Lacticaseibacillus rhamnosus-Derived Exopolysaccharide Attenuates D-Galactose-Induced Oxidative Stress and Inflammatory Brain Injury and Modulates Gut Microbiota in a Mouse Model.

This study aimed to investigate the protective effect of a novel exopolysaccharide EPSRam12, produced by Lacticaseibacillus rhamnosus Ram12, against D-galactose-induced brain injury and gut microbiota dysbiosis in mice. The findings demonstrate that EPSRam12 increases the level of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, total antioxidant capacity, and the level of anti-inflammatory cytokine IL-10, while decreasing malonaldehyde, nitric oxide, pro-inflammatory cytokines including TNF-α, IL-1ß, IL-6, MCP-1, and the mRNA expression of cyclooxygenase-2, inducible nitric oxide synthase, and the activation of nuclear factor-kappa-B in the brain tissues of D-galactose-treated mice. Further analyses reveal that EPSRam12 improves gut mucosal barrier function and increases the levels of short-chain fatty acids (SCFAs) in the intestine while restoring gut microbial diversity by enriching the abundance of SCFA-producing microbial genera Prevotella, Clostridium, Intestinimonas, and Acetatifactor while decreasing potential pathobionts including Helicobacter. These findings of antioxidative and anti-inflammatory effects in the brain and ameliorative effects on epithelial integrity, SCFAs and microbiota in the gut, provide novel insights into the effect of EPSRam12 intervention on the gut-microbiome-brain axis and should facilitate prospective understanding of microbial exopolysaccharide for improved host health.

Antioxidant and immunomodulatory potency of Lacticaseibacillus rhamnosus NCDC24 fermented milk-derived peptides: A computationally guided in-vitro and ex-vivo investigation.

Infections of microbial and non-microbial origins have been associated with significant immunological manifestations, thereby underscoring the need for a thorough understanding and investigation of novel immunomodulatory and antioxidant molecules that could prevent these incidences. To this end, we herein aim to identify fermented milk peptides with antioxidant and immunomodulatory properties that could be exploited for specific future applications. Our computational prediction models indicate that these peptides are non-toxic and possess considerable hydrophobicity (19.82-38.96 %) and functionality. Further analyses reveal that two of the four peptides, i.e., Pep 1 (AGWNIPM) and Pep 4 (YLGYLEQLLR), possess higher in-vitro antioxidant activity. The immunomodulatory potential of these two peptides (Pep 1 and Pep 4) is further demonstrated by using a combination of molecular simulation trajectory and ex-vivo approaches. Both peptides demonstrate ability to control the production of pro- inflammatory (TNF-α, IL-1, and IL-6) and anti-inflammatory (IL-10) cytokines as well as nitric oxide release in LPS-stimulated murine peritoneal macrophages. Similarly, peptide interferences also lead to significant (P < 0.05) improvement in macrophage phagocytic capacity. Taken together, these findings highlight the antioxidant and immunomodulatory properties of fermented milk peptides (Pep 1 and Pep 4) within the cellular environment and should facilitate prospective studies exploring such bioactive peptides and related functional molecules mediating the benefits of fermented milk products on human health.

Fostering next-generation probiotics in human gut by targeted dietary modulation: An emerging perspective.

Emerging evidence and an in-depth understanding of the microbiome have helped in identifying beneficial commensals and their therapeutic potentials. Specific commensal taxa/ strains of the human gut microbiome have been positively associated with human health and recently termed as next-generation probiotics (NGPs). Of these, Akkermansia muciniphila, Ruminococcus bromii, Faecalibacterium prausnitzii, Anaerobutyricum hallii, and Roseburia intestinalis are the five most relevant gut-derived NGPs that have demonstrated therapeutic potential in managing metabolic diseases. Specific and natural dietary interventions can modulate the abundance and activity of these beneficial bacteria in the gut. Hence, the understanding of targeted stimulation of specific NGP by specific probiotic-targeted diets (PTD) is indispensable for the rational application of their combination. The supplementation of NGP with its specific PTD will help the strain(s) to compete with harmful microbes and acquire its niche. This combination would enhance the effectiveness of NGPs to be used as "live biotherapeutic products" or food nutraceuticals. Under the current milieu, we review various PTDs that influence the abundance of specific potential NGPs, and contemplates potential interactions between diet, microbes, and their effects on host health. Taking into account the study mentioned, we propose that combining NGPs will provide an alternate solution for developing the new diet in conjunction with PTD.

