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.

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.Electronic supplementary materialThe online version of this article (10.1007/s12035-018-0973-4) contains supplementary material, which is available to authorized users.

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Alzheimer's disease (AD) is a progressive neurodegeneration characterized by neuron death ending in memory and cognitive decline. A major concern in AD research is the identification of new therapeutics that could prevent or delay the onset of the disorder, with current treatments being effective only in reducing symptoms. In this perspective, the use of engineered probiotics as therapeutic tools for the delivery of molecules to eukaryotic cells is finding application in several disorders. This work introduces a new strategy for AD treatment based on the use of a Lactobacillus lactis strain carrying one plasmid (pExu) that contains a eukaryotic expression cassette encoding the human p62 protein. 3xTg-AD mice orally administered with these bacteria for two months showed an increased expression of endogenous p62 in the brain, with a protein delivery mechanism involving both lymphatic vessels and neural terminations, and positive effects on the major AD hallmarks. Mice showed ameliorated memory, modulation of the ubiquitin-proteasome system and autophagy, reduced levels of amyloid peptides, and diminished neuronal oxidative and inflammatory processes. Globally, we demonstrate that these extremely safe, non-pathogenic and non-invasive bacteria used as delivery vehicles for the p62 protein represent an innovative and realistic therapeutic approach in AD.

Chronic constipation (CC) and idiopathic megacolon (IMC) occur frequently in cats. The aim of the study was to investigate the effects of a multi-strain probiotic (SLAB51™) in constipated cats (n=7) and in patients with megacolon and constipation (n=3). Ten pet cats with a diagnosis of chronic constipation, non-responsive to medical management received orally 2×10 bacteria daily for 90 days. For microbiota analysis, selected bacterial groups were analysed by qPCR. Histological samples in megacolons were evaluated for interstitial cells of Cajal (ICC), enteric neurons, and neuronal apoptosis. Biopsies were compared at baseline (T0) and after the end of treatment (T1), and with those obtained from healthy control tissues (archived material from five healthy cats). Constipated cats displayed significantly lower ICC, and cats with idiopathic megacolon had significantly more apoptotic enteric neurons than controls. After treatment with SLAB51™, significant decreases were observed for feline chronic enteropathy activity index (FCEAI) (P=0.006), faecal consistency score, and mucosal histology scores (P<0.001). In contrast, a significant increase of ICC was observed after probiotic therapy. Lactobacillus spp. and Bacteroidetes were increased significantly after treatment (comparing constipated cats before and after treatment, and control healthy cats to constipated cats after treatment), but no other differences in microbiota were found between healthy controls and constipated cats. Treatment with SLAB51™ in cats with chronic constipation and idiopathic megacolon showed significant clinical improvement after treatment, and histological parameters suggest a potential anti-inflammatory effect of SLAB51™, associated with a reduction of mucosal infiltration, and restoration of the number of interstitial cells of Cajal.

Shigella spp. are pathogenic bacteria that cause bacillary dysentery in humans by invading the colonic and rectal mucosa where they induce dramatic inflammation. Here, we have analyzed the role of the soluble PRR Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity. Mice that had been intranasally infected with S. flexneri were rescued from death by treatment with recombinant PTX3. In vitro PTX3 exerts the antibacterial activity against Shigella, impairing epithelial cell invasion and contributing to the bactericidal activity of serum.PTX3 is produced upon LPS-TLR4 stimulation in accordance with the lipid A structure of Shigella. In the plasma of infected patients, the level of PTX3 amount only correlates strongly with symptom severity. These results signal PTX3 as a novel player in Shigella pathogenesis and its potential role in fighting shigellosis. Finally, we suggest that the plasma level of PTX3 in shigellosis patients could act as a biomarker for infection severity.

BackgroundColonic 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.MethodsTen 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 resultsDecreased 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 inferencesOur 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.