FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated intestinal inflammation and barrier dysfunction
Shi-Yi Zhou, … , Yuanxu Lu, Chung Owyang
Shi-Yi Zhou, … , Yuanxu Lu, Chung Owyang
Published November 27, 2017
Citation Information: J Clin Invest. 2018;128(1):267-280. https://doi.org/10.1172/JCI92390.
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Research Article Gastroenterology

FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated intestinal inflammation and barrier dysfunction

Abstract

Foods high in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) exacerbate symptoms of irritable bowel syndrome (IBS); however, their mechanism of action is unknown. We hypothesized that a high-FODMAP (HFM) diet increases visceral nociception by inducing dysbiosis and that the FODMAP-altered gut microbial community leads to intestinal pathology. We fed rats an HFM and showed that HFM increases rat fecal Gram-negative bacteria, elevates lipopolysaccharides (LPS), and induces intestinal pathology, as indicated by inflammation, barrier dysfunction, and visceral hypersensitivity (VH). These manifestations were prevented by antibiotics and reversed by low-FODMAP (LFM) diet. Additionally, intracolonic administration of LPS or fecal supernatant (FS) from HFM-fed rats caused intestinal barrier dysfunction and VH, which were blocked by the LPS antagonist LPS-RS or by TLR4 knockdown. Fecal LPS was higher in IBS patients than in healthy subjects (HS), and IBS patients on a 4-week LFM diet had improved IBS symptoms and reduced fecal LPS levels. Intracolonic administration of FS from IBS patients, but not FS from HS or LFM-treated IBS patients, induced VH in rats, which was ameliorated by LPS-RS. Our findings indicate that HFM-associated gut dysbiosis and elevated fecal LPS levels induce intestinal pathology, thereby modulating visceral nociception and IBS symptomatology, and might provide an explanation for the success of LFM diet in IBS patients.

Authors

Shi-Yi Zhou, Merritt Gillilland III, Xiaoyin Wu, Pornchai Leelasinjaroen, Guanpo Zhang, Hui Zhou, Bo Ye, Yuanxu Lu, Chung Owyang

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Figure 9

Effects of fecal supernatant from IBS-D patients on visceral sensitivity.

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Effects of fecal supernatant from IBS-D patients on visceral sensitivity...
(A) Endotoxin level in fecal contents was elevated in IBS-D compared with HS (n = 6). (B) Representative electromyogram recordings of responses to colorectal distension showing that an intracolonic infusion of fecal supernatant from IBS-D patients induced visceral hyperalgesia in naive rats. This action was abolished by LPS-RS or treatment with low-FODMAP diet. (C) Bar chart showing that an intracolonic infusion of fecal supernatant from IBS-D patients induced visceral hyperalgesia in naive rats; this was prevented by LPS-RS or treatment with 4 weeks of low-FODMAP diet. Mean amplitudes of abdominal muscle contractions are expressed as area under the curve (AUC) after baseline subtraction (n = 5 per group). *P < 0.05 compared with HS; #P < 0.05 compared with IBS (IBS-D); ‡P < 0.05 and †P < 0.05 compared with IBS. HC, healthy controls; HS, healthy subjects; LFM, low-FODMAP diet; LPS, lipopolysaccharide; LPS-RS, LPS antagonist. P < 0.05, by 2-tailed Student’s t test or 2-way repeated-measures ANOVA.