A red meat-derived glycan promotes inflammation and
cancer progression
A well known, epidemiologically reproducible risk factor for human
carcinomas is the long-term consumption of “red meat” of mammalian
origin. Although multiple theories have attempted to explain
this human-specific association, none have been conclusively
proven. We used an improved method to survey common foods
for free and glycosidically bound forms of the nonhuman sialic acid
N-glycolylneuraminic acid (Neu5Gc), showing that it is highly and
selectively enriched in red meat. The bound form of Neu5Gc is bioavailable,
undergoing metabolic incorporation into human tissues,
despite being a foreign antigen. Interactions of this antigen with
circulating anti-Neu5Gc antibodies could potentially incite inflammation.
Indeed, when human-like Neu5Gc-deficient mice were fed
bioavailable Neu5Gc and challenged with anti-Neu5Gc antibodies,
they developed evidence of systemic inflammation. Such mice are
already prone to develop occasional tumors of the liver, an organ
that can incorporate dietary Neu5Gc. Neu5Gc-deficient mice immunized
against Neu5Gc and fed bioavailable Neu5Gc developed
a much higher incidence of hepatocellular carcinomas, with evidence
of Neu5Gc accumulation. Taken together, our data provide
an unusual mechanistic explanation for the epidemiological association
between red meat consumption and carcinoma risk. This
mechanism might also contribute to other chronic inflammatory
processes epidemiologically associated with red meat consumption.