Intestinal ischemia/reperfusion injury is a severe disease associated with a high mortality. The mechanisms that cause ischemia/reperfusion injury are complex and many factors are involved in the injury formation process; however, the only available treatment is surgical intervention. Recent studies demonstrated that the intestinal microbiome plays a key role in intestinal ischemia/reperfusion injury and there are many factors associated with intestinal bacteria during the formation of the intestinal ischemia/reperfusion injury. Among the Toll-like receptors (TLR), TLR2, TLR4, and their adaptor protein, myeloid differentiation primary-response 88 (MyD88), have been reported to be involved in intestinal ischemia/reperfusion injury. Oxidative stress and nitric oxide are also associated with intestinal bacteria during the formation of the intestinal ischemia/reperfusion injury. This review focuses on our current understanding of the impact of the microbiome, including the roles of the TLRs, oxidative stress, and nitric oxide, on intestinal ischemia/reperfusion injury.

Microbial molecular products incite intestinal inflammation by activating Toll-like receptors (TLRs) and inflammasomes of the innate immune system. This system's contribution to esophageal inflammation is not known. Gram-negative bacteria, which dominate the esophageal microbiome in reflux esophagitis, produce lipopolysaccharide (LPS), a TLR4 ligand. TLR4 signaling produces pro-interleukin (IL)1β, pro-IL18, and NOD-like receptor protein 3 (NLRP3), which prime the NLRP3 inflammasome. Subsequent NLRP3 inflammasome activation cleaves caspase-1, inducing secretion of proinflammatory cytokines and pyroptosis (inflammatory cell death). We explored LPS effects on NLRP3 inflammasome priming and activation in esophageal cells. We exposed esophageal squamous and Barrett's epithelial cells to LPS and measured the following: (1) TLR4, pro-IL1β, pro-IL18, and NLRP3 expression; (2) caspase-1 activity; (3) tumor necrosis factor-α, IL8, IL1β, and IL18 secretion; (4) lactate dehydrogenase (LDH) release (a pyroptosis marker); and (5) mitochondrial reactive oxygen species (ROS). As inhibitors, we used acetyl-Tyr-Val-Ala-Asp-CHO for caspase-1, small interfering RNA for NLRP3, and (2-(2,2,6,6,-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride for mitochondrial ROS. Squamous and Barrett's cells expressed similar levels of TLR4, but LPS induced TLR4 signaling that increased tumor necrosis factor-α and IL8 secretion only in Barrett's cells. Barrett's cells treated with LPS showed increased expression of pro-IL18, pro-IL1β, and NLRP3, and increased mitochondrial ROS levels, caspase-1 activity, IL1β and IL18 secretion, and LDH release. Acetyl-Tyr-Val-Ala-Asp-CHO, NLRP3 small interfering RNA, and Mito-TEMPO all blocked LPS-induced IL1β and IL18 secretion and LDH release. In Barrett's cells, LPS both primes and activates the NLRP3 inflammasome, causing secretion of proinflammatory cytokines and pyroptosis. By triggering molecular events promoting inflammation, the esophageal microbiome might contribute to inflammation-mediated carcinogenesis in Barrett's esophagus.

Background. Low-dose aspirin (LDA) is the most commonly prescribed antiplatelet agent for prevention of cardiovascular events following percutaneous coronary intervention (PCI). Long-term treatment with LDA has serious adverse effects, including gastrointestinal (GI) hemorrhage. Most studies have focused only on upper GI bleeding and few studies have evaluated the effect of LDA on total GI bleeding. Aims. The aims of this study were to investigate the incidence and risk factors of total GI bleeding within 30 days after PCI in Japanese patients taking LDA. Methods. A retrospective chart review was conducted for 364 patients undergoing LDA therapy following PCI at Osaka City University Hospital. A retrospective case-control study evaluated risk factors using the chi-squared test and logistic regression. Results. The incidence of total GI bleeding after PCI within 30 days was 4.3%. The source of the GI bleeding was located throughout the GI tract. Risk factors identified by univariate analysis were age ≥75 years, history of peptic ulcer disease, chronic renal failure, proton pump inhibitor use, and histamine H₂ receptor antagonist use. By multivariate logistic regression only age ≥75 years (odds ratio = 5.26; 95% confidence interval: 1.13–24.51; p = 0.035) was found to be an independent risk factor of GI bleeding. Conclusions. The incidence of GI bleeding in patients undergoing LDA therapy following PCI is high. The bleeding episodes were located in the upper, middle, and lower GI tract. Age of ≥75 years was an independent risk factor for GI bleeding after PCI in patients on LDA therapy.

