The gut microbiome has emerged as a critical regulator of human aging and healthspan, with age-related dysbiosis increasingly implicated in a broad spectrum of aging-associated diseases. This review synthesizes evidence linking gut microbial alterations to infectious diseases, antimicrobial resistance, autoimmune, neurodegenerative, psychiatric, cancer, metabolic, kidney, cardiovascular, bone, and muscular diseases, highlighting shared mechanisms such as chronic inflammation, immune dysregulation, and metabolite imbalance. We further explore how enabling technologies, including functional multi-omics, synthetic biology, artificial intelligence-driven analytics, biobanking, and autologous fecal microbiota transplantation, are revolutionizing microbiome research and the design of interventions. Ethical considerations surrounding microbiome-based therapies are also addressed. To translate these scientific insights into clinical innovations, we formulate the PRIME framework: a five-phase roadmap encompassing Profiling, Reviewing, Identifying, Mapping, and Evaluating microbiome-based interventions. By integrating microbiome science, aging biology, and emerging technologies, this review provides a comprehensive blueprint for advancing precision medicine and promoting healthy aging. Furthermore, it emphasizes the importance of building future-ready capabilities to navigate the evolving landscape of age-related diseases and microbiome-driven therapeutic innovations.

Many bacterial immune systems recognize phage structural components to activate antiviral responses, without inhibiting the function of the phage component. These systems can be encoded in specific chromosomal loci, known as defense islands, and in mobile genetic elements such as prophages and phage-inducible chromosomal islands (PICIs). Here, we identify a family of bacterial immune systems, named Tai (for ‘tail assembly inhibition’), that is prevalent in PICIs, prophages and P4-like phage satellites. Tai systems protect their bacterial host population from other phages by blocking the tail assembly step, leading to the release of tailless phages incapable of infecting new hosts. To prevent autoimmunity, some Tai-positive phages have an associated counter-defense mechanism that is expressed during the phage lytic cycle and allows for tail formation. Interestingly, the Tai defense and counter-defense genes are organized in a non-contiguous operon, enabling their coordinated expression.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical global health threat, with ST101 identified as a major circulating clone in Saudi Arabia. We used whole genome sequencing and plasmid reconstruction to investigate the molecular characteristics of CRKP ST101 isolates from Saudi Arabia (2018–2021), analyzing antimicrobial resistance genes (ARGs), virulence factors, and plasmid structure and replicon types. Clinical isolates were obtained from the Ministry of National Guard Health Affairs (MNGHA) hospitals in Saudi Arabia between 2018 and 2021. Whole-genome sequencing was performed using the Illumina MiSeq^® platform, followed by comprehensive bioinformatic analysis of ARGs, virulence factors, and plasmid content. All ten isolates belonged to ST101 and harbored extensive antimicrobial resistance (AMR) and virulence determinants. Nine isolates (90%) carried bla_OXA-48, with three co-harboring bla_NDM-1, representing dual-carbapenemase producers. These carbapenemase genes were located on plasmids with distinct replicon types, including IncL/M, IncHI1B/IncFIB, and IncFIA/IncR. All isolates were multidrug-resistant (MDR), with half classified as extensively drug-resistant (XDR). Four isolates exhibited hypervirulent profiles, harboring aerobactin and yersiniabactin siderophores. This study provides comprehensive genomic characterization of CRKP ST101 in Saudi Arabia, revealing complex resistance mechanisms mediated by diverse plasmid types. The findings highlight the importance of genomic surveillance to track the evolution and dissemination of high-risk MDR and XDR lineages and inform targeted infection control strategies.

