Can the Therapeutic Spectrum of Probiotics be Extended: Exploring Potential of Gut Microbiome.

Natural therapeutic microorganisms provide a potent alternative healthcare treatment nowadays, with the potential to prevent several human diseases. These health-boosting living organisms, probiotics mostly belong to Gram-positive bacteria such as Lactobacillus, Bifidobacterium, Streptococcus, Saccharomyces, Bacillus and Enterococcus. Initiated almost a century ago, the probiotic application has come a long way. The present review is focused on the potential therapeutic role of probiotics in ameliorating multiple infections, such as upper respiratory tract infections and viral respiratory infections, including COVID-19; liver diseases and hepatic encephalopathy; neurological and psychiatric disorders; autoimmune diseases, particularly rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. Apart from these, the therapeutic exacerbations of probiotics in urinary tract infections have been extremely promising, and several approaches are reviewed and presented here. We also present upcoming and new thrust areas where probiotic therapeutic interventions are showing promising results, like faecal microbial transplant and vaginal microbial transplant.

Gut microbiome and human health: Exploring how the probiotic genus Lactobacillus modulate immune responses.

The highest density of microbes resides in human gastrointestinal tract, known as "Gut microbiome". Of note, the members of the genus Lactobacillus that belong to phyla Firmicutes are the most important probiotic bacteria of the gut microbiome. These gut-residing Lactobacillus species not only communicate with each other but also with the gut epithelial lining to balance the gut barrier integrity, mucosal barrier defence and ameliorate the host immune responses. The human body suffers from several inflammatory diseases affecting the gut, lungs, heart, bone or neural tissues. Mounting evidence supports the significant role of Lactobacillus spp. and their components (such as metabolites, peptidoglycans, and/or surface proteins) in modulatingimmune responses, primarily through exchange of immunological signals between gastrointestinal tract and distant organs. This bidirectional crosstalk which is mediated by Lactobacillus spp. promotes anti-inflammatory response, thereby supporting the improvement of symptoms pertaining to asthma, chronic obstructive pulmonary disease (COPD), neuroinflammatory diseases (such as multiple sclerosis, alzheimer's disease, parkinson's disease), cardiovascular diseases, inflammatory bowel disease (IBD) and chronic infections in patients. The metabolic disorders, obesity and diabetes are characterized by a low-grade inflammation. Genus Lactobacillus alleviates metabolic disorders by regulating the oxidative stress response and inflammatory pathways. Osteoporosis is also associated with bone inflammation and resorption. The Lactobacillus spp. and their metabolites act as powerful immune cell controllers and exhibit a regulatory role in bone resorption and formation, supporting bone health. Thus, this review demonstrated the mechanisms and summarized the evidence of the benefit of Lactobacillus spp. in alleviating inflammatory diseases pertaining to different organs from animal and clinical trials. The present narrative review explores in detail the complex interactions between the gut-dwelling Lactobacillus spp. and the immune components in distant organs to promote host's health.

Possible role of gut microbes and host's immune response in gut-lung homeostasis.

The vast diversity of microbial communities reside in various locations of the human body, and they are collectively named as the 'Human Microbiota.' The majority of those microbes are found in the gastrointestinal and respiratory tracts. The microorganisms present in the gastrointestinal and the respiratory tracts are called the gut microbiota and the airway microbiota, respectively. These microbial communities are known to affect both the metabolic functions and the immune responses of the host. Among multiple factors determining the composition of gut microbiota, diet has played a pivotal role. The gut microbes possess enzymatic machinery for assimilating dietary fibers and releasing different metabolites, primarily short-chain fatty acids (SCFAs). The SCFAs modulate the immune responses of not only the gut but other distal mucosal sites as well, such as the lungs. Dysbiosis in normal gut flora is one of the factors involved in the development of asthma and other respiratory disorders. Of note, several human and murine studies have indicated significant cross-talk between gut microbiota and lung immunity, known as the gut-lung axis. Here, in this review, we summarize the recent state of the field concerning the effect of dietary metabolites, particularly SCFAs, on the "gut-lung axis" as well as discuss its impact on lung health. Moreover, we have highlighted the role of the "gut-lung axis" in SARS-CoV-2 mediated inflammation. Also, to analyze the global research progress on the gut-lung axis and to identify the knowledge gap in this field, we have also utilized the bibliographic tools Dimension database and VOS viewer analysis software. Through network mapping and visualization analysis, we can predict the present research trend and the possibility to explore new directions.

