The oral–gut microbiota axis is a relatively new field of research. Although most studies have focused separately on the oral and gut microbiota, emerging evidence has highlighted that the two microbiota are interconnected and may influence each other through various mechanisms shaping systemic health. The aim of this review is therefore to provide an overview of the interactions between oral and gut microbiota, and the influence of diet and related metabolites on this axis. Pathogenic oral bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, can migrate to the gut through the enteral route, particularly in individuals with weakened gastrointestinal defenses or conditions like gastroesophageal reflux disease, contributing to disorders like inflammatory bowel disease and colorectal cancer. Bile acids, altered by gut microbes, also play a significant role in modulating these microbiota interactions and inflammatory responses. Oral bacteria can also spread via the bloodstream, promoting systemic inflammation and worsening some conditions like cardiovascular disease. Translocation of microorganisms can also take place from the gut to the oral cavity through fecal–oral transmission, especially within poor sanitary conditions. Some metabolites including short-chain fatty acids, trimethylamine N-oxide, indole and its derivatives, bile acids, and lipopolysaccharides produced by both oral and gut microbes seem to play central roles in mediating oral–gut interactions. The complex interplay between oral and gut microbiota underscores their crucial role in maintaining systemic health and highlights the potential consequences of dysbiosis at both the oral and gastrointestinal level. Some dietary patterns and nutritional compounds including probiotics and prebiotics seem to exert beneficial effects both on oral and gut microbiota eubiosis. A better understanding of these microbial interactions could therefore pave the way for the prevention and management of systemic conditions, improving overall health outcomes.

Traditionally studied in isolation, the oral and gut microbiota are now being recognized as interconnected through anatomical and physiological pathways forming a dynamic “oral–gut microbiota axis”. Both oral and gut microbiota undergo changes with aging, characterized by a decline in microbial diversity and a shift toward potentially harmful species. The aim of this review is, therefore, to provide an overview of oral–gut communications in mediating frailty and sarcopenia. PubMed, EMBASE and Scopus databases were searched for relevant articles. We limited our search to manuscripts published in the English language. Interactions between oral and gut microbiota occur mainly through three pathways namely the enteral, the bloodstream and the fecal-oral routes. Alterations in the oral–gut microbiota axis contribute to chronic low-grade inflammation (i.e., “inflamm-ageing”) and mitochondrial dysfunction, key mechanisms underlying frailty and sarcopenia. Microbial metabolites, such as short-chain fatty acids and modified bile acids, appear to play an emerging role in influencing microbial homeostasis and muscle metabolism. Furthermore, poor oral health associated with microbial dysbiosis may contribute to altered eating patterns that negatively impact gut microbiota eubiosis, further exacerbating muscle decline and the degree of frailty. Strategies aimed at modulating the microbiota, such as healthy dietary patterns with reduced consumption of ultra-processed foods, refined carbohydrates and alcohol, ensuring an adequate protein intake combined with physical exercise, as well as supplementation with prebiotics, probiotics, and omega-3 polyunsaturated fatty acids, are increasingly recognized as promising interventions to improve both oral and gut microbiota health, with beneficial effects on frailty and sarcopenia. A better understanding of the oral–gut microbiota axis offers promising insights into nutritional interventions and therapeutic strategies for the age-related muscle decline, frailty and systemic health maintenance.

The introduction of elexacaftor/tezacaftor/ivacaftor (ETI) therapy has further extended life expectancy of adults with cystic fibrosis (awCF), highlighting the need for increased attention to potential long-term health issues. Given the increasing prevalence of cardiovascular diseases in the ageing population and the presence of cardiovascular risk factors associated with CF, understanding the impact of ETI on cardiometabolic risk factors is a crucial clinical concern. The aim of our prospective observational study was to explore early changes in cardiac and metabolic biomarkers after 6 months of ETI therapy. A total of 58 consecutive awCF were enrolled during clinical stability at the Adult CF Center of the Policlinico Hospital in Milan, Italy between January 2021 and June 2022. Blood samples were obtained before ETI initiation and after 6 months, and underwent central processing for an extended panel of cardiometabolic biomarkers. We observed a rise in cholesterol, triglycerides, apolipoprotein-B and adipokine levels, while inflammatory markers decreased. The direct relationship between leptin and adiponectin suggest a disruption in the normal regulatory mechanisms that control these hormones, potentially leading to metabolic imbalances, such as increased risk of obesity and cardiovascular events. The impact of ETI on cardiovascular risk in awCF is heterogeneous and while it improves some risk factors, such as chronic inflammation, it has a worsening effect on lipoproteins. Our findings suggest that the dysregulation of adipokines could be a potential cause of the metabolic disturbances observed in awCF.

