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INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a growing global health concern, as it has become the most prevalent chronic liver condition worldwide, currently estimated to affect up to 38% of the adult population. EVIDENCE ACQUISITION: MASLD is a complex disease impacting multiple systems, where systemic insulin resistance and related metabolic dysfunction play a pathogenic role in its development and progression of the disease. Despite its prevalence, MASLD is frequently under-recognized due to the lack of reliable non-invasive biomarkers for accurate diagnosis and staging, and effective treatments remain elusive. EVIDENCE SYNTHESIS: Growing evidence suggests that the gut microbiome significantly influences the occurrence and progression of MASLD due to gut dysbiosis. The Simulator of the Human Intestinal Microbial Ecosystem® (SHIME®) is a sophisticated gut models that mimics the entire gastrointestinal tract, incorporating stomach, small intestine, and different colon regions, each characterized by distinct physiology, anatomy, and microbial community. CONCLUSIONS: The SHIME® model emerges as a valuable tool for exploring therapeutic approaches based on gut microbiota management. This gastrointestinal simulator offers a unique platform for studying the complex interactions within the gut-liver axis. The ongoing development of this technology is expected to yield further insights into effective strategies for managing MASLD, improving patient outcomes through targeted microbiota interventions. [ABSTRACT FROM AUTHOR]

Plant-based diets (PBDs) are gaining attention as a sustainable and health-conscious alternative for managing various chronic conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). In the absence of pharmacological treatments, exploring the potential of lifestyle modifications to improve biochemical and pathological outcomes becomes crucial. The adoption of PBDs has demonstrated beneficial effects such as weight control, increased metabolic health and improved coexisting diseases. Nonetheless, challenges persist, including adherence difficulties, ensuring nutritional adequacy, and addressing potential deficiencies. The aim of this review is to provide a comprehensive overview of the impact of PBDs on MASLD, emphasizing the need for tailored dietary interventions with professional support to optimize their effectiveness in preventing and treating metabolic diseases. [ABSTRACT FROM AUTHOR]

Being two immune-mediated diseases (IMIDs), the association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is plausible, but data in the literature are conflicting. The aim of our study was to evaluate the possible association between IBD and MS in a cohort of patients with IBD. In a retrospective study, we examined the medical records of 5739 patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2022. Among these patients, we identified 14 with MS, with a prevalence of 0.24%. The reported prevalence of MS in the general population in Northern Italy in 2021 was 0.18% (p = 0.24). For each of the patients with MS identified, more than ten patients without MS were analyzed. The 14 MS cases were then compared with 342 controls. From the 14 patients with MS, 12 (85.7%) were female and 2 (14.3%) were male, while in the control group, 158 (46.2%) were female and 184 (53.8%) were male (p = 0.004). As for therapy, significant differences were found in mesalazine (5 (41.7%) cases vs. 317 (92.7%) controls, p < 0.0001) and anti-TNF treatment (0% cases vs. 26.6% controls, p = 0.03, respectively) at the time of MS diagnosis. Moreover, a Kaplan–Meier curve analysis showed that the 20-year survival probability was 98.4% for patients with IBD, while for patients diagnosed with MS and IBD it was 82.1% (p = 0.02). In conclusion, patients with IBD have a similar risk of developing MS compared to the general population, but female sex appears to increase the risk. Indeed, life expectancy at 20 years for patients with IBD and MS is lower than for patients with IBD alone. [ABSTRACT FROM AUTHOR]

Late chronotype, the individual's aptitude to perform daily activities late in the day, has been associated with low adherence to the Mediterranean diet (MedDiet) and metabolic syndrome. The aim of this work was to investigate the potential association of chronotype and adherence to the MedDiet with the liver fibrosis risk in patients with non-alcoholic fatty liver disease (NAFLD). Liver stiffness was assessed in 126 patients by FibroScan®530. Significant (F ≥ 2) and advanced (F ≥ 3) hepatic fibrosis were defined according to liver stiffness values ≥7.1 kPa and ≥8.8 kPa, respectively. Chronotype (MSFsc) was defined by the Munich Chronotype Questionnaire, and adherence to the MedDiet was defined by the Mediterranean diet score (MDS). Overall, the median age was 55 (46–63) years, and 57.9% of participants were male. The principal comorbidities were type-2 diabetes mellitus (T2DM) (26.1%), arterial hypertension (53.1%), dyslipidaemia (63.4%), obstructive sleep apnoea (5.5%) and depression (5.5%). Most subjects (65.0%) had intermediate + late chronotype and showed higher mid-sleep on workdays (p < 0.001) and on work-free days (p < 0.001) compared to those with early chronotype. In the logistic regression model, intermediate + late chronotype (p = 0.024), MDS (p = 0.019) and T2DM (p = 0.004) were found to be significantly and independently associated with the risk of both F ≥ 2 And F ≥ 3. We observed that the intermediate + late chronotype and low adherence to the MedDiet were associated with both significant and advanced liver fibrosis in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Non-alcoholic steatohepatitis (NASH) is a high-prevalence, rapidly growing form of non-alcoholic fatty liver disease (NAFLD), which is closely linked to obesity and metabolic disorders. Gut microbiota has been increasingly recognized as a key factor in the onset of NAFLD in recent years. The liver can be strongly influenced by changes in the gut microbiota through the portal vein, giving the gut-liver axis a very important role in understanding the pathophysiology of liver diseases. A healthy intestinal barrier is characterized by selective permeability to nutrients, metabolites, water and bacterial products and its impairment may be a predisposing or aggravating condition for the progression of NAFLD. In most cases, NAFLD patients follow a Western diet pattern, which is closely linked to obesity and associated metabolic diseases, promoting inflammation, structural and behavioral changes in the gut microbiota. In fact, factors such as age, gender, genetic or environmental factors may induce a dysbiotic microbiota that promotes epithelial barrier dysfunction and increased intestinal permeability, favoring the progression of NAFLD. In this context, new dietary approaches, such as prebiotics, are emerging to prevent disease and maintain health. In this review, we reported the role of the gut-liver axis in the pathogenesis of NAFLD and investigated the potential therapeutic effect of prebiotics on the enhancement of intestinal barrier dysfunction, hepatic steatosis and, consequently, the progression of NAFLD.

The study of intestinal permeability is gaining growing interest due to its relevance in the onset and progression of several gastrointestinal and non-gastrointestinal diseases. Though the involvement of impaired intestinal permeability in the pathophysiology of such diseases is recognized, there is currently a need to identify non-invasive biomarkers or tools that are able to accurately detect alterations in intestinal barrier integrity. On the one hand, promising results have been reported for novel in vivo methods based on paracellular probes, i.e., methods that can directly assess paracellular permeability and, on the other hand, on fecal and circulating biomarkers able to indirectly assess epithelial barrier integrity and functionality. In this review, we aimed to summarize the current knowledge on the intestinal barrier and epithelial transport pathways and to provide an overview of the methods already available or currently under investigation for the measurement of intestinal permeability.