Metabolism
Ketone BHB eases colitis via STAT6-driven M2 macrophages
Open access · cc by · source: Europe PMC
IBD mucosa has lower β-hydroxybutyrate; giving BHB reduces DSS colitis severity by promoting STAT6-dependent M2 macrophage programs and mucosal repair.
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Ketone BHB eases colitis via STAT6-driven M2 macrophages
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Exogenous BHB alleviates acute DSS colitis severity metrics
we demonstrated that the administration of exogenous BHB alleviated the severity of acute experimental colitis, which was characterized by less weight loss, disease activity index, colon shortening, and histology scores, as well as decreased crypt loss and epithelium damage.
BMDM experiments used 5 mM BHB with IL-4
In IL-4 plus BHB group, BMDMs were treated with 100 ng/mL IL-4 and 5 mM BHB together for 48 h.
Key findings
Mucosal BHB was reduced and tracked IBD activity. Exogenous BHB lessened weight loss, DAI, shortening, and epithelial damage while raising M2 genes (IL-4Ra, IL-10, Arg-1, Chil3). BHB boosted STAT6 phosphorylation and M2 programs in vitro; AS1517499 blocked anti-inflammatory/repair benefits.
Methodology
Huang et al. measured BHB in IBD vs control colonic mucosa, treated DSS colitis mice with exogenous BHB (assessing weight, DAI, colon length, histology), profiled M2 genes/microbes, and tested BMDMs with IL-4 ± 5 mM BHB and STAT6 inhibitor AS1517499.
Limitations
Human data are observational for BHB levels; mouse DSS is acute, not chronic human IBD. Clinical ketone therapy safety/efficacy remain untested here.
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