FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated intestinal inflammation and barrier dysfunction
Shi-Yi Zhou, Merritt Gillilland III, Xiaoyin Wu, Pornchai Leelasinjaroen, Guanpo Zhang, Hui Zhou, Bo Ye, Yuanxu Lu, Chung Owyang
Shi-Yi Zhou, Merritt Gillilland III, Xiaoyin Wu, Pornchai Leelasinjaroen, Guanpo Zhang, Hui Zhou, Bo Ye, Yuanxu Lu, Chung Owyang
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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 8

Effects of LFM on WAS-induced mucosal inflammation, permeability alteration, and visceral hypersensitivity.

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Effects of LFM on WAS-induced mucosal inflammation, permeability alterat...
(A) Real-time quantitative RT–PCR measurement of colonic cytokine levels in rats subjected to sham WAS, WAS, or WAS+LFM. WAS increased IL-1β, IL-6, IL-17, TNF-α, and IFN-γ gene expression, indicating low-grade mucosal inflammation. WAS increased colon permeability, as measured by TEER (B) and the appearance of FITC–dextran in serum (C), and was accompanied by increased serum LPS, indicating endotoxemia (D). WAS caused a decrease in ZO-1 expression (E) and visceral hypersensitivity (F). LFM prevented WAS-induced changes in cytokine levels, gut permeability, and visceral hypersensitivity. n = 6 per group. *P < 0.05 versus sham WAS; #P < 0.05 versus WAS. AUC, area under the curve; EMG, electromyographic activity; LFM, low-FODMAP diet; LPS, lipopolysaccharide; TEER, transepithelial electrical resistance; WAS, water avoidance stress. P < 0.05, by 2-tailed Student’s t test or 2-way repeated-measures ANOVA.