Background: The disruption of the intestinal barrier and the imbalance of the gut microbiota (GM) seem to play a major role in the complex pathogenesis of irritable bowel syndrome (IBS). Specific microbial strains could improve the gut microenvironment, promoting anti-inflammatory pathways; similarly, vitamin D supplementation could play a role in enhancing the barrier integrity and modulating the immune response in the gut. This study aims to evaluate the efficacy of a new multistrain probiotic, combined with vitamin D, in improving gut barrier function in IBS without constipation. Methods: In this phase IIb double-blind randomized placebo-controlled, parallel-group, multicenter, clinical trial, 35 patients were treated for 12 weeks with OttaBac^®, a high concentration multistrain probiotic plus cholecalciferol, or placebo and were followed up until week 16. Symptoms, quality of life, intestinal permeability, fecal biomarkers, and microbiota composition were evaluated at 0, 12, and 16 weeks. Results: Mean zonulin values showed a significant progressive reduction in the active group (−10.2 ng/mL at week 12, p = 0.0375; −19.5 ng/mL at week 16, p = 0.0002), with a significant difference between groups at week 16 in the per-protocol population (−19.01, p = 0.0053). The active group showed a more stable trend toward improvement in stool frequency and consistency at both week 12 and 16, with a significant improvement compared to the baseline and to the placebo group (−23.2, p = 0.0265, and 5.57 vs. −23.2, p = 0.0492, respectively). No differences were found in regards to the lactulose/mannitol ratio, Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) and Short Form Health Survey (SF-36) total scores, plasmalemmal vesicle associated protein-1 (PV-1), and citrulline levels. In the active group, Bifidobacterium animalis subsp. lactis and Streptococcus thermophilus levels were increased (p < 0.05), while those for Lachnospira were decreased (p < 0.05), and significant changes in Actinobacteria and Proteobacteria were observed (p < 0.05). Lactate (p < 0.01) and acetate (p < 0.05) levels increased post-treatment. Correlation analysis pointed out a significant association between the microbial biomarkers and the symptoms (p < 0.05). Conclusions: Probiotic plus vitamin D could improve IBS-associated symptoms through gut microbiota modulation and gut barrier enhancement, with persistent benefits after treatment discontinuation.

Autobrewery syndrome is a rare condition characterized by the endogenous fermentation of carbohydrates by gut microbiota, which exceeds the liver’s detoxification capacity and leads to signs and symptoms of acute alcohol intoxication. This condition has significant clinical, social, and legal implications. Beyond the acute effects, the role of excessive endogenous ethanol production in the progression of chronic diseases—particularly liver disease—is still under investigation. In this review, we aim to describe the key clinical features of autobrewery syndrome, identify the main microbial pathogens involved, and explore the potential impact of endogenous ethanol production on the development and progression of chronic liver disease. Although robust data and standardized treatment protocols are currently lacking, we discuss the general principles of management and outline possible therapeutic strategies and future perspectives.

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape for hepatocellular carcinoma (HCC); however, a considerable proportion of patients do not achieve durable clinical benefits. This highlights the need for reliable predictive biomarkers, which are currently lacking. The accumulated evidence supports a relevant role of the gut–liver axis in modulating immunotherapy outcomes, and several studies have identified distinct microbial features associated with either responders or non-responders. Responders to immunotherapy frequently present with higher microbial diversity and enrichment of beneficial taxa, whereas the expansion of pro-inflammatory and pathogenic bacteria has been associated with primary resistance and increased treatment-related toxicity in non-responders. However, the available findings remain heterogeneous across cohorts, likely owing to differences in geography, diet, liver disease etiology, treatment regimens, and microbiome analytical methods. Machine-learning models integrating metagenomic and metabolomic data have shown encouraging results in defining microbial signatures associated with treatment outcomes, although variability among cohorts currently limits their clinical applicability and generalizability. Beyond microbial taxonomic composition, microbiota-derived metabolites—such as short-chain fatty acids, bile acids, inosine, and tryptophan catabolites—appear to play a crucial role in shaping the tumor microenvironment and host immune responses, thus representing additional candidate biomarkers, also due to the relative ease of their measurement. Finally, microbiota-targeted interventions are emerging as potential strategies to enhance immunotherapy efficacy. Overall, the gut microbiome and its metabolic activity represent promising tools, albeit still under investigation, for patient stratification and personalized management in HCC treated with ICIs. Therefore, this review aims to summarize and critically discuss the current evidence on gut microbiota-derived biomarkers of response and resistance to ICIs in HCC, with particular focus on microbial composition, microbiota-related metabolites, and emerging microbiome-based therapeutic strategies. This narrative review provides an updated overview of the role of gut microbiota as both a biomarker and a therapeutic target in patients with hepatocellular carcinoma (HCC) receiving immune checkpoint inhibitor (ICI) therapy.

