Search Results (6,464)

The human microbiome, a complex ecosystem of microorganisms residing in and on the body, plays a pivotal role in the regulation of a wide range of physiological processes, including digestion, immune responses, and metabolic functions. In recent years, the rapidly growing field of microbiome-driven therapeutics has garnered significant attention owing to its potential to revolutionize healthcare. This review explores the evolving landscape of microbiome-based therapies, with a particular focus on the gut microbiome and its implications for both gut health and precision medicine. We highlight recent advances in understanding how microbial communities influence disease pathogenesis and treatment outcomes, spanning conditions such as inflammatory bowel disease (IBD), metabolic disorders, neurological diseases, and even cancer. This article also discusses emerging therapeutic strategies, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and microbial-based drugs, as well as the challenges associated with their clinical implementation. Additionally, we examined how the integration of microbiome profiling and metagenomic data is advancing the field of precision medicine, paving the way for personalized and effective treatments. This review serves as a comprehensive resource that synthesizes current knowledge, identifies key gaps in microbiome research, and offers insights into the future direction of microbiome-driven therapeutics, thus providing a valuable framework for clinicians, researchers, and policymakers seeking to harness the potential of microbiomes to advance personalized healthcare solutions. Full article

Irritable bowel syndrome (IBS) is a chronic disorder of the gastrointestinal tract. Its pathogenesis involves multiple factors, including visceral hypersensitivity and immune activation. NLRP3 inflammasome is part of the nucleotide-binding oligomerization domain-like receptor (NLR) family, a crucial component of the innate immune system. Preclinical studies have demonstrated that inhibiting NLRP3 reduces visceral sensitivity and IBS symptoms, like abdominal pain, and diarrhea, suggesting that targeting the NLRP3 might represent a novel therapeutic approach for IBS. This review aims to assess the NLRP3 inhibitors (tranilast, β-hydroxybutyrate, Chang-Kang-fang, paeoniflorin, coptisine, BAY 11-7082, and Bifidobacterium longum), highlighting the signaling pathways, and their potential role in IBS symptoms management was assessed. Although premature, knowledge of the action of synthetic small molecules, phytochemicals, organic compounds, and probiotics might make NLRP3 a new therapeutic target in the quiver of physicians’ therapeutic choices for IBS symptoms management. Full article

Background and Objectives: Periodontal inflammation, often linked to oral microbiota dysbiosis dominated by pathogenic bacteria, remains a significant challenge in periodontitis management. Traditional periodontal therapies primarily reduce the bacterial load but fail to restore the microbiota balance. Probiotics offer a promising therapeutic adjunct with their ability to enhance beneficial bacteria. This study investigates the effects of probiotics on the oral microbiota, inflammatory markers (IL-1β, TNF-α), and clinical parameters (gingival index, bleeding index, and periodontal pocket depth). Materials and Methods: In this pilot study, 80 patients with moderate-to-severe periodontitis were assigned to two groups. Group A received standard periodontal therapy (non-surgical periodontal therapy (NSPT)) with probiotic supplementation (Lactobacillus reuteri, 2 × 10⁹ CFU daily for 8 weeks), and Group B received standard treatment with a placebo. Microbiological changes were assessed via quantitative PCR, while inflammatory markers (IL-1β, TNF-α) were analyzed using ELISA. Clinical parameters, including the gingival index (GI), bleeding index (BI), and periodontal pocket depth (PPD), were measured at baseline (T0), 4 weeks (T1), and 8 weeks (T2) using standardized methods. Results: Probiotic therapy (Group A) significantly reduced the pathogenic bacteria and increased the beneficial bacteria levels compared to the placebo (p < 0.01). Inflammatory markers decreased by 37% (IL-1β) and 42% (TNF-α), while clinical parameters improved, with reductions in the gingival and bleeding indices (−1.5, −1.3) and a 2 mm decrease in the periodontal pocket depth (p < 0.01). Conclusions: Probiotics, as an adjunct to periodontal therapy, effectively restore the microbiota balance, reduce inflammation, and improve clinical outcomes in periodontitis. Full article