Selection of Potential Probiotic Bacteria from Exclusively Breastfed Infant Faeces with Antagonistic Activity Against Multidrug-Resistant ESKAPE Pathogens.

The past decade has brought a significant rise in antimicrobial resistance, and the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) have considerably aggravated a threat to public health, causing nosocomial infections worldwide. The objective of the current study was to isolate novel probiotic strain with antimicrobial activity against multidrug-resistant ESKAPE pathogens. For this purpose, eighteen breastfed infant faeces were collected and lactic acid bacteria (LAB) with antagonistic activity were isolated. Out of 102 anaerobic LAB isolated, only nine exhibited inhibitory activity against all ESKAPE pathogens. These selected nine isolates were further characterized for their probiotic attributes such as lysozyme tolerance, simulated gastrointestinal tolerance, cellular auto-aggregation and cell surface hydrophobicity. Bile salt deconjugation and cholesterol-lowering capacity was also determined. Among all nine, isolate LBM220 was found to possess superior probiotic potential. Confirmatory identification of isolate LBM220 was done by both 16S rRNA sequence analysis and mass spectrometric analysis using MALDI-TOF. Based on BLAST result, isolate LBM220 was identified as Lactobacillus gasseri. Phylogenetic analysis of Lactobacillus gasseri LBM220 [accession number MN097539] was performed. Also, detailed safety evaluation study of Lact. gasseri LBM220 showed the presence of intrinsic antibiotic resistance and the absence of hemolytic, DNase, gelatinase and toxic mucinolytic activity. Time kill assay was also performed to confirm the strong kill effect of Lact. gasseri LBM220 on all six multidrug resistant ESKAPE pathogens. Thus, Lact. gasseri LBM220 can be utilized and explored as potential probiotic with therapeutic intervention.

In Vitro Evaluation of Probiotic Potential and Safety Assessment of Lactobacillus mucosae Strains Isolated from Donkey's Lactation.

The study, for the first time, reports the efficacy, safety and probiotic properties of two Lactobacillus mucosae strains, Lact. mucosae SRV5 and Lact. mucosae SRV10 isolated from donkey milk. All major in vitro screening assays were employed to evaluate studied strains. Both strains displayed good survivability at gastric pH 2.0, 0.3% bile and simulated oro-gastrointestinal fluid (above 88%). Also, cultures demonstrated good cell surface hydrophobicity and auto-aggregation ability, clearly indicating their effective cell adhesion ability. Furthermore, functional attributes for both strains demonstrated their efficient bile salt hydrolase and cholesterol-reducing ability in spent broth. In addition to this, both strains expressed significant DPPH-radical scavenging ability of both culture supernatant and intact cells. Another auxiliary health benefit exhibited by both these strains is their antimicrobial potential against 18 enteric and 5 multidrug-resistant clinical pathogens with significant inhibition zone size. Extracellular enzyme production such as lipase, amylase, protease and esterase was also studied. Detailed safety evaluation study showed the presence of innate antibiotic resistance and absence of haemolysis, DNAse and gelatinase activity in both the strains. Also, none of the strains possessed toxic mucinolytic activity in mucin degradation assay. To conclude, both donkey milk isolates, Lact. mucosae SRV5[Accession number: MK990014] and Lact. mucosae SRV10 [Accession number: MN064860], exhibited excellent probiotic ability with tolerance to simulated oro-gastrointestinal fluids, cellular hydrophobicity, auto-aggregation, bile salt hydrolase, cholesterol reduction, high antioxidant activity and antimicrobial potential especially against multidrug-resistant pathogens.