Nanotechnology is rapidly advancing in biomedical, pharmaceutical, environmental and consumer applications, leading to increasing exposure of humans to engineered nanomaterials (ENMs) with a corresponding growing interest in their interactions with the human microbiome. The microbiome, often referred to as the “hidden organ” and plays a critical role in immune regulation, metabolism, tissue homeostasis, and disease processes. Experimental and preclinical studies suggest that nano-sized particles can directly and indirectly affect microbial ecosystems by mechanisms such as generation of reactive oxygen species, disruption of microbial membranes, quorum sensing disruption, and modulation of microbial signaling pathways. These interactions have therapeutic implications as well as potential toxicological implications. Nanomaterials have shown promise in pre- clinical studies for multiple applications such as antimicrobial therapy, disruption of biofilms, modulation of the microbiome, smart wound healing, and precision medicine, particularly by combining hydrogels, probiotics, and stimuli-responsive systems in microbiome-responsive nanoplatforms. However, emerging evidence indicates that long-term exposure to nanoparticles may contribute to dysbiosis, chronic inflammation, the emergence of antimicrobial resistance, immune system dysfunction and ecosystem disruption, although the clinical significance of these effects in humans remains limited. This review provides a comprehensive overview of nano-microbiome interactions, therapeutic applications, toxicological risks, novel advancements in organoid models, multi-omics technologies, artificial intelligence-based prediction, and personalized nanomedicine based on the microbiome for future clinically relevant therapeutic strategies, while highlighting existing knowledge gaps and future research areas that would be useful for clinical translation.
Multidrug-resistant Candida infections represent a critical therapeutic challenge, particularly among immunocompromised patients and in healthcare-associated settings. In this study, the in vitro antifungal and anti-virulence activities of the ethyl acetate extract of Saussurea costus leaves were systematically investigated against clinical Candida isolates. Among 80 clinical specimens examined, 57 Candida isolates were recovered and identified through conventional phenotypic methods, CHROMagar™, and the VITEK® 2 automated identification system. Candida albicans was the predominant species (50.9%), followed by C. tropicalis and C. krusei (24.6% each). Antifungal susceptibility analysis revealed significant variability among tested agents (p < 0.001), with clotrimazole, nystatin, ketoconazole, and amphotericin B showing the highest inhibitory activity, whereas itraconazole and fluconazole exhibited comparatively lower activity and higher resistance rates. Hemolytic profiling demonstrated that the majority of isolates were non-hemolytic (75.42%), while 24.56% exhibited β-hemolytic activity, with significant differences among isolates (p < 0.05).The ethyl acetate extract of S. costus leaves (extraction yield: 1.4% w/w) demonstrated reproducible antifungal activity against multidrug-resistant Candida isolates, with inhibition zones ranging from 14.0 ± 2.1 to 23.0 ± 2.5 mm. The majority of isolates exhibited MIC values of 31.25 mg/mL, whereas isolate 23 showed reduced susceptibility with a higher MIC of 62.5 mg/mL (p < 0.001). The extract significantly inhibited biofilm formation, with MBIC values ranging from 0.488 to 7.813 mg/mL (p < 0.05). In the hyphae-competent isolate 32, extract treatment markedly suppressed filamentation, reducing hyphal formation from 78 ± 4% in untreated controls to 8 ± 2%, accompanied by significant decreases in hyphal length (31.5 ± 2.1 to 4.7 ± 1.3 μm) and hyphal density (120 ± 10 to 15 ± 3 cells/field) (p < 0.001). Scanning electron microscopy further confirmed pronounced disruption of biofilm architecture, characterized by reduced surface coverage (approximately 85% to 48–50%), increased porosity (approximately 10–12% to 32–35%), and significant reductions in biofilm cluster size and density (p < 0.001). GC–MS profiling revealed a chemically diverse composition, with multiple constituents putatively identified by spectral library matching, including eugenol, caryophyllene oxide, myristicin, fatty acid esters, and a major compound tentatively assigned as dehydrocostus lactone. Collectively, these findings demonstrate that the ethyl acetate extract of S. costus exhibits statistically supported in vitro antifungal and anti-virulence activities against multidrug-resistant Candida isolates. However, these findings remain preliminary and restricted to in vitro evaluation; further studies involving bioassay-guided fractionation, compound-level validation, safety assessment, mechanistic investigations, and in vivo evaluation are required to determine its biological significance and translational potential.
Background Pseudomonas aeruginosa is a significant opportunistic pathogen responsible for a wide range of infections. The growing prevalence of antimicrobial resistance in clinical settings has led to a greater reliance on last-resort agents such as colistin. Notably, such antibiotics have long been used in veterinary practices, possibly playing a role in the emergence of resistance. However, despite the growing concern over colistin resistance, no previous systematic review and meta-analysis has estimated the global prevalence of colistin-resistant P. aeruginosa in non-clinical samples. This study aimed to assess the global prevalence of colistin resistance in P. aeruginosa isolates from non-clinical sources through a systematic review and meta-analysis. Methods A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus for studies published up to January 2025. Eligible studies reporting colistin resistance in P. aeruginosa from environmental, animal, or food-related samples were included. A random-effects meta-analysis was used to estimate the pooled prevalence of resistance. Subgroup analyses were performed based on publication year, continent, country, testing guidelines, antimicrobial susceptibility testing methods, and sample source. Results A total of 70 studies were included. The pooled global prevalence of colistin resistance in non-clinical P. aeruginosa isolates was 5% (95% CI: 1–10%), with substantial heterogeneity (I2 = 97%). Subgroup analyses revealed significant variations: the highest resistance was observed in milk samples (47%, 95% CI: 3–94%), in North America (18%, 95% CI: 0–69%), and in Turkey (30%, 95% CI: 0–100%). Resistance increased over time from 7% in 2013 to 21% in 2024 (a 14% increase). No significant publication bias was detected (Egger's test p = 0.54). Conclusion The rising prevalence of colistin resistance in non-clinical P. aeruginosa isolates underscores the urgent need for enhanced antimicrobial surveillance. Standardizing susceptibility testing methods and restricting colistin use in veterinary settings are essential steps to preserve its efficacy and limit the spread of resistance.
Acinetobacter baumannii is a clinically significant pathogen due to its rapid acquisition of multidrug resistance (MDR) and its robust biofilm-forming ability, which contributes to treatment failure. Hence, the current study was designed to examine the structural, biochemical, and genomic characteristics, as well as the antibiofilm potential, of the phytochemical flavone in mature biofilms. Structural and biochemical analysis revealed that the tested clinical isolate produced a thick extracellular polymeric substance (EPS) matrix enriched in polysaccharides and proteins. Whole-genome sequencing (WGS) identified virulence factors such as AdeFGH efflux pumps, PNAG biosynthesis systems, which are crucial in biofilm formation, and resistance determinants, including β-lactamases (ADC-76, OXA-68), fluoroquinolone resistance mutations in parC that contribute to its antimicrobial resistance. Further, the antimicrobial assays demonstrated that flavone inhibited planktonic growth, and biofilm inhibition studies revealed concentration-dependent disruption of mature biofilms, with bactericidal and antibiofilm effects observed at 2xMIC levels. Drug-likeness and pharmacokinetic evaluation using SwissADME indicated that flavone meets the major criteria for oral drug-likeness. Overall, these findings provide integrated insights into A. baumannii biofilm biology and support flavone as a promising natural candidate for combating biofilm-mediated survival in drug-resistant A. baumannii.