Elucidating the gene regulatory mechanisms underlying the gut–brain axis is critical for uncovering novel gut–brain interaction pathways and developing therapeutic strategies for gut bacteria-associated neurological disorders. Most studies have primarily investigated how gut bacteria modulate host epigenetics and gene expression; their impact on host alternative splicing, particularly in the brain, remains largely unexplored. Here, we investigated the effects of the gut-associated probiotic Lacidofil^® on alternative splicing across 10 regions of the rat brain using published RNA-sequencing data. The Lacidofil^® altogether altered 2941 differential splicing events, predominantly, skipped exon (SE) and mutually exclusive exon (MXE) events. Protein–protein interactions and a KEGG analysis of differentially spliced genes (DSGs) revealed consistent enrichment in the spliceosome and vesicle transport complexes, as well as in pathways related to neurodegenerative diseases, synaptic function and plasticity, and substance addiction across brain regions. Using the PsyGeNET platform, we found that DSGs from the locus coeruleus (LConly), medial preoptic area (mPOA), and ventral dentate gyrus (venDG) were enriched in depression-associated or schizophrenia-associated genes. Notably, we highlight the App gene, where Lacidofil^® precisely regulated the splicing of two exons causally involved in amyloid β protein-based neurodegenerative diseases. Although the splicing factors exhibited both splicing plasticity and expression plasticity in response to Lacidofil^®, the overlap between DSGs and differentially expressed genes (DEGs) in most brain regions was rather low. Our study provides novel mechanistic insight into how gut probiotics might influence brain function through the modulation of RNA splicing. Full article

Metabolic disorders, including type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome, are systemic conditions that profoundly impact the skin microbiota, a dynamic community of bacteria, fungi, viruses, and mites essential for cutaneous health. Dysbiosis caused by metabolic dysfunction contributes to skin barrier disruption, immune dysregulation, and increased susceptibility to inflammatory skin diseases, including psoriasis, atopic dermatitis, and acne. For instance, hyperglycemia in T2DM leads to the formation of advanced glycation end products (AGEs), which bind to the receptor for AGEs (RAGE) on keratinocytes and immune cells, promoting oxidative stress and inflammation while facilitating Staphylococcus aureus colonization in atopic dermatitis. Similarly, obesity-induced dysregulation of sebaceous lipid composition increases saturated fatty acids, favoring pathogenic strains of Cutibacterium acnes, which produce inflammatory metabolites that exacerbate acne. Advances in metabolomics and microbiome sequencing have unveiled critical biomarkers, such as short-chain fatty acids and microbial signatures, predictive of therapeutic outcomes. For example, elevated butyrate levels in psoriasis have been associated with reduced Th17-mediated inflammation, while the presence of specific Lactobacillus strains has shown potential to modulate immune tolerance in atopic dermatitis. Furthermore, machine learning models are increasingly used to integrate multi-omics data, enabling personalized interventions. Emerging therapies, such as probiotics and postbiotics, aim to restore microbial diversity, while phage therapy selectively targets pathogenic bacteria like Staphylococcus aureus without disrupting beneficial flora. Clinical trials have demonstrated significant reductions in inflammatory lesions and improved quality-of-life metrics in patients receiving these microbiota-targeted treatments. This review synthesizes current evidence on the bidirectional interplay between metabolic disorders and skin microbiota, highlighting therapeutic implications and future directions. By addressing systemic metabolic dysfunction and microbiota-mediated pathways, precision strategies are paving the way for improved patient outcomes in dermatologic care. Full article

The discovery and application of bacteriocin-producing probiotics, such as Streptococcus salivarius K12 (BLIS K12), represent significant advances in the prevention and management of bacterial infections, particularly in the oral cavity and upper respiratory tract. Originally developed for its bacteriocin-mediated inhibition of the important bacterial pathogen Streptococcus pyogenes, BLIS K12 has more recently also demonstrated potential in the modulation and prevention of viral infections, including COVID-19. Emerging evidence also suggests a broader role for BLIS K12 in immune regulation, with implications for controlling hyperinflammatory responses and enhancing mucosal immunity. Of particular interest is recent work indicating that BLIS K12 can modulate antibody responses against viral antigens, such as the SARS-CoV-2 spike protein, positioning it as a unique adjunct in managing viral infections. This review chronicles the pathway of BLIS K12’s probiotic development, emphasizing its relevant bacteriocin mechanisms, oral health applications, emerging antiviral properties, and potential broader health benefits through immune modulation, all of which position it as a significant non-pharmacological adjunct in managing respiratory and immune health Full article

