Gastroenterology Insights

Background: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are considered major causes of cancer-related mortality. Evidence suggests that gut microbiome dysbiosis and the microbial–metabolic axis and its metabolites in hepatic chronic inflammation might be implicated in carcinogenesis in the gut–liver axis. This descriptive systematic review examines the microbial–metabolic axis in hepatobiliary cancer, focusing on patterns of dysbiosis, microbiome-associated metabolites, and the diagnostic or prognostic potential in this field. Methods: This manuscript was developed according to PRISMA 2020 guidelines and registered in PROSPERO (CRD420261455009). PubMed, Scopus, Cochrane Library, Web of Science, and Embase were searched. Eligible studies were published medical manuscripts reporting gut (oral/duodenal/fecal) microbiome alterations with links to HCC or CCA. Risk of bias was assessed with Rob 2.0 for the randomized clinical trial study included in this manuscript and ROBINS-I for the non-randomized studies. Ultimately, 13 studies met the inclusion criteria and were included in this qualitative study. Results: In the included studies, patients with HCC or CCA showed altered gut microbial diversity, a depletion of beneficial taxa such as Faecalibacterium and Bifidobacterium, and increased levels of potentially pro-inflammatory genera. Specific signatures such as Alloprevotella and the B.F.R. genera models in CCA were associated with diagnostic performance, with AUCs that frequently exceeded 0.90 in internal validation. Furthermore, circulating and host microbial metabolites, such as methionine, methionine sulfoxide, taurocholic acid, and microbial-derived TMA/TMAO pathway components, were associated with HCC risk. Conclusions: According to our analysis, gut microbiome alterations are associated with HCC and CCA and show promising diagnostic and prognostic potential. The findings are consistent with a possible microbial–metabolic contribution to hepatocarcinogenesis through chronic inflammatory and metabolic pathways. However, most included studies evaluated virus-related liver disease, and direct evidence linking obesity or MASLD-related dysbiosis to hepatobiliary cancer remains limited. Prospective and interventional investigations of metabolic liver disease populations are needed to clarify this axis.

Although overall colorectal cancer (CRC) incidence and mortality have declined with widespread screening, early-onset CRC (EOCRC), defined as diagnosis before age 50, continues to rise. EOCRC partially differs from late-onset CRC (LOCRC) in clinical presentation, molecular features, polyp characteristics, and patterns of modifiable risk factors; however, the extent to which these differences reflect distinct underlying biology remains uncertain. Despite updated recommendations from the 2018 American Cancer Society and 2021 U.S. Preventive Services Task Force to initiate average-risk screening at age 45, fewer than 21% of eligible adults aged 45–49 years old were up to date with screening in 2021, highlighting a substantial gap in uptake. Emerging data on epidemiologic patterns, molecular features, and risk modifiers offer opportunities to refine personalized risk prediction tools and optimize early detection. This review synthesizes current evidence on EOCRC biology and risk factors, evaluates evolving screening guidelines across professional societies, and examines barriers to screening, including access disparities, limited awareness, and psychosocial factors, thus emphasizing the urgent need to improve implementation and risk-based prevention strategies.

Obesity is a chronic inflammatory condition whose rising incidence has turned it into a global epidemic, a trend that also affects people living with inflammatory bowel diseases (IBD). Recent epidemiological data indicate that roughly 25 to 40% of patients with IBD are overweight and that 15 to 40% have obesity. Obesity can contribute to the pathogenesis of IBD and acts as a negative prognostic factor for disease course, response to pharmacological treatment, hospitalizations, post-surgical complications, and quality of life. Overall, the rate of adverse events related to the intestinal disease is higher in patients with obesity, and early data suggest that exposure to weight-loss interventions is associated with more favourable disease outcomes. The relationship between obesity and IBD is complex and involves systemic inflammation, increased production of proinflammatory cytokines, greater intestinal permeability, microbiota alterations, dietary patterns, and hormonal changes. Weight loss interventions, including lifestyle modification, pharmacological treatment, and bariatric surgery, appear to influence IBD-related outcomes, with growing attention to the emerging role of glucagon-like peptide-1 (GLP-1) receptor agonists. Several questions remain open and could guide future research, since a full understanding of the interplay between IBD and obesity is crucial for effective personalized treatment.