Background & Aims The coronavirus disease 2019 (COVID-19) pandemic precipitated lifestyle changes. We aimed to clarify whether COVID-19–induced lifestyle changes affected the development of metabolic dysfunction–associated fatty liver disease (MAFLD). Methods This retrospective longitudinal study included 973 participants who underwent health checkups between 2018 and 2020. We used data from the MedCity21 health examination registry. Participants’ clinical characteristics and lifestyle habits were investigated. Independent lifestyle predictors of MAFLD development before the pandemic (2018–2019) and during the pandemic (2019–2020) were identified using logistic regression analysis. Results In 2018, 261 (27%) patients were diagnosed with MAFLD. Before the pandemic, 22 patients developed new MAFLD. During this time, routine late-night meals were identified as an independent lifestyle predictor of MAFLD development (hazard ratio [HR] 2.54, 95% confidence interval [CI] 1.02–6.36, P=0.046). In contrast, 44 patients developed new MAFLD during the pandemic. During this time, higher daily alcohol intake was identified as an independent lifestyle predictor of MAFLD development (HR 1.03, 95% CI 1.01–1.05, P=0.008). In participants aged <60 years, daily alcohol intake and the proportion of participants who ate 2 times/day were significantly higher in patients who developed MAFLD during the pandemic than in those who did not. In participants aged ≥60 years, no lifestyle habits were associated with MAFLD development before or during the pandemic. Conclusions New MAFLD diagnoses increased during the COVID-19 pandemic. Changes in lifestyle factors, particularly in those aged <60 years, must be monitored and addressed as the pandemic continues.

INTRODUCTION: No bowel preparation (BP) for colonoscopy achieves optimal efficacy and tolerability. Combining polyethylene glycol plus ascorbic acid (PEG-Asc) with adjuvants has been explored to enhance cleansing efficacy and reduce the required volume. The aim of this study was to evaluate whether adding 0.5 mg linaclotide to 1 L PEG-Asc (1 L-PEG/AL) improves superior cleansing compared with adding 24 mg senna (1 L-PEG/AS), which we previously reported to be noninferior to the standard regimen of 2 L PEG-Asc. METHODS: A multicenter, endoscopist-blinded, randomized controlled trial was conducted at 5 centers in Japan with outpatients scheduled for colonoscopy. The primary outcome was adequate BP, evaluated using the Boston Bowel Preparation Scale. Analyses were stratified based on low-risk and high-risk groups for inadequate BP. RESULTS: Between April 2022 and April 2023, 1,464 patients were randomized to the 1L-PEG/AL (n = 731) or 1L-PEG/AS (n = 733). The 1L-PEG/AL demonstrated higher adequate BP rates (92% vs 86%, P = 0.001) compared with 1L-PEG/AS. Both groups experienced similar adverse events and expressed high willingness for repeat BP (83% vs 81%, P = 0.49). In high-risk patients (n = 892), 1L-PEG/AL had significantly higher adequate BP rates (94% vs 86%, P < 0.001), whereas rates were comparably high in low-risk patients (n = 539) (94% vs 94%, P = 0.66). DISCUSSION: The linaclotide regimen was superior to the senna regimen reagrding BP efficacy without reducing tolerability. It can be a promising new option for BP, especially in patients at a high risk of inadequate BP.