Evolutionary concepts in the functional biotics arena: a mini-review.

Over the years, the attempts to elucidate the role of beneficial microorganisms in shaping human health are becoming fairly apparent. The functional impact conferred by such microbes is not only transmitted by viable cells or their metabolites but also through non-viable cells. Extensive research to unveil the protective action of such wonder bugs has resulted in categorizing the beneficial microflora and their bioactive metabolites into a variety of functional biotic concepts based on their intended applications in various forms. In the modern era, these are often termed as probiotics, prebiotics, synbiotics, postbiotics, next-generation probiotics, psychobiotics, oncobiotics, pharmabiotics, and metabiotics. Currently, the concept of traditional probiotics is being widened to include microbes beyond lactic acid bacteria. Indeed, this diversification has broadened the functional food portfolio from food to pharmaceuticals. In this context, the present review aims to summarize the existing biotic concepts and their differences thereof.

Antibiotic Resistance Crisis: An Update on Antagonistic Interactions between Probiotics and Methicillin-Resistant Staphylococcus aureus (MRSA).

Antimicrobial resistance (AMR) havoc is a global multifaceted crisis endowing a significant challenge for the successful eradication of devastating pathogens. Methicillin-Resistant Staphylococcus aureus (MRSA) is an enduring superbug involved in causing devastating infections. Although MRSA is a frequent colonizer of human skin, wound, and anterior nares, the intestinal colonization of MRSA has greatly increased the risk of inducing MRSA-associated colitis besides creating a conducive environment for horizontal transfer of resistant genes to commensal microbes. On the other hand, staphylococcal resistance to last-resort antibiotics has urged the development of novel antimicrobial agents for the effective decolonization of MRSA. In response, probiotics and their metabolites (postbiotics) have been proposed as the adjunct therapeutic avenues. Probiotics exhibit a multitude of anti-MRSA actions (anti-bacterial, anti-biofilm, anti-virulence, anti-drug resistance, co-aggregation, and anti-quorum sensing) through the production of numerous antagonistic compounds such as organic acids, hydrogen peroxide, low molecular weight compounds, biosurfactants, bacteriocins, and bacteriocins like inhibitory substances. Besides, probiotics stabilize the epithelial barrier function and positively modulate the host immune system via regulating various signal transduction mechanisms. Preclinical and human intervention studies have suggested that probiotics outcompete with MRSA by exhibiting anti-colonization mechanisms via protective, competitive, and displacement mode. In this review, we aim to highlight the dynamics of MRSA associated virulence and drug resistance properties, and how probiotics antagonize MRSA through various mechanism of action.

Postbiotics-parabiotics: the new horizons in microbial biotherapy and functional foods.

Probiotics have several health benefits by modulating gut microbiome; however, techno-functional limitations such as viability controls have hampered their full potential applications in the food and pharmaceutical sectors. Therefore, the focus is gradually shifting from viable probiotic bacteria towards non-viable paraprobiotics and/or probiotics derived biomolecules, so-called postbiotics. Paraprobiotics and postbiotics are the emerging concepts in the functional foods field because they impart an array of health-promoting properties. Although, these terms are not well defined, however, for time being these terms have been defined as here. The postbiotics are the complex mixture of metabolic products secreted by probiotics in cell-free supernatants such as enzymes, secreted proteins, short chain fatty acids, vitamins, secreted biosurfactants, amino acids, peptides, organic acids, etc. While, the paraprobiotics are the inactivated microbial cells of probiotics (intact or ruptured containing cell components such as peptidoglycans, teichoic acids, surface proteins, etc.) or crude cell extracts (i.e. with complex chemical composition)". However, in many instances postbiotics have been used for whole category of postbiotics and parabiotics. These elicit several advantages over probiotics like; (i) availability in their pure form, (ii) ease in production and storage, (iii) availability of production process for industrial-scale-up, (iv) specific mechanism of action, (v) better accessibility of Microbes Associated Molecular Pattern (MAMP) during recognition and interaction with Pattern Recognition Receptors (PRR) and (vi) more likely to trigger only the targeted responses by specific ligand-receptor interactions. The current review comprehensively summarizes and discussed various methodologies implied to extract, purify, and identification of paraprobiotic and postbiotic compounds and their potential health benefits.