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Analysis of gut barrier status, monocyte and lymphocyte activation and T regulatory (Treg) cells at diagnosis before and after therapy, in patients with multiple sclerosis (MS). Analysis of differential effects of interferon beta (IFN-β), glatiramer acetate (GA) and natalizumab. Thirty-five patients with untreated MS were included. Gut barrier status (serum concentrations of intestinal fatty acid binding protein), monocyte (serum levels of soluble CD14, soluble CD163 and interleukin 6) and T lymphocyte activation (CD4 + DR+ and CD8 + DR+) and Treg (CD4 + CD25highFoxP3+) cells were analyzed. Patients with clinical isolated syndrome and relapsing-remitting forms were treated with IFN-β or GA, and immune characteristics were reevaluated following up after 6 months. A sample of 56 stable RR MS patients, in treatment with IFN-β, GA or natalizumab, and 50 healthy individuals were included as controls. Gut barrier status was similar in MS patients and healthy controls. Untreated patients with relapsing-remitting and primary progressive patterns of MS showed increased serum levels of soluble CD14. At baseline, significant increases in activated T lymphocytes and Treg were detected in patients. A significant decrease of CD4 + DR+, CD8 + DR+, and Treg percentages after 6 months of therapy was observed. In previously treated patients, IFN-β, GA, or natalizumab therapies were associated with a comparable cell proportion of activated lymphocytes and Treg. MS patients have a baseline state characterized by monocyte and lymphocyte activation, not related with gut barrier lesion. An increase in Treg number, correlated with activated T CD8+ lymphocytes, was detected. Treatment with IFN-β, GA or natalizumab was associated with a comparable decrease in activated lymphocytes and Treg. [ABSTRACT FROM AUTHOR]

Rationale: Researchers in psychiatry and neuroscience are increasingly recognizing the importance of gut-brain communication in mental health. Both genetics and environmental factors influence gut microbiota composition and function. This study examines host-microbe signaling at the gastrointestinal barrier to identify bottom-up mechanisms of microbiota-brain communication. Objectives: We examined differences in gut microbiota composition and fecal miRNA profiles in BALB/c and C57BL/6 mice, in relation to gastrointestinal homeostasis and evaluated the response to perturbation of the gut microbiota by broad-spectrum antibiotic treatment. Methods and results: Differences in the gut microbiota composition between BALB/c and C57BL/6 mice, evaluated by fecal 16S rRNA gene sequencing, included significant differences in genera Prevotella, Alistipes, Akkermansia, and Ruminococcus. Significant differences in fecal miRNA profiles were determined using the nCounter NanoString platform. A BLASTn analysis identified conserved fecal miRNA target regions in bacterial metagenomes with 14 significant correlations found between fecal miRNA and predicted taxa relative abundance in our dataset. Treatment with broad-spectrum antibiotics for 2 weeks resulted in a host-specific physiological response at the gastrointestinal barrier including a decrease in barrier permeability in BALB/c mice and alterations in the expression of barrier regulating genes in both strains. Genera Parabacteroides and Bacteroides were associated with changes in barrier function. Conclusions: The results of this study provide insight into how specific taxa influence gut barrier integrity and function. More generally, these data in the context of recent published studies makes a significant contribution to our understanding of host-microbe interactions providing new knowledge that can be harnessed by us and others in future mechanistic studies. [ABSTRACT FROM AUTHOR]