Search

Background: In preclinical models of Type 1 Diabetes (T1D) the integrity of the gut barrier (GB) is instrumental to avoid dysregulated crosstalk between the commensal microbiota and immune cells and to prevent autoimmunity. The GB is composed of the intestinal epithelial barrier (IEB) and of the mucus layer containing mucins and antimicrobial peptides (AMPs) that are crucial to maintain immune tolerance. In preclinical models of T1D the alterations of the GB primarily affect the mucus layer. In human T1D increased gut permeability and IEB damage have been demonstrated but the integrity of the mucus layer was never assessed., Methods: We evaluated GB integrity by measuring serological markers of IEB damage (serological levels of zonulin) and bacterial translocation such as lipopolysaccharide binding protein (LBP) and myeloid differentiation protein 2 (MD2), and mRNA expression of tight junction proteins, mucins and AMPs in intestinal tissue of T1D patients and healthy controls (HC). Simultaneously, we performed immunological profiling on intestinal tissue and 16S rRNA analysis on the mucus-associated gut microbiota (MAGM)., Findings: Our data show a GB damage with mucus layer alterations and reduced mRNA expression of several mucins (MUC2, MUC12, MUC13, MUC15, MUC20, MUC21) and AMPs (HD4 and HD5) in T1D patients. Mucus layer alterations correlated with reduced relative abundance of short chain fatty acids (SCFA)-producing bacteria such as Bifidobacterium dentium, Clostridium butyricum and Roseburia intestinalis that regulate mucin expression and intestinal immune homeostasis. In T1D patients we also found intestinal immune dysregulation with higher percentages of effector T cells such as T helper (Th) 1, Th17 and TNF-α + T cells., Interpretation: Our data show that mucus layer alterations are present in T1D subjects and associated with dysbiosis and immune dysregulation., Funding: Research Grants from the Juvenile Diabetes Foundation (Grant 1-INO-2018-640-A-N to MF and 2-SRA-2019-680-S-B to JD) and from the Italian Ministry of Health (Grant RF19-12370721 to MF)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Ketone bodies (KB) might act as potential metabolic modulators besides serving as energy substrates. Bariatric metabolic surgery (BMS) offers a unique opportunity to study nutritional ketosis, as acute postoperative caloric restriction leads to increased lipolysis and circulating free fatty acids., Aim: To characterize the relationship between KB production, weight loss (WL) and metabolic changes following BMS., Methods: For this retrospective study we enrolled male and female subjects aged 18-65 years who underwent BMS at a single Institution. Data on demographics, anthropometrics, body composition, laboratory values and urinary KB were collected., Results: Thirty-nine patients had data available for analyses [74.4% women, mean age 46.5 ± 9.0 years, median body mass index 41.0 (38.5; 45.4) kg/m 2 , fat mass 45.2% ± 6.2%, 23.1% had diabetes, 43.6% arterial hypertension and 74.4% liver steatosis]. At 46.0 ± 13.6 d post-surgery, subjects had lost 12.0% ± 3.6% of pre-operative weight. Sixty-nine percent developed ketonuria. Those with nutritional ketosis were significantly younger [42.9 (37.6; 50.7) years vs 51.9 (48.3; 59.9) years, P = 0.018], and had significantly lower fasting glucose [89.5 (82.5; 96.3) mg/dL vs 96.0 (91.0; 105.3) mg/dL, P = 0.025] and triglyceride levels [108.0 (84.5; 152.5) mg/dL vs 152.0 (124.0; 186.0) mg/dL, P = 0.045] vs those with ketosis. At 6 mo, percent WL was greater in those with postoperative ketosis (-27.5% ± 5.1% vs 23.8% ± 4.3%, P = 0.035). Urinary KBs correlated with percent WL at 6 and 12 mo. Other metabolic changes were similar., Conclusion: Our data support the hypothesis that subjects with worse metabolic status have reduced ketogenic capacity and, thereby, exhibit a lower WL following BMS., Competing Interests: Conflict-of-interest statement: The authors have none to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Evidence has been obtained indicating that oxidation of low-density lipoproteins (LDL) plays a relevant role in the pathogenesis of atherosclerosis and it has been proposed that, due to the antigenic properties of oxidized LDL, the anti-oxLDL antibody titre could represent a useful index of in vivo LDL oxidation., Methods: Sixty-nine control subjects and 64 patients scheduled for selective coronary revascularization were investigated before surgery., Results: The coronary disease patients had a higher level of total plasma cholesterol, LDL cholesterol and triglycerides, and a lower level of HDL cholesterol. Plasma anti-oxLDL antibody titre was measured as the ratio of antibody binding to CuSO4-oxidised LDL versus native LDL. The antibody ratio was higher in coronary patients as compared with control subjects (1.56 +/- 0.5 vs 1.0 +/- 0.3, p < 0.01). A ratio higher than 1.34 (mean of controls +/- one standard deviation) was present in 60% of the coronary patients. Subclass analysis indicated that the presence of diabetes mellitus and hypercholesterolaemia (but not of hypertension, generalized arteriosclerosis, myocardial infarction and cigarette smoking) increased the anti-oxLDL antibody ratio to 1.72 +/- 0.4 and 1.68 +/- 0.3 respectively., Conclusion: The results obtained indicate that a) a high titre of anti-oxLDL antibodies is present in plasma of patients with coronary atherosclerosis, b) in these patients LDL oxidation takes place in vivo and probably plays a critical role in the development and progression of atherosclerosis.