplanting mouse microbiota into adult Card9-deficient mice, Reg3βγ and IL-22 remain lower than WT.	In germ-free Card9-deficient Mouse, colonic Reg3βγ expression is markedly reduced; after transplanting mouse microbiota into adult Card9-deficient mice, Reg3βγ and IL−22 remain lower than WT.	[106]
REG3γ	STING agonists alleviate Citrobacter-induced colitis in Mouse, dependent on REG3γ expression.	STING enhances intestinal epithelial antimicrobial defense via the "STAT3-glycolysis -REG3γ" axis, revealing its protective role in intestinal infection and IBD.	[127]
REG3 Reg3β/γ	In intestines of IBD patients, Enterococcus faecium and diversity are significantly reduced, and negatively correlated with REG3A concentration.	In IBD, excess REG3 depletes intestinal E. faecium, reducing SagA secretion. NOD2 activation in myeloid cells, lowers IL-1β and IL-22, thereby perpetuating a cycle of excessive Reg3β/γ, beneficial bacteria loss, and chronic inflammation.	[131]
REG3γ	In the FMT group of mouse, beneficial Lactobacillus increases, while harmful Clostridium_sensu_stricto_1 and Turicibacter decrease.	FMT treats colitis by regulating gut microbiota composition and expression of REG3γ.	[133]
REG3G	Roseburia hominis abundance is significantly negatively correlated with REG3G expression.	Microbiota dysbiosis and host defense defects synergistically drive UC's vicious cycle; REG3G may inform UC therapeutic strategies.	[109]