Membrane Vesicles Derived from Gut Microbiota and Probiotics: Cutting-Edge Therapeutic Approaches for Multidrug-Resistant Superbugs Linked to Neurological Anomalies

Abstract

Multidrug-resistant (MDR) superbugs can breach the blood–brain barrier (BBB), leading to a continuous barrage of pro-inflammatory modulators and induction of severe infection-related pathologies, including meningitis and brain abscess. Both broad-spectrum or species-specific antibiotics (β-lactamase inhibitors, polymyxins, vancomycin, meropenem, plazomicin, and sarecycline) and biocompatible poly (lactic-co-glycolic acid) (PLGA) nanoparticles have been used to treat these infections. However, new therapeutic platforms with a broad impact that do not exert off-target deleterious effects are needed. Membrane vesicles or extracellular vesicles (EVs) are lipid bilayer-enclosed particles with therapeutic potential owing to their ability to circumvent BBB constraints. Bacteria-derived EVs (bEVs) from gut microbiota are efficient transporters that can penetrate the central nervous system. In fact, bEVs can be remodeled via surface modification and CRISPR/Cas editing and, thus, represent a novel platform for conferring protection against infections breaching the BBB. Here, we discuss the latest scientific research related to gut microbiota- and probiotic-derived bEVs, and their therapeutic modifications, in terms of regulating neurotransmitters and inhibiting quorum sensing, for the treatment of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases. We also emphasize the benefits of probiotic-derived bEVs to human health and propose a novel direction for the development of innovative heterologous expression systems to combat BBB-crossing pathogens.

Bio-Inspired Drug Delivery Systems: From Synthetic Polypeptide Vesicles to Outer Membrane Vesicles

“…Different from artificially assembled polypeptide vesicles, vesicles derived from the outer membrane of Gram-negative bacteria are called OMVs [ 17 , 18 , 19 , 20 ]. OMVs are widely produced, vary in size and composition, and contain soluble periplasmic content.…”

Lactic Acid Bacteria (LAB) and Neuroprotection, What Is New? An Up-To-Date Systematic Review

“…Extracellular vesicles (EVs), also known as membrane vesicles, are lipid-bilayer-enclosed particles with potential therapeutic use [ 80 ]. EVs produced by bacteria, notably LAB, are used in intercellular communication between the microbiota and the host.…”

Extracellular Vesicles of Probiotics: Shedding Light on the Biological Activity and Future Applications

“…Taking into account their biological properties, probiotic EVs could also be used for the treatment of certain neurological diseases. In fact, having the potential to cross the blood–brain barrier, they could represent efficient transporters for the delivery of drugs into the central nervous system [ 11 ]. Yuan et al [ 149 ] and Sun et al [ 150 ] extensively reported in their reviews the potential application of EVs-based strategies in the treatment of neurological disorders.…”

“…Although probiotics are currently in the center of interest of pharmaceutical concerns, more and more research focuses on searching for alternatives to these classically used products [ 8 , 9 ]. Difficulties in maintaining the viability of probiotics in commercial products and the fact that the viability of these microorganisms is not always necessary to obtain therapeutic effects have led to the concept of postbiotics [ 5 , 7 , 10 , 11 ]. Postbiotics are a mixture of metabolic products or non-viable fragments of probiotics that have a beneficial effect on the functioning of the human body [ 8 , 12 ].…”

“…Despite the fact that research on postbiotics is still in its infancy, a number of health-promoting properties of these new products have already been demonstrated (maintenance of the proper structure of the resident microbiota, strengthening the host epithelial barrier, modulation of the local and systemic immune response, or increase of the host metabolic activity) [ 12 ]. As non-viable elements of probiotics, postbiotics present their strictly defined technological properties and thus represent a promising tool for obtaining therapeutic effects [ 10 , 11 , 13 ]. These parameters include a favorable level of absorption and distribution of postbiotics [ 13 ] and the lack of risk to spread resistance mechanisms, as documented between probiotics and microbiota or pathogens [ 12 ].…”