Lactobacillus is a key genus of probiotics commonly utilized for the treatment of oral infections The primary aim of our research was to investigate the probiotic potential of the newly isolated Levilactobacillus brevis DPL5 strain from human breast milk, focusing on its ability to combat biofilm-forming pathogens such as Staphylococcus aureus. Employing in vitro approaches, we demonstrate L. brevis DPL5′s ability to endure at pH 3 with survival rates above 30%, and withstand the osmotic stress often found during industrial processes like fermentation and freeze drying, retaining over 90% viability. The lyophilized cell-free supernatant of L. brevis DPL5 had a significant antagonistic effect against biofilm-producing nasal strains of Staphylococcus aureus, and it completely eradicated biofilms at subinhibitory concentrations of 20 mg·mL⁻¹. Higher concentrations of 69 mg·mL⁻¹ were found to have a 99% bactericidal effect, based on the conducted probability analysis, indicating the production of bactericidal bioactive extracellular compounds capable of disrupting the biofilm formation of pathogens like S. aureus. Furthermore, genome-wide sequencing and analysis of L. brevis DPL5 with cutting-edge Nanopore technology has uncovered over 50 genes linked to probiotic activity, supporting its ability to adapt and thrive in the harsh gut environment. The genome also contains multiple biosynthetic gene clusters such as lanthipeptide class IV, Type III polyketide synthase (T3PKS), and ribosomally synthesized, and post-translationally modified peptides (RiPP-like compounds), all of which are associated with antibacterial properties. Our study paves the way for the further exploration of DPL5, setting the stage for innovative, nature-inspired solutions to combat stubborn bacterial infections. Full article

Northern Thai culture offers a rich variety of traditional fermented foods beneficial for gastrointestinal health. In this study, we characterized lactic acid bacteria (LAB) from various indigenous fermented foods as potential probiotic candidates and determined their properties for application in commercial synbiotic formulation. Five isolates demonstrating high tolerance to low pH (2.0) and 0.3% bile salts were collected and characterized. These included three strains of Lactiplantibacillus plantarum isolated from nham (NB1, NP2, and NP11) and two strains of Limosilactobacillus fermentum isolated from pla-som (PS4 and PS7). All the selected LAB isolates exhibited γ-hemolytic activity, strong antimicrobial activity, and high resistance to gastric and duodenal digestion conditions. Among the LAB isolates, L. plantarum NB1 demonstrated the highest capacity for adhesion to Caco-2 cells, auto-aggregation, and antioxidant activity, differing significantly (p < 0.05) from the other isolates. Furthermore, the NB1 strain exhibited preferential growth in the presence of commercial prebiotics (fructooligosaccharide, lactose, and inulin) and good survival after lyophilization, which is a desirable characteristic for a powdered ingredient. Therefore, the NB1 strain is a suitable probiotic candidate for applications in synbiotic formulation or as a functional food ingredient. Full article

Probiotics are beneficial to humans and animals and often used for regulating immunity, intestinal microbiota balance, and animal growth performance. Donkey husbandry has boomed in China in recent years and there is an urgent need for probiotics effective for improving donkey health. However, studies on potential probiotic strains isolated from donkeys are scarce. This project aimed to screen LAB strains from donkey feces, detect their antimicrobial activity and evaluate their probiotic characteristics in vitro. Thirteen LAB isolates showed different degrees of antimicrobial activity against four indicator bacteria: three common pathogens (Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium) and one pathogen restricted to equines (Salmonella. abortus equi), eight of which could inhibit all four pathogens. Seven isolates showed higher tolerance to low pH and bile salts, with >50% and >60% survival rates, respectively. Five of them had more than 50% survival rate to artificial gastric and intestinal fluids. Only three isolates possessed good properties, with >40% auto-aggregation, >40% hydrophobicity, and high co-aggregation with the indicator pathogens. An L9 isolate, identified as Ligilactobacillus salivarius, was sensitive to most antibiotics tested. Overall, these results indicate that the L. salivarius L9 isolate meets the requirements of the probiotics selection criteria in vitro and can potentially be developed as a probiotic for donkeys. Full article

Probiotics and their postbiotics have the potential to improve the health and growth performance of piglets, which has brought them widespread attention in the post-antibiotic era. In the present study, the effects of dietary supplementation of Lactobacillus reuteri postbiotics on the growth performance, intestinal flora structure and plasma metabolome of weaned piglets were investigated. A total of 816 healthy male piglets with uniform weight were divided into two treatment groups: piglets in the control (CTR) group were fed with a basic diet, and the ones in the LAC group were fed with the basic diet supplemented with 500 mg/kg Lactobacillus reuteri postbiotics. There were six replicates in each group and 68 piglets in each replicate. The animal trial lasted for 30 days. The feces and blood of piglets were collected for investigation, and the growth performance during the trial was counted. Our outcomes show that dietary supplementation with Lactobacillus reuteri postbiotics had no effect on the growth performance of piglets; however, it reduced the mortality rate of piglets by 6.37%. The levels of total superoxide dismutase in the serum, propionic acid and butyric acid in the feces were elevated, and the content of malondialdehyde in the serum was decreased with Lactobacillus reuteri postbiotics-treated piglets (p < 0.05). The fecal flora sequencing results show that the relative abundance of Firmicutes and monoglobus was upregulated, and the relative abundance of Bacteroides was downregulated with Lactobacillus reuteri postbiotics-treated piglets (p < 0.05). In addition, the levels of propionic acid and butyric acid in the feces were positively correlated with the relative abundance of Firmicutes and negatively correlated with the relative abundance of Bacteroides (p < 0.05). The plasma metabolome results show that dietary supplementation with Lactobacillus reuteri postbiotics raised the level of coenzyme Q10 in the serum, and the abundance of coenzyme Q10 was positively correlated with the relative abundance of Firmicutes and the level of total superoxide dismutase in the serum. In conclusion, dietary supplementation with Lactobacillus reuteri postbiotics contributed to improving the antioxidant function and reducing the mortality of piglets by regulating the structure of intestinal flora and upregulating the content of coenzyme Q10 in serum. Full article

Oral candidiasis is one of the most common infections in the immunocompromised. Biofilms of Candida species can make treatments difficult, leading to oral infection recurrence. This research aimed to isolate a Lactobacillus with anti-Candida effects from the oral cavity. An oral Lactobacillus was isolated in caries-free individuals. The best isolate was evaluated against Candida spp. planktonic and biofilm forms. The bacterial impacts on Candida biofilms’ adhesion to acrylic discs were analyzed through an in vitro test. L. reuteri AJCR4 had the best anti-Candida activity in the preliminary screening. Results were promising in both planktonic and biofilms, particularly with C. albicans SC5314 and C. tropicalis ATCC750, where no viable cells were detected when using the cell-free supernatant (undiluted). In C. glabrata ATCC2001 and C. parapsilosis ATCC22019 biofilms, reductions of 3 Log₁₀ and more than 2 Log₁₀, respectively, were noted when using a cell suspension of L. reuteri ACJR4 (10⁸ CFU/mL). On polymethyl methacrylate acrylic discs, the cell-free supernatant reduced Candida adhesion, resulting in no viable cell detection on the surface. In conclusion, L. reuteri AJCR4 demonstrated notable antifungal activity against Candida biofilms. This oral isolate and its postbiotic can be a potential alternative strategy to oral candidiasis, especially to treat recalcitrant infections. Full article

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, affecting 3–5% of the global population and significantly impacting patients’ quality of life and healthcare resources. Alongside physical symptoms such as abdominal pain and altered bowel habits, many individuals experience psychological comorbidities, including anxiety and depression. Recent research has highlighted the critical role of the gut microbiota in IBS, with dysbiosis, characterized by an imbalance in microbial diversity, frequently observed in patients. The gut–brain axis, a bidirectional communication network between the gut and central nervous system, plays a central role in the development of IBS symptoms. Although interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) have demonstrated potential in modulating the gut microbiota and alleviating symptoms, their efficacy remains an area of ongoing investigation. This review examines the interactions between the gut microbiota, immune system, and brain, emphasizing the need for personalized therapeutic strategies. Future research should aim to identify reliable microbiota-based biomarkers for IBS and refine microbiome-targeted therapies to enhance patient outcomes. Full article

