A diet high in fermentable oligosaccharides, disaccharides, monosaccharides and polyphenols (FODMAPs) can exacerbate symptoms of IBS, but the mechanism of action is unknown. Zhou et al. fed rats a high FODMAP diet (HFD) and observed increases in faecal Gram-negative bacteria and serum lipopolysaccharide (LPS) levels, accompanied by increased intestinal inflammation, barrier dysfunction and visceral hypersensitivity. To test whether HFD-induced increases in LPS mediate the intestinal pathologies, LPS or faecal supernatant from HFD-fed rats was administered to treatment-naive rats. Similar intestinal barrier dysfunction and visceral hypersensitivity effects were seen, which were blocked by an LPS antagonist or by Toll-like receptor 4 knockdown. Furthermore, faecal LPS levels were found to be higher in patients with IBS (n = 6) than in healthy individuals (n = 6), and a low FODMAP diet was found to reduce LPS levels and improve symptoms in those with IBS.