In order to investigate the function of toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signal pathways in the pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D), IBS-D animal models were established in wistar rats challenged with acute and chronic stresses (29 days). Wistar rats without stress-challenged were used as controls. IBS-D models were randomly divided into two groups: one was treated with normal saline, another group was treated with TLR4/NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) (50mg/kg/week) for continuous four times. Our results demonstrate that continuous stresses can induce the characteristic symptoms of IBS-D, including high wet stool rate and intestinal flora imbalance. Further examinations of colon tissues show that the protein expression levels of TLR4 and NF-κB in IBS-D groups are higher than that in control group. The secretory levels of interleukin (IL-8), tumor necrosis factor α (TNFα), and myeloid differentiation factor 88 (MyD88) are significantly increased in IBS-D group. Administration with PDTC effectively downregulates levels of these inflammatory factors. In contrast, interleukin-10 (IL-10) is in an opposite alteration with lower levels in IBS-D groups and the PDTC treatment increases it to the levels as in control group. Moreover, inhibition of the TLR4/NF-κB by PDTC improves the microstructure of intestinal mucosa mainly by increasing the height of villi. Our results suggest that TLR4/NF-κB signal pathway plays an important role in the modulation of inflammatory responses in IBS-D, which might be a therapeutic target for the IBS-D. All of these findings also provide the evidence concerning an inherent linkage between the axis of stress/NF-κB/inflammation and IBS-D.

Our findings demonstrate that CUEDC2 plays an important role in protection from colonic inflammation, primarily by inhibiting the NF-κB and STAT3 signaling pathways and preventing excessive proliferation of the inflammatory epithelial cell.

Background: Several recent studies have reported the relationship between atherosclerosis and gut microbial imbalance. Small intestinal bacterial overgrowth (SIBO) is one of the most common forms of gut microbiota imbalance, and studies have shown that SIBO plays an important role in human health. However, the relationship between SIBO and subclinical atheromatous plaques remains unclear. The aim of this study was to investigate the frequency of subclinical atheromatous plaques in patients with SIBO and to explore the association between these two conditions. Methods: A total of 411 eligible subjects were included in this study. The lactulose hydrogen-methane breath test was used to diagnose SIBO, and ultrasound examinations of the carotid, abdominal aorta and lower extremity arteries were performed in all subjects to assess the presence of plaques. Results: Plaques were more common in the SIBO-positive group than in the SIBO-negative group (abdominal aorta, 74.2% vs. 38.8%, p < 0.01; carotid arteries, 71.7% vs. 52.3, p < 0.01; lower extremity arteries, 73.4% vs. 57.6%, p < 0.01). After adjusting for traditional confounders, compared to the SIBO-negative population, the SIBO-positive population had, respectively, OR = 4.18 (95% CI = 2.56–6.80, p < 0.001), OR = 1.93 (95% CI = 1.23–3.02, p = 0.004), OR = 1.81 (95% CI = 1.14–2.88, p = 0.011) and OR = 5.42 (95% CI = 2.78–10.58, p < 0.001) for abdominal, carotid, lower extremity and any-territory plaque presence. Conclusion: SIBO was found to be associated with subclinical atheromatous plaques, and the mechanism of this association warrants further exploration.

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