Decreases in
short-chain-fatty-acids (SCFAs) are linked to
inflammatory bowel disease (IBD). Yet, the mechanisms through which SCFAs promote wound healing, orchestrated by intestinal stem cells, are poorly understood. We discovered that, in mice with Citrobacter rodentium (CR)-induced infectious
colitis, treatment with
Pectin and
Tributyrin diets reduced the severity of
colitis by restoring Firmicutes and Bacteroidetes and by increasing mucus production.
RNA-seq in young adult mouse colon (YAMC) cells identified higher expression of Lgr4, Lgr6, DCLK1, Muc2, and SIGGIR after
Butyrate treatment. Lineage tracing in CR-infected Lgr5-EGFP-IRES-CreERT2/ROSA26-LacZ (Lgr5-R) mice also revealed an expansion of LacZ-labeled Lgr5(+) stem cells in the colons of both
Pectin and
Tributyrin-treated mice compared to control. Interestingly, gut microbiota was required for
Pectin but not
Tributyrin-induced Lgr5(+) stem cell expansion. YAMC cells treated with
sodium butyrate exhibited increased Lgr5 promoter reporter activity due to direct
Butyrate binding with Lgr5 at -4.0 Kcal/mol, leading to thermal stabilization. Upon ChIP-seq,
H3K4me3 increased near Lgr5 transcription start site that contained the consensus binding motif for a transcriptional activator of Lgr5 (SPIB). Thus, a multitude of effects on gut microbiome, differential gene expression, and/or expansion of Lgr5(+) stem cells seem to underlie amelioration of
colitis following dietary intervention.