A novel synbiotic delays Alzheimer's disease onset via combinatorial gut-brain-axis signaling in Drosophila melanogaster.

The gut-brain-axis (GBA) describing the bidirectional communication between the gut microbiota and brain was recently implicated in Alzheimer's disease (AD). The current study describes a novel synbiotic containing three metabolically active probiotics and a novel polyphenol-rich prebiotic which has beneficial impacts on the onset and progression of AD. In a transgenic humanized Drosophila melanogaster model of AD, the synbiotic increased survivability and motility and rescued amyloid beta deposition and acetylcholinesterase activity. Such drastic effects were due to the synbiotic's combinatorial action on GBA signaling pathways including metabolic stability, immune signaling, oxidative and mitochondrial stress possibly through pathways implicating PPARγ. Overall, this study shows that the therapeutic potential of GBA signaling is best harnessed in a synbiotic that simultaneously targets multiple risk factors of AD.

Ferulic Acid Produced by Lactobacillus fermentum Influences Developmental Growth Through a dTOR-Mediated Mechanism.

The composition and activity of the gut microbiota impacts several energy-regulating conditions including diabetes, obesity and metabolic syndrome; however, the specific mechanisms linking the gut microbiota with the host's energy homeostasis remain elusive. Probiotics are health-promoting bacteria that when consumed, alter the composition and/or metabolism of resident microbiota conferring health benefits. To assess the role of a specific probiotic treatment on microbiota-derived impacts on energy homeostasis in the context of development, Drosophila melanogaster larvae were orally administered the probiotic Lactobacillus fermentum NCIMB 5221 or its metabolic product, ferulic acid: a potent anti-inflammatory and anti-oxidant hydroxycinnamic acid. In Drosophila larvae, both the probiotic and metabolite treatments advanced the nutritionally dependent stages of development in a dose-dependent manner while not affecting the hormonally controlled pupariation stage. These treatments correspondingly accelerated the developmental phase-dependent 20-hydroxyecdysone and insulin receptor gene expression surges and altered the phasic expression of downstream insulin signalling factors including dAkt, dTOR and dFOXO indicating a deep level of nutritionally dependent regulatory control. Administering Drosophila both ferulic acid and the TOR inhibitor rapamycin eliminated the physiological and molecular developmental advances indicating that microbial ferulic acid affects energy utilization in a dTOR-dependent manner outlining a potential mechanism of action of L. fermentum NCIMB 5221 on modulating microbiota dynamics to modulate energy homeostasis. TOR conservation from flies to humans indicates that probiotic therapy with L. fermentum NCIMB 5221 has a high therapeutic potential towards several human energy regulatory diseases such as obesity, diabetes and cancer.

A novel polyphenolic prebiotic and probiotic formulation have synergistic effects on the gut microbiota influencing Drosophila melanogaster physiology.

The gut microbiota is a vast community of synergistic bacterial species providing health benefits to the host. Imbalances in the gut microbiota (dysbiosis) due to diet, antibiotic use, age and stress contribute to disease development including diabetes, obesity, colon cancer, inflammatory bowel disease, inflammaging and neurodegeneration. Fortunately, a probiotic regime with a diet rich in prebiotics may reverse dysbiosis promoting health and wellness in age. The current study designs, optimizes and tests a novel probiotic and synbiotic formulation consisting of three metabolically active probiotics Lactobacillus plantarum, Lactobacillus fermentum and Bifidobacteria infantis together with a novel polyphenol-rich prebiotic, Triphala. The prebiotic action of Triphala was characterized using in vitro batch cultures, Drosophila melanogaster and a simulated model of the human gastrointestinal tract (SHIME) where in each model, Triphala supported growth of beneficial bacteria while inhibiting pathogenic species. Neither Triphala at 0.5% w/v nor the individual probiotics at 5.0 × 108 to 7.5 × 109 CFU/ml demonstrated toxicity in Drosophila. Interestingly, motility was combinatorially enhanced by the probiotic and synbiotic formulations reflecting the beneficial variations in the gut microbiota. Altogether, the present study shows that probiotics and synbiotics in combination are more effective at modulating the gut microbiota and eliciting biological effects than their components.

Human Serum Albumin Nanoparticles for Use in Cancer Drug Delivery: Process Optimization and In Vitro Characterization.

Human serum albumin nanoparticles (HSA-NPs) are widely-used drug delivery systems with applications in various diseases, like cancer. For intravenous administration of HSA-NPs, the particle size, surface charge, drug loading and in vitro release kinetics are important parameters for consideration. This study focuses on the development of stable HSA-NPs containing the anti-cancer drug paclitaxel (PTX) via the emulsion-solvent evaporation method using a high-pressure homogenizer. The key parameters for the preparation of PTX-HSA-NPs are: the starting concentrations of HSA, PTX and the organic solvent, including the homogenization pressure and its number cycles, were optimized. Results indicate a size of 143.4 ± 0.7 nm and 170.2 ± 1.4 nm with a surface charge of -5.6 ± 0.8 mV and -17.4 ± 0.5 mV for HSA-NPs and PTX-HSA-NPs (0.5 mg/mL of PTX), respectively. The yield of the PTX-HSA-NPs was ~93% with an encapsulation efficiency of ~82%. To investigate the safety and effectiveness of the PTX-HSA-NPs, an in vitro drug release and cytotoxicity assay was performed on human breast cancer cell line (MCF-7). The PTX-HSA-NPs showed dose-dependent toxicity on cells of 52%, 39.3% and 22.6% with increasing concentrations of PTX at 8, 20.2 and 31.4 µg/mL, respectively. In summary, all parameters involved in HSA-NPs' preparation, its anticancer efficacy and scale-up are outlined in this research article.