Background: During prolonged FDC therapy, the emergence of FDC non-susceptibility in CRAB has been reported. Here, we report a transmission cluster of FDC-non-susceptible CRAB in four patients, all naïve to FDC treatment, characterized by a premature stop codon and amino acid deletion in the PirA protein. Methods: CRAB strains obtained from patients admitted in a single medicine ward of the IRCCS Fondazione Ospedale Maggiore Policlinico between March and July 2024 were analyzed by WGS and antimicrobial susceptibility testing. Phylogenetic analysis was used to assess their genetic relatedness. Results: Between March and July 2024, an outbreak of 33 CRAB was observed among hospitalized patients in a single ward at IRCCS. Genomic analysis, available in 29 cases, revealed that 24 isolates belonged to ST208/1806, 4 to ST369, and one to ST195/1816 (according to the Oxford scheme). FDC susceptibility was affected only in the four ST369 isolates (Kirby-Bauer disk diffusion diameter: 13 mm; UMIC^® method MIC: 4 mg/L), all characterized by a premature stop codon followed by a 52 amino acid deletion located between the amino acids 377 and 428 of the siderophore-drug receptor PirA. No other relevant mutations were detected in the iron-uptake genes. Core-genome ML tree including ST369 reference strains revealed that the four ST369 isolates were highly related and formed a distinct cluster (SNP distance: 3 [IQR: 1–6]). Of note, the four isolates were collected from four FDC-naïve individuals, two experiencing a CRAB-mediated infection. Conclusions: Our findings alert about the circulation of clones carrying modified siderophore-drug receptors without evidence of previous FDC treatment and support the importance of testing FDC susceptibility appropriately before its administration.

Background: Lung transplantation (LUTX) is frequently complicated by Primary Graft Dysfunction (PGD), a heterogeneous form of acute lung injury associated with multi-organ failure and rejection. We hypothesized that early, bedside plasma biomarkers could capture this biological heterogeneity, identifying phenotypes with differential clinical outcomes. Methods: This two-year prospective single-center observational study enrolled 78 bilateral LUTX recipients. With a real-time point-of-care immunoanalyzer we measured IL-1β, IL-2, IL-6, IFN-γ, TNF, CCL-2, IL-15, Ferritin, and D-dimer 36 hours post-reperfusion. Outcome-agnostic Latent Profile Analysis (LPA) was applied to identify bio-signatures. PGD (grade 3) incidence and clinical outcomes were compared across classes. Results: LPA identified three distinct classes, interpreted as biological sub-phenotypes. The Adaptive phenotype (68%) had the lowest inflammatory activation, shortest vasoactive support and Invasive Mechanical Ventilation (IMV) (both 1 day) and ICU stay (3 days), and lowest 72-hours PGD (8%) and Acute Kidney Injury (AKI) (28%) rates. The Hyperinflammatory phenotype (18%) showed the highest IL-6 and Ferritin levels with resolving PGD (69% to 23%, from 6 to 72 hours), but prolonged IMV (6 days), vasoactive support (3 days), ICU stay (7 days), with a high AKI rate (69%). The Coagulopathic phenotype (15%), requiring more intraoperative blood products, exhibited the highest TNF and D-dimer with persistent PGD (36% at 24 and 72 hours), intermediate vasoactive support (2 days), and AKI severity. Six-month rejection-free survival was similar across phenotypes. Conclusions: This preliminary hypothesis-generating study suggests that point-of-care biomarkers after LUTX may identify biological phenotypes with potential clinical relevance. Future studies are needed to confirm such phenotyping.