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

Functional and morphological adaptations of the digestive system induced by domestication in cats.

Several studies have showed the macroscopic difference in the gastrointestinal tract between the European wildcat (Felis silvestris silvestris) and the domestic cat (Felis silvestris catus). Digestive system in the wildcat is shorter than in domestic species and this feature is considered distinctive in the taxonomic classification of subjects (Schauenberg et al. 1977). This study is a part of a large investigation regarding the microscopic anatomy of the gastrointestinal tract of European wildcat, associated to the study of intestinal microbiome. Its main purpose was to enhance knowledge about this species, to get a comparison with domestic cat, and to evaluate if and how domestication has influenced the functional and morphological development of this apparatus, also n n t ut\u2018s m roflor To this aim we collected, weighted and measured the gastrointestinal tract of twenty European wildcats. Afterwards, intestinal sections were sampled, treated and observed at the microscope in order to evaluate histological characteristics as the villi height and width, crypts depth and wall thickness. Moreover, we wanted to study the intestinal production of an apolipoprotein that is believed directly related to the development of hepatic steatosis, decreasing the amount of lipids deposited in the liver. For this purpose, liver specimens were collected and treated to study histologically the degree of vacuolar degeneration of hepatocytes. Data were analyzed and compared with those of the domestic cats coming from our database. In attempt to evaluate the microbiome, feces and rectal ampulla were collected and sent to the Texas A&M University for pyrosequencing analysis (data not shown). Results demonstrated significant differences in intestinal structure between F. catus and F. s. silvestris. Villi coming from domestic cats were significantly shorter (p<0.0001) and wider (p<0.0142) than in wildcats that showed crypts deeper (p<0.0009). Domestication has led to significant changes in adaptation regarding both behavior and diet. Several studies showed the correlation between diet changes (protein, carbohydrates, and fiber concentration) and morphological adaptation in the gut of different species (Altmann, 1972; Hampson, 1983; Goodlad et al., 1988; Pluske et al., 1996; Sritiawthai et al., 2013). Moreover, data from liver study showed that domestic cat has higher levels of apolipoprotein compared to the wild cat and that the percentage of lipids in the liver was lower in F. catus than in F. s. silvestris. Despite these results, the liver of domestic cat revealed a rate of steatosis higher than in wild cat. Indeed, this pathology proved to be almost absent in wild cats and can be explained by the different nature of the two species diet and microbiome composition. This study revealed that transition from a strictly-carnivorous diet (typical of the wild cat) to an omnivorous type, has modified the nutritional intake considerably and influenced the evolution of the digestive apparatus in domestic cat

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

Th1 paradigm: redirect the cell-mediated immune response in a typical Th2 disease such as Leishmaniasis

Many diseases are the result of the Th2-phenotype immune response directed against an antigen, by triggering an immune-complex disease. In this situation, the manifestation of disease is not closely related to the pathogen, but to an inappropriate host immune response. Leishmaniasis is one of the most classic examples. We investigated the possibility of clinical recovery in dogs with Leishmaniasis following stimulation of the Th1-type immune response. The immunomodulation was based on the exaltation of cell-mediated immune response, by extract of Mycobacteria, ..

A new way of delivering probiotic bacteria in a murine model

Introduction: Health-promoting benefits of probiotics have been demonstrated in gastrointestinal domain after oral administration. Evidences show that probiotics communicate with the host by modulating key signaling pathways in gastrointestinal lymphoid associated tissue (G.A.L.T.). In order to understand how probiotic agents act within deep respirator y tract, we have developed a mouse model of respirator y deliver y, in attempt to examine the effects of Lactobacillus brevis (strain Cd2 Dsm 11988) administration in the pulmonary environment, in terms of host responses, survival rate, modifications of resident microbiota, gross- and histological modifications. Materials and Methods: Thirty CD1-male mice were exposed daily, to different dosage of aerosolised Lactobacillus brevis, for five days. After treatment, mice were euthanised and airways, lungs and bronchoalveolar lavage fluid (B.A.L.F.) were collected and processed for histopathological studies, and microbiota analysis. We analysed mucosal modification and cell response in lungs through histological and immunohistochemical evaluations, using several antibodies to immunophenotyping the immunitar y response. Results: Respirator y deliver y of probiotic bacteria was well tolerated in mice, resulting in mild to absent inflammator y reaction in airways mucosa and lung’s parenchyma. A considerable hyperplasia of the bronchial-associated lymphoid tissue (B.A.L.T.) and an increased number of pulmonar y intravascular and alveolar macrophages was also documented. Analysis of microbioma showed an interesting modulation of respirator y tract-resident bacterial populations. Discussion (and/or Conclusions): Our newly murine model of probiotic deliver y may be useful in attempt to positively modulate the airways/lung response to different pathogens. Our results suggest that probiotic can be used as a novel therapeutic or preventative strategy to manage respirator y diseases