Agave fructans enhance the effects of fermented milk products on obesity biomarkers: a randomised trial.

Dysbiosis has been implicated in childhood obesity. Oral intake of fermented milk containing Lacticaseibacillus casei strain Shirota preserves gut microbiota (GM) diversity in children and adults. This study was a double-blind trial involving 37 overweight or obese children aged 6-10 years. Children were followed over a 6-week intervention period in which they received different fermented milk products containing L. casei Shirota: 10 in the first group received just L. casei Shirota; 13 received L. casei Shirota with 3 g/day of inulin (L. casei+inulin); and 14 received L. casei Shirota with 3 g/day of fructans from Agave salmiana (L. casei+fructans). Principal component analysis showed the relationship between microbial abundance, GM metabolites, and other obesity-related markers. Supplementation with probiotics and synbiotics improved the HDL-cholesterol levels of overweight and obese children, although no changes in body composition were detected. We observed an increase in butyrate or propionate concentrations in the L. casei+fructans group compared to the end of the intervention (P<0.03). A diminished level of ANGPTL4 within the L. casei+fructans group (P=0.04) was also found, but no differences when lipopolysaccharide-binding protein was evaluated. The FFAR2+ cell frequency decreased between baseline and at the end of 6-week intervention in L. casei+inulin (P=0.02) and L. casei+fructans groups (P=0.04). In contrast, the percentage of CD14+FFAR3+ frequency increased in the same groups (P=0.04). The L. casei Shirota with inulin or fructans modulates GM, which improves the lipid profile and changes at a molecular level, such as expression of FFAR3 and FFAR2, ANGPTL4, propionate, and butyrate. It, therefore, could be considered an interesting therapeutic possibility for treating childhood overweight and obesity. The study was registered at ClinicalTrials.gov (ID: NCT05423015).

B regulatory cells associated with changes in biochemical and inflammatory parameters in normal-glycemic individuals, pre-diabetes and T2DM patients.

AIM: To determine the percentages of (CD19 + CD24 + CD38+, CD19 + CD24 + CD27+, CD19 + IL-10+)-Breg cells, IL-17 single and IL-17+/IFN-γ double producers T cells and IFN-γ+ T cells, in normal-glycemic individuals, prediabetes and T2DM patients, and to analyze the association of Breg cells with metabolic parameters of T2DM. METHODS: percentages of Breg cells, IL-17+ and IL-17 + IFN-γ+ T cells, IFN-γ+ T cells and IL-10 were determined by flow cytometry. IL-6 levels were evaluated by ELISA assay. RESULTS: increased IL-6 levels, IL-17+ and IL-17 + IFN-γ+ T cells and a diminution of IL-10 levels and CD19 + IL-10+ cells in T2DM patients were observed. We found that CD19 + CD24 + CD27+ cells and CD19 + CD24 + CD38+ cells were increased in T2DM patients. The percentages of CD19 + CD24 + CD38+ cells were associated with HOMA-B, TyG index, HDL and cholesterol values. In normal-glycemic individuals, CD19 + CD24 + CD27+ cells were inversely associated to triglycerides and TyG index. In prediabetes patients, CD19 + CD24 + CD38+ cells were inversely related with cholesterol and LDL. Finally, CD19 + CD24 + CD38+ cells were inversely related with HDL values in T2DM patients. CONCLUSION: Our results suggest that increased percentages of IL-17 single and IL-17/IFN-γ double producers T cells in T2DM patients may be a consequence of the initial CD19 + IL-10+ cells reduction. Furthermore, dyslipidemia could play an important role in percentages and activity of B regulatory cells.

Identification of putative miRNA biomarkers in early rheumatoid arthritis by genome-wide microarray profiling: A pilot study.

Despite the existing research, the etiology of rheumatoid arthritis (RA), an autoimmune disease remains poorly understood with early and accurate diagnosis difficult to achieve. MicroRNAs (miRNAs) play an important role in biological processes as modulators of transcription and translation. Previous studies have demonstrated a downregulation of several genes in early RA stages and in addition, miRNAs may serve as early biomarkers of subclinical changes in early RA. When comparing the four groups (ANOVA P < 0.01, fold change > 4), we found 253 differentially expressed miRNAs. Of these, 97 miRNAs were identified as overexpressed in early rheumatoid arthritis. The validation of miRNA microarray expression was performed in a set by RT-qPCR and showed strong agreement with microarray expression data. The putative targets of overexpressed microRNAs in early RA were significantly enriched in apoptosis, tolerance loss and Wnt pathways. Moreover, ROC analysis showed values of AUC 0.76 and P < 0.05 for miR 361-5p, identifying this miRNA as a potential biomarker of disease. We identified specific microRNAs associated with early rheumatoid arthritis and proposed them as early biomarkers of disease. Our results provide novel insight into immune disease physiopathology and describe unreported microRNAs in RA with potential for clinical use.