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The human gut is an intensively colonized organ containing microorganisms that can be health-promoting or pathogenic. This feature led to the development of functional foods aiming to fortify the former category at the expense of the latter. Since long, cultured products, including probiotics fortification, have been used for humans as live microbial feed additions. This review presents some of the microbes used as probiotics and discusses how supplementation with probiotics may help initiate and/or restore eubiotic composition of gut microbiota. Additionally, it considers safety and regulatory aspects of probiotics.

Background: Glypican-3 (GPC-3) is a heparan sulfate proteoglycan overexpressed by hepatocellular carcinoma (HCC) cells. Several studies highlighted the diagnostic and prognostic value of GPC-3 expression in liver tissue, while data on the reliability of serum GPC-3 are limited and conflicting. We aimed to evaluate the prognostic value of serum GPC-3 in patients with HCC., Methods: A total of 449 patients (91 F and 358 M; median age 65 [38-86] years) with a new diagnosis of HCC and available serum samples collected at tumor diagnosis were retrospectively analyzed. All patients had cirrhosis and the main underlying etiology was viral (N.=323, 72%). Barcelona Clinic Liver Cancer (BCLC) staging system was adopted for patients' classification (BCLC 0/A, N.=293, 65% vs. B/C/D, N.=156, 35%) and treatment allocation. Response to therapy was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST)., Results: Median overall survival (OS) after HCC diagnosis was 30 months (95% confidence interval [CI]: 27-34). Patients with serum GPC-3>150 pg/mL showed lower overall survival (16; 95%CI: 13-24 months) compared to those with GPC-3≤150 pg/mL (36; 95%CI: 30-56 months) (Log-rank test, P<0.001). At multivariate Cox proportional-hazard regression analysis, presence of ascites (adjusted Hazard Ratio [aHR]=1.84; 95%CI: 1.23-2.74, P=0.003), BCLC stage (aHR=1.65; 95%CI: 1.39-1.97, P<0.001), mRECIST (aHR=0.33; 95%CI: 0.21-0.51, P<0.001) and GPC-3>150 pg/mL (aHR=2.02; 95%CI: 1.47-2.78, P<0.001) resulted significantly associated to overall survival., Conclusions: Serum GPC-3 resulted an independent prognostic factor for patients with HCC irrespectively from tumor stage and response to therapy.

In recent years, there has been growing interest in the comprehension of the physiology of intestinal permeability and microbiota; and how these elements could influence the pathogenesis of diseases. The term intestinal permeability describes all the processes that allow the passage of molecules as water, electrolytes and nutrients through the intestinal barrier by the paracellular or the transcellular transport systems with several implications for self-tolerance and not-self immunity. An increased permeability might induce a more significant interaction of the immune system with unknown external antigens. This might favor the onset of several immune-related extra-intestinal diseases including coeliac disease, diabetes mellitus type 1, bronchial asthma and inflammatory bowel diseases. Furthermore, the intestinal permeability interacts every day with microbiota, the complex system of mutualistic inhabitants and commensal microorganisms living in the healthy gut. Microbiota is implicated in physiological functions by actively participating in digestion, absorption, synthesis of vitamins and protection from external aggressions. The critical site where these processes occur is the small intestine to which this updated review is dedicated. Understanding its anatomy, its barrier structure and permeability modulation and its microbiota composition is the essential skill to comprehend the complex pathogenesis of several - not only gastroenterological - diseases.