ABSTRACT
Inulin, a commonly used dietary fiber supplement, is capable of modulating the gut microbiome. Chronic inflammation resulting from metabolic abnormalities and gut flora dysfunction plays a significant role in the development of type 2 diabetes mellitus (T2DM). Our research has demonstrated that inulin administration effectively reduced colonic inflammation in T2DM mice by inducing changes in the gut microbiota and increasing the concentration of butyric acid, which in turn modulated the function of enteric glial cells (EGCs). Experiments conducted on T2DM mice revealed that inulin administration led to an increase in the Bacteroidetes/Firmicutes ratio and the concentration of butyric acid in the colon. The anti-inflammatory effects of altered gastrointestinal flora and its metabolites were further confirmed through fecal microbiota transplantation. Butyric acid was found to inhibit the activation of the κB inhibitor kinase ß/nuclear factor κB pathway, regulate the expression levels of interleukin-6 and tumor necrosis factor-α, suppress the abnormal activation of EGCs, and prevent the release of inflammatory factors by EGCs. Similar results were observed in vitro experiments with butyric acid. Our findings demonstrate that inulin, by influencing the intestinal flora, modifies the activity of EGCs to effectively reduce colonic inflammation in T2DM mice.
ABSTRACT
BACKGROUND: The treatment outcome of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) varies greatly due to the clinical heterogeneity of the patients. Therefore, several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE (re-TACE). AIM: To investigate the correlations between prognostic systems and radiological response, compare the predictive abilities, and integrate them in sequence for outcome prediction. METHODS: This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016. The Hepatoma Arterial-embolization Prognostic (HAP) score system and its modified versions (mHAP, mHAP2 and mHAP3), as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival (OS) prediction for first TACE. The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART (assessment for re-treatment with TACE) and ABCR (alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response) systems for post re-TACE survival (PRTS). RESULTS: All the prognostic systems were correlated with radiological response achieved by first TACE, and the six-and-twelve criteria exhibited the highest correlation (Spearman R = 0.39, P = 0.026) and consistency (Kappa = 0.14, P = 0.019), with optimal performance by area under the receiver operating characteristic curve of 0.71 [95% confidence interval (CI): 0.68-0.74]. With regard to the prediction of OS, the mHAP3 system identified patients with a favorable outcome with the highest concordance (C)-index of 0.60 (95%CI: 0.57-0.62) and the best area under the receiver operating characteristic curve at any time point during follow-up; whereas, PRTS was well-predicted by the ABCR system with a C-index of 0.61 (95%CI: 0.59-0.63), rather than ART. Finally, combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo, compared with non-candidates with a median PRTS of 20.0 mo (log-rank test P < 0.001). CONCLUSION: Radiological response to TACE is closely associated with tumor burden, but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.