Short-chain fatty acids (SCFA) are produced by fermentation of water-soluble fiber by anaerobic bacteria in the large bowel. Fiber-rich diets decrease the risk of developing
inflammatory bowel disease (IBD) and
butyrate enemas are effective as a
therapy in some patients.
Crohn's disease, one form of IBD, appears to involve an exagerated T helper-1 (Th1) lymphocyte phenotype, characterised by production of
interleukin (IL)-2 and
interferon (IFN)-gamma, that drives the
inflammation. To examine whether SCFA influence pro- and anti-inflammatory
cytokine production, rat mesenteric lymph node lymphocytes were cultured in the presence of
acetate (10 mM),
butyrate (1.5 mM) or
propionate (2 mM) and the production of
cytokines in response to
concanavalin A determined.
Butyrate, but not
acetate or
propionate, inhibited lymphocyte proliferation and
IL-2 production.
Acetate and
propionate were able to partly prevent the inhibitory effect of
butyrate on
IL-2 production.
Acetate and
propionate increased IFN-gamma production, whereas
butyrate inhibited it.
Acetate and
propionate in combination were able to prevent the inhibitory effect of
butyrate on IFN-gamma production.
IL-4 was not detected in any cultures.
Acetate and
propionate increased
IL-10 production, which was not affected by
butyrate. It is concluded that
butyrate significantly inhibits Th1-type responses and that this might explain the
therapeutic effect of
butyrate in IBD patients.
Acetate and
propionate have less marked modulatory actions, and in some cases have effects that oppose those of
butyrate. A combination of the three SCFA causes a shift in the T helper lymphocyte phenotype towards a more anti-inflammatory phenotype and this might explain the protective effects of fiber.