Gluten-free diet affects fecal small non-coding RNA profiles and microbiome composition in celiac disease supporting a host-gut microbiota crosstalk.

Current treatment for celiac disease (CD) is adhering to a gluten-free diet (GFD), although its long-term molecular effects are still undescribed. New molecular features detectable in stool may improve and facilitate noninvasive clinical management of CD. For this purpose, fecal small non-coding RNAs (sncRNAs) and gut microbiome profiles were concomitantly explored in CD subjects in relation to strict (or not) GFD adherence over time. In this observational study, we performed small RNA and shotgun metagenomic sequencing in stool from 63 treated CD (tCD) and 3 untreated subjects as well as 66 sex- and age-matched healthy controls. tCD included 51 individuals on strict GFD and with negative transglutaminase (TG) serology (tCD-TG-) and 12 symptomatic with not strict/short-time of GFD adherence and positive TG serology (tCD-TG+). Samples from additional 40 healthy adult individuals and a cohort of 19 untreated pediatric CD subjects and 19 sex/age matched controls were analyzed to further test the outcomes. Several miRNA and microbial profiles were altered in tCD subjects (adj. p < .05). Findings were validated in the external group of adult controls. In tCD-TG-, GFD duration correlated with five miRNA levels (p < .05): for miR-4533-3p and miR-2681-3p, the longer the diet adherence, the less the expression differed from controls. tCD-TG+ and untreated pediatric CD patients showed a similar miRNA dysregulation. Immune-response, trans-membrane transport and cell death pathways were enriched in targets of identified miRNAs. Bifidobacterium longum, Ruminococcus bicirculans, and Haemophilus parainfluenzae abundances shifted (adj. p < .05) with a progressive reduction of denitrification pathways with GFD length. Integrative analysis highlighted 121 miRNA-bacterial relationships (adj. p < .05). Specific molecular patterns in stool characterize CD subjects, reflecting either the long-term GFD effects or the gut inflammatory status, in case of a not strict/short-time adherence. Our findings suggest novel host-microbial interplays and could help the discovery of biomarkers for GFD monitoring over time.

The small intestine: barrier, permeability and microbiota.

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.

Chronic hepatitis B virus infection and fibrosis: novel non-invasive approaches for diagnosis and risk stratification.

Despite the availability of an effective vaccination, chronic hepatitis B virus (HBV) infection is still a major health concern worldwide. Chronic HBV infection can lead to fibrosis accumulation and overtime to cirrhosis, the principal risk factor for liver failure and hepatocellular carcinoma development. Liver biopsy is still considered the gold standard for fibrosis assessment, even though it is invasive and not exempt of complications. Overtime, several non-invasive methods for the detection of liver fibrosis have been developed and gradually introduced into clinical practice. However, their main limitation is the poor performance for the detection of intermediate stages of fibrosis. Finally, novel serological biomarkers, polygenic risk scores and imaging methods have been proposed in last years as novel promising tools to correctly identify the degree of liver fibrosis and to monitor liver disease progression. In this narrative review, we provide an overview on the novel non-invasive approaches for the evaluation of liver fibrosis and risk stratification of patients with chronic hepatitis B.

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases.

In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn's disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25-18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.