Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function. Short-chain fatty acids (SCFAs)

as metabolites of the gut microbiota

protect the physiological intestinal barrier; however

they are compromised when VA is deficient. Thus

there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD). Herein

compared with normal VA rats (VAN)

at the beginning of pregnancy

we confirmed that the colonic desmosome junction was impaired in the VAD group

and the amounts of acetate

propionate

and butyrate declined because of the decreased abundance of SCFA-producing bacteria (

Romboutsia

Collinsella

and

Allobaculum

). The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA sequencing. In the VAD group

the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated

and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were up-regulated. Intriguingly

the above changes in the VAD groups were rescued by VA supplementation in the early postnatal period. Further study indicated that in Caco-2 cells

butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the

CEACAM1

gene to induce its expression. Our findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD

and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.