There is now strong evidence implicating the enteric flora in the aetiopathogenesis of inflammatory bowel disease (IBD), and identification of CARD15 (NOD2) as a pattern recognition receptor (PRR) has given novel insights into host-bacteria interactions. CARD15 is implicated as the intracellular sensor of muramyl dipeptide, a highly conserved bacterial peptidoglycan motif, and raises the question of whether other PRRs are involved in the pathogenesis of Crohn’s disease (CD).

Toll-like receptor 4 (TLR4), in combination with CD14, LBP, and MD-2, acts as the PRR for the lipid A moiety of lipopolysaccharide, a major component of gram negative bacteria. Two common cosegregating polymorphisms of this gene have been described in humans, Asp299Gly and Thr399Ile. Asp299Gly has been associated with reduced bronchial responsiveness following lipopolysaccharide stimulation¹ although recent data have questioned the functional effect of this variant.²

We therefore note with interest the article of Franchimont and colleagues reporting the Asp299Gly frequency in a Belgian population with IBD (Gut 2004;53:987–92). Variant alleles were associated with both CD and ulcerative colitis (UC) in two cohorts and the allele was preferentially transmitted from carriers to affected …