Ketone BHB eases colitis via STAT6-driven M2 macrophages
IBD mucosa has lower β-hydroxybutyrate; giving BHB reduces DSS colitis severity by promoting STAT6-dependent M2 macrophage programs and mucosal repair.
Source
Ketone body β-hydroxybutyrate ameliorates colitis by promoting M2 macrophage polarization through the STAT6-dependent signaling pathway
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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.
What they did
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.
What they found
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.
The limits
What it doesn't show
Human data are observational for BHB levels; mouse DSS is acute, not chronic human IBD. Clinical ketone therapy safety/efficacy remain untested here.
Key terms
- β-hydroxybutyrate (BHB)
- Ketone body used as fuel and signaling metabolite.
- DSS colitis
- Dextran sulfate sodium mouse model of acute intestinal inflammation.
- M2 macrophage
- Alternatively activated macrophage associated with repair/anti-inflammation.
- STAT6
- Transcription factor downstream of IL-4/IL-13 required for BHB’s M2 effect here.
- AS1517499
- STAT6 inhibitor that abolishes BHB’s protective effects.
- DAI
- Disease activity index scoring colitis severity.
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Quiz yourself
BHB levels in IBD colonic mucosa are…
Common questions
Is BHB altered in human IBD tissue?
Yes—colonic mucosal BHB is significantly reduced and correlates with activity.
Does giving BHB help DSS colitis?
Yes—less weight loss, lower DAI, less shortening/histology damage.
What macrophage program is promoted?
M2-associated genes (IL-4Ra, IL-10, Arg-1, Chil3) via STAT6.
What blocks BHB’s benefit?
STAT6 inhibitor AS1517499 completely inhibits the protective effects.
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