Enterocolic increase of cannabinoid receptor type 1 and type 2 and clinical improvement after probiotic administration in dogs with chronic signs of colonic dysmotility without mucosal inflammatory changes.

BACKGROUND: Colonic dysmotility in dogs can cause different GI signs. Sometimes, histology of enterocolic biopsies does not reveal inflammatory infiltrates or mucosal lesions that are typically associated with clinical disease activity. It is speculated that, similarly to humans, colonic dysmotility may be anxiety-based, although recent data demonstrate that irritable bowel syndrome (IBS) could result from acute infectious enteritis. Specific Lactobacillus spp. strains administered orally in humans induced the expression of µ-opioid and cannabinoid receptors in mucosal enterocytes, modulating intestinal morphine-like analgesic functions. We investigated the potential association of GI signs caused by colonic dysmotility and mucosal expression of cannabinoid receptors in intestinal epithelial cells and the number of mucosal mast cells. METHODS: Ten to 15 endoscopic biopsies were collected from colonic mucosa of 20 dogs diagnosed with dysmotility disturbances before and after probiotic (Slab51 bacterial blend; Sivoy® ) administration (3-month period). Number and distribution of mast cells (MCs), and cannabinoid receptor type 1 (CB1) and type 2 (CB2) were evaluated by immunohistochemistry and PCR. Results were compared to data obtained from five clinically healthy dogs (archive samples). KEY RESULTS: Decreased numbers of MCs (P < .0001) and increased CB1- and CB2-positive epithelial cells (P < .0001) in diseased dogs were positively associated with post-treatment CCECAI scores (P < .0001). CONCLUSIONS AND INFERENCES: Our results suggest that probiotic administration can reduce signs of colonic dysmotility, possibly due to microbiota modulation and epithelial cell receptor-mediated signaling in intestinal mucosa.

Gut microbiota manipulation through probiotics oral administration restores glucose homeostasis in a mouse model of Alzheimer's disease.

Cerebral glucose homeostasis deregulation has a role in the pathogenesis and the progression of Alzheimer's disease (AD). Current therapies delay symptoms without definitively curing AD. We have previously shown that probiotics counteract AD progression in 3xTg-AD mice modifying gut microbiota and inducing energy metabolism and glycolysis-gluconeogenesis. Ameliorated cognition is based on higher neuroprotective gut hormones concentrations, reduced amyloid-ß burden, and restored proteolytic pathways. Here, we demonstrate that probiotics oral administration improves glucose uptake in 3xTg-AD mice by restoring the brain expression levels of key glucose transporters (GLUT3, GLUT1) and insulin-like growth factor receptor ß, in accordance with the diminished phosphorylation of adenosine monophosphate-activated protein kinase and protein-kinase B (Akt). In parallel, phosphorylated tau aggregates decrease in treated mice. Probiotics counteract the time-dependent increase of glycated hemoglobin and the accumulation of advanced glycation end products in AD mice, consistently with memory improvement. Collectively, our data elucidate the mechanism through which gut microbiota manipulation ameliorates impaired glucose metabolism in AD, finally delaying the disease progression.

SLAB51 Probiotic Formulation Activates SIRT1 Pathway Promoting Antioxidant and Neuroprotective Effects in an AD Mouse Model.

The gut-brain axis is a bidirectional communication network functionally linking the gut and the central nervous system (CNS). Based on this, the rational manipulation of intestinal microbiota represents a novel attractive therapeutic strategy for the treatment of CNS-associated disorders. In this study, we explored the properties of a probiotic formulation (namely SLAB51) in counteracting brain oxidative damages associated with Alzheimer's disease (AD). Specifically, transgenic AD mice (3xTg-AD) were treated with SLAB51 and the effects on protein oxidation, neuronal antioxidant defence and repair systems were monitored, with the particular focus on the role of SIRT1-related pathways. We demonstrated that SLAB51 markedly reduced oxidative stress in AD mice brain by activating SIRT1-dependent mechanisms, thus representing a promising therapeutic adjuvant in AD treatment.

Probiotic supplementation promotes a reduction in T-cell activation, an increase in Th17 frequencies, and a recovery of intestinal epithelium integrity and mitochondrial morphology in ART-treated HIV-1-positive patients.

INTRODUCTION: HIV infection is characterized by a persistent immune activation associated to a compromised gut barrier immunity and alterations in the profile of the fecal flora linked with the progression of inflammatory symptoms. The effects of high concentration multistrain probiotic (Vivomixx®, Viale del Policlinico 155, Rome, Italy in EU; Visbiome®, Dupont, Madison, Wisconsin in USA) on several aspects of intestinal immunity in ART-experienced HIV-1 patients was evaluated. METHODS: A sub-study of a longitudinal pilot study was performed in HIV-1 patients who received the probiotic supplement twice a day for 6 months (T6). T-cell activation and CD4+ and CD8+ T-cell subsets expressing IFNγ (Th1, Tc1) or IL-17A (Th17, Tc17) were stained by cytoflorimetric analysis. Histological and immunohistochemical analyses were performed on intestinal biopsies while enterocytes apoptosis index was determined by TUNEL assay. RESULTS: A reduction in the frequencies of CD4+ and CD8+ T-cell subsets, expressing CD38+ , HLA-DR+ , or both, and an increase in the percentage of Th17 cell subsets, especially those with central or effector memory phenotype, was recorded in the peripheral blood and in gut-associated lymphoid tissue (GALT) after probiotic intervention. Conversely, Tc1 and Tc17 levels remained substantially unchanged at T6, while Th1 cell subsets increase in the GALT. Probiotic supplementation was also associated to a recovery of the integrity of the gut epithelial barrier, a reduction of both intraepithelial lymphocytes density and enterocyte apoptosis and, an improvement of mitochondrial morphology sustained in part by a modulation of heat shock protein 60. CONCLUSIONS: These findings highlight the potential beneficial effects of probiotic supplementation for the reconstitution of physical and immunological integrity of the mucosal intestinal barrier in ART-treated HIV-1-positive patients.

Microbiota modulation counteracts Alzheimer's disease progression influencing neuronal proteolysis and gut hormones plasma levels.

Gut microbiota has a proven role in regulating multiple neuro-chemical pathways through the highly interconnected gut-brain axis. Oral bacteriotherapy thus has potential in the treatment of central nervous system-related pathologies, such as Alzheimer's disease (AD). Current AD treatments aim to prevent onset, delay progression and ameliorate symptoms. In this work, 3xTg-AD mice in the early stage of AD were treated with SLAB51 probiotic formulation, thereby affecting the composition of gut microbiota and its metabolites. This influenced plasma concentration of inflammatory cytokines and key metabolic hormones considered therapeutic targets in neurodegeneration. Treated mice showed partial restoration of two impaired neuronal proteolytic pathways (the ubiquitin proteasome system and autophagy). Their cognitive decline was decreased compared with controls, due to a reduction in brain damage and reduced accumulation of amyloid beta aggregates. Collectively, our results clearly prove that modulation of the microbiota induces positive effects on neuronal pathways that are able to slow down the progression of Alzheimer's disease.