Olea europaea subsp. laperrinei, endemic to the central Sahara in Algeria, Niger, and Sudan, is recognized for its therapeutic and nutritional benefits, notably its antioxidant and antibacterial properties. This study investigates the phytochemical composition and biological activities of its leaf extracts obtained via aqueous and ethanolic extraction. Total phenols, flavonoids, and tannins were quantified by UV–visible spectrophotometry, while individual phenolic compounds were identified by HPLC-UV. Antioxidant capacity was measured using DPPH radical scavenging, hydrogen peroxide neutralization, and β-carotene bleaching assays. Antibacterial activity was evaluated against nine bacterial strains. The ethanolic extract exhibited higher total phenol (134.72 ± 9.25 mg GAE/g VP) and flavonoid (26.08 ± 1.57 mg QE/g VP) contents, while tannin levels were similar in both extracts. Twenty-seven phenolic compounds, including oleuropein, hydroxytyrosol, rutin, and quercetin, were identified. The ethanolic extract showed superior antioxidant capacity, with an EC₅₀ of 7.48 ± 0.39 µg/mL (DPPH) and IC₅₀ values of 214.04 ± 2.89 µg/mL (H₂O₂) and 185.63 ± 3.84 µg/mL (β-carotene). Both extracts exhibited antibacterial effects, with inhibition zones up to 23.33 ± 0.76 mm and MIC values as low as 0.78 mg/mL. These findings highlight the potential of Laperrine olive leaves as natural antioxidant and antibacterial agents.

Background: Ventriculoperitoneal shunting (VPS) is the primary treatment for hydrocephalus, significantly improving patients’ outcomes. However, it is marred by high failure rates due to infections, which account for a third of these malfunctions and escalate morbidity, mortality, and healthcare costs. Method: This study focused on evaluating VPS infection rates, pathogens, their resistance patterns, and the impact on clinical outcomes using retrospective data from multiple hospitals in Saudi Arabia. It included data from hydrocephalus patients who underwent VPS and only considered positive cultures that were confirmed from CSF or shunt tip samples. Results: This study excluded patients with prior infections before VPS placement or those treated with alternatives to VPS. Out of 317 patients who met the inclusion criteria, the analysis revealed that 23 patients (7.26%) suffered from VPS infections, mostly within the first two weeks post-surgery (58.06% of cases), with a significant discrepancy in infection rates between hospitals. Infections predominantly involved Gram-positive bacteria (58.08%), especially coagulase-negative staphylococci and Staphylococcus aureus (25.81% and 12.90%, respectively). There was also a substantial presence of Gram-negative bacteria and fungi, accounting for 35.46% and 6.46%, respectively. Despite general antibiotic susceptibility, resistance was significant in certain cases, including multidrug-resistant isolates like Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter ursingii. Importantly, patients with VPS infections had a tenfold increase in the length of hospital stay (70.84 days, SD ± 139.5) compared to non-infected patients (7.69 days, SD ± 20.72), indicating high morbidity and associated treatment costs. Conclusions: Our results emphasize the importance of better VPS infection control and standardized hospital protocols to decrease the incidence of VPS-related infections, both in Saudi Arabia and globally.

Enterobacter cloacae (E. cloacae) is an important healthcare-associated pathogen with increasing antimicrobial resistance. Prophages and phage-inducible chromosomal islands (PICIs) are integral components of the E. cloacae genome, yet their contribution to resistance, virulence, and anti-phage defense remains poorly understood. To address this gap, we analyzed 35 complete E. cloacae genomes, identifying 139 intact prophages (10.8–85.7 kb) with an average GC content (~52%) close to that of the host (54–55%). Most prophages (86.6%) were assigned to the families Peduoviridae and Drexlerviridae within the class Caudoviricetes, and proteome-based clustering showed strong relatedness to phages infecting Enterobacteriaceae. The E. cloacae genomes harbored multiple antimicrobial resistance genes, notably fosA (97%), oqxA/oqxB (89%) and blaCMH-3 (77%). However, on genomic-context verification none were genuinely prophage-encoded; they were instead located on the chromosome or plasmids. Virulence profiling revealed universal presence of ompA and high prevalence of csgG (94%), while the only confirmed prophage-encoded virulence determinants were the Shiga toxin genes stxA and stx1B. Additionally, 16 phage satellites were identified, containing conserved integration, replication, and packaging modules together with diverse accessory and anti-phage defense systems. Overall, prophages and phage satellites drive genome diversification in E. cloacae, with satellites notably serving as reservoirs of anti-phage defense, whereas resistance and virulence genes are located outside prophage and satellite regions.