Background: Disorders of glucose and lipid metabolism, such as obesity, diabetes mellitus, or hypercholesterolemia, can cause serious complications, reduce quality of life, and lead to increased premature mortality. Olivetol, a natural compound, could be proposed as a promising therapeutic agent for preventing, treating, or alleviating metabolic complications of such pathological conditions. Methods: In this study, the researchers conducted a broad parallel investigation of olivetol’s effects on metabolic state and gut microbiota functionality in mouse models of alimentary obesity, diabetes mellitus type 1 and 2, and hypercholesterolemia. Results: According to the results of the study, olivetol caused a lowering of body weight in C57Bl6 mice fed a high-fat diet and in ldlr(−/−) mice, decreased serum glucose levels in db/db mice, improved lipid metabolism in ldlr(−/−) mice, and prevented inflammatory infiltration of the pancreas and loss of insulin secretion in NOD mice. In addition, olivetol affected the composition and functional activity of gut microbiota communities, inducing an expansion of probiotic species such as Akkermansia muciniphila and Bacteroides acidifaciens and depleting the representation of pathobionts such as Prevotella, although olivetol supplementation did not influence the diversity or richness of the communities. Conclusions: These results suggest that olivetol is a promising therapeutic agent for preventing, treating, or alleviating the metabolic complications of obesity, diabetes mellitus type 1 and 2, and hypercholesterolemia; however, more investigations are required in order to attain a full understanding of its physiological effects. Full article

Bile salt hydrolase (BSH), a probiotic-related enzyme with cholesterol-assimilating and anti-hypercholesterolemic abilities, has been isolated from intestinal bacteria; however, BSH activity of bacteria in bile-salt-free (non-intestinal) environments is largely unknown. Here, we aimed to identify BSH from non-intestinal Enterococcus faecium and characterize its enzymatic function. We successfully isolated a plasmid-encoded bsh (efpBSH) from E. faecium, and the recombinant EfpBSH showed BSH activity that preferentially hydrolyzed taurine-conjugated bile salts, unlike the activity of known BSHs. EfpBSH functioned optimally at pH 4.0 and 50 °C. EfpBSH exhibited very low amino acid sequence similarity (48.46%) to EfBSH from E. faecalis T2 isolated from human urine, although 241 sequences with 100% identity to EfpBSH were found in both plasmids and chromosomes of E. faecium strains inhabiting intestinal and non-intestinal environments. Phylogenetically, EfpBSH was not affiliated with any known BSH phylogroup and was clearly distinguished from previously identified BSHs from intestinal lactic acid bacteria. Our genome database analysis demonstrated that horizontal gene transfer causes global efpBSH distribution among E. faecium strains in various environments (soil, water, and intestinal samples) and geographical regions (Asia, Africa, Europe, North America, South America, and Australia/Oceania). Overall, our findings are the first to indicate that BSH is not an intestine-specific enzyme and that hitherto-overlooked probiotic candidates with BSH activity can exist in diverse environments. Full article

In the current era, malnutrition is seen as both undernutrition and overweight and obesity; both conditions are caused by nutrient deficiency or excess and improper use or imbalance in the intake of macro and micronutrients. Recent evidence suggests that malnutrition alters the intestinal microbiota, known as dysbiosis. Secretory immunoglobulin A (sIgA) plays an important role in maintaining and increasing beneficial intestinal microbiota populations and protecting against pathogenic species. Depletion of beneficial bacterial populations throughout life is also conditioned by malnutrition. This review aims to synthesize the evidence that establishes an interrelationship between diet, malnutrition, changes in the intestinal flora, and sIgA levels. Targeted nutritional therapies combined with prebiotic, probiotic, and postbiotic administration can restore the immune response in the intestine and the host’s homeostasis. Full article