Background: Lynch syndrome (LS) is a genetic disease with increased risk of colorectal cancer and other malignancies. There are few reported cases of thyroid cancer in LS patients. The aim of this study is to investigate the presence of thyroid nodules in LS patients and to explore their association with the genetic features of the disease. Methods: A retrospective and descriptive analysis was conducted to include all LS patients followed at the CEMAD (Centro Malattie Apparato Digerente) of Fondazione Policlinico Universitario A. Gemelli IRCCS. The characteristics of LS disease, gene mutations, and previous history of thyroid disease were evaluated. Majority of patients underwent thyroid ultrasound (US), and nodule cytology was performed when needed. Results: Of a total of 139 patients with LS, 110 patients were included in the study. A total of 103 patients (74%) underwent thyroid ultrasound examinations, and 7 patients (5%) had a previous history of thyroid disease (cancer or multinodular goiter). The mean age was 51.9 years. Thyroid nodules were found in 62 patients (60%) who underwent US, and 9 of them (14%) had suspicious features of malignancy, inducing a fine-needle aspiration biopsy. A cytologic analysis classified 7 of 9 cases (78%) as TIR2 and 2 (22%) as TIR3a. Between patients with nodular thyroid disease (single nodule, multinodular goiter, and cancer), most of them (25 patients, 36% of total) were carriers of the MSH6 mutation, while 22 (32%), 17 (24%), and 5 (7%) had MSH2, MLH1, and PMS2 mutations, respectively. Conclusions: A high prevalence of thyroid nodules was found in patients with LS, especially in MSH6-carrying patients. Performing at least one thyroid ultrasound examination is suggested for the detection of nodular thyroid disease in LS patients. Systematic investigations are needed to estimate their prevalence, features, and risk of malignant transformation.

Recent advancements in understanding how cancer cells evade immune recognition have led to significant progress in cancer immunotherapy. Therapeutic cancer vaccines hold great promise due to their safety, specificity, and ability to establish lasting immune memory, serving as an effective immunotherapy either alone or in combination with other treatments in clinical research. Cancer vaccines aim to restore the host’s innate and adaptive anti-cancer immune responses by stimulating antigen-presenting processes and reversing the immunosuppressive environment that facilitates tumor immune evasion and metastasis. Although in clinical studies cancer vaccines have been observed to not effectively induce tumor regression, they can enhance local immune responses in combination with other immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), thus delaying cancer recurrence and prolonging overall survival in advanced tumor settings.

Background/Objectives: Severe asthma remains difficult to treat, even with the range of biologics we now have that target type 2 inflammation. Some patients do not respond well enough to the first biologic they try, which raises the question of whether switching to another option can help. In this study, we looked at how patients who had unsatisfactory therapeutic outcomes on other biologics responded—both clinically and at the biomarker level—after switching to dupilumab. Methods: We reviewed data from the Allergy and Clinical Immunology Unit of Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy, between January and June 2025. The study included fifteen adults with uncontrolled severe asthma who had previously been treated for at least six months with benralizumab, omalizumab, or mepolizumab before switching to dupilumab. We evaluated demographic, clinical and laboratory data. Lung function (Forced Expiratory Volume in 1 s (FEV₁)), blood eosinophils, total and specific IgE to staphylococcal enterotoxins, eosinophil cationic protein (ECP), free light chains (FLC), and FeNO were assessed at the time of the switch and again after 12 months. Comparisons were made using paired tests, and a p-value < 0.05 was considered statistically significant. Results: After a year on dupilumab, we saw clear improvements: mean FEV₁ went up by about 10.8% predicted (p = 0.002), FeNO dropped by an average of 22 ppb (p = 0.005), blood eosinophils fell by roughly 400 cells/µL (p = 0.003), and ECP levels decreased by 13 µg/L (p = 0.009). Kappa FLCs also showed a significant drop (p = 0.04). Clinically, 40% of patients met criteria for a meaningful response, and 20% achieved complete remission. Dependence on oral corticosteroids was notably reduced. Baseline levels of eosinophils, ECP, IgE, and FLCs correlated with response to treatment. Conclusions: Our study, despite the small sample size, highlights that in patients with severe asthma who do not show a good response to their first biologic, switching to dupilumab can lead to significant improvements. Markers of type 2 inflammation at baseline might help predict who benefits most. Larger, multi-center, prospective studies are needed to confirm these results.