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This study identified key intra-tumor microbial signatures distinguishing head and neck cancers from gastrointestinal cancers and explored their diagnostic and prognostic potential. Intra-tumor microbial data of five cancer types were obtained from the Cancer Microbiome Atlas, and corresponding clinical data were retrieved from the Cancer Genome Atlas. The Wilcoxon test was used to analyze differences in microbial populations. Univariate logistic regression, least absolute shrinkage and selection operator, and recursive feature elimination were sequentially applied to screen optimal microbial markers, and a support vector machine classification model was constructed. A nomogram model and Kaplan-Meier curves were used to validate the predictive and prognostic value of the optimal microbes, respectively. Overall, 463 tumor samples and 47 controls were included. Twenty-three microbes showed significant differences in distribution between head and neck and gastrointestinal tumors; among these, eight overlapping microbes were selected as optimal markers. The SVM model based on these eight microbes achieved AUCs of 0.937 and 0.856 in the training and validation datasets, respectively. The nomogram model constructed with these markers showed high predictive accuracy (C-index = 0.8944 in training, 0.8023 in validation). Kaplan-Meier analysis revealed that high abundance of Capnocytophaga, Lachnospiraceae, and Bacteroidales was significantly associated with longer overall survival in both head and neck tumors and gastrointestinal tumors (all P < 0.05). The eight intra-tumor microbial communities serve as a robust signature for distinguishing head and neck tumors from gastrointestinal tumors. Among these, Capnocytophaga, Lachnospiraceae, and Bacteroidales have potential as prognostic biomarkers to improve survival prediction in cancers.

Hysteroscopes and hemorrhoid band ligators represent valuable diagnostic and therapeutic tools in medicine. These reusable devices require reprocessing, but if reprocessing failures occur, patients are at risk for exposure to pathogenic microorganisms. Experiments were conducted in a research microbiology laboratory. To test the effectiveness of a 12-minute or 4-hour immersion in ortho-phthalaldehyde (OPA) with passive filling of the hysteroscopes and hemorrhoid band ligators narrow lumens for killing the intraluminal microbes. Our results demonstrate that narrow lumens limit the full exposure of pathogenic microbes to high-level disinfectants. These experiments demonstrated that OPA disinfection of the hysteroscope would not eliminate contaminating microbes, which represents a reprocessing failure and an infection risk.

Certain microbes inhabiting the gut have been implicated in maintaining gut homeostasis and promoting gut damage repair. Lachnospiraceae members were highly detected in dysbiotic IL-10 KO mice that displayed similar physiological outcomes as control mice. Lachnospiraceae is a highly diverse family of microbes that have been shown to display both commensal and pathogenic characteristics in the colon environment. We investigated the impact of genetic variation in five Lachnospiraceae strains on lowering cellular inflammation and reactive oxygen species (ROS) levels. Cell-free spent media (CFSM) from Eubacterium rectale resulted in lowered ROS, and nitric oxide levels in stressed colon cells and colon organoids. CFSM-treated organoids showed reduced ROS accumulation, improved epithelial integrity, and partial recovery of barrier function compared to oxidatively stressed controls. We demonstrated through shotgun metagenomics, metabolomics, host RNA sequencing, and molecular techniques that glutathione (GSH) biosynthesized by E. rectale alleviated host ROS damage. We showed downregulation of cell stress and immune response genes, indicating recovery from ROS stress. Chemical depletion of GSH in CFSM confirmed the role of microbial derived GSH in alleviation of ROS in colon cells. In this study, we identify E. rectale as a potential probiotic by lowering colon inflammation and ROS damage through production of reduced glutathione. Microbially derived GSH has not been well established in the Lachnospiraceae family which are a large member of the overall gut microbiota. Understanding more about the impacts of microbial functions including GSH on lowering inflammation is needed to develop potential probiotics or therapies for chronic inflammatory conditions. Video Abstract.

Microbes are ubiquitous in the rhizosphere and play crucial roles in plant health; however, the metabolisms and physiologies of individual species in planta remain poorly understood. In this study, we examined microbial gene expression in response to the maize root environment for seven bacterial species originally isolated from maize roots. We grew each species individually, both in vitro in a minimal medium and in planta, and used differential proteomics to identify functions upregulated specifically when bacteria are grown on maize roots. We identified between 1,500 and 2,100 proteins from each species, with 20%-60% of these proteins being differentially abundant between the two conditions. While we found that transporter proteins were upregulated in all species in planta, all other differentially abundant functions varied greatly between species, suggesting niche specialization in root-associated microbes. Indeed, in vitro assays confirmed that Curtobacterium pusillum likely degrades plant hemicellulose, Enterobacter ludwigii may benefit the plant by phosphate solubilization, and Herbaspirillum robiniae colonizes maize roots more effectively when both of its type VI secretion systems are functional. Together, our findings highlight both conserved and species-specific bacterial strategies for growth in the root environment and lay a foundation for future work investigating the mechanisms underlying plant-microbiota interactions.IMPORTANCEBacteria that live on and around plant roots are important for plant growth and health; however, we still know relatively little about how individual bacterial species behave in this environment. In this study, we looked at seven bacterial species originally isolated from maize roots to understand how they change their metabolism and physiology when grown on the plant versus when grown under laboratory conditions. By doing this, we identified key strategies that bacteria use to survive and thrive in the root environment, including changes in nutrient uptake, metabolism, and secretion systems. We also substantiated some of these behaviors using lab experiments and bacterial mutants. Understanding these species-specific functions helps us learn how bacteria establish themselves on roots and interact with the plant. This knowledge is critical for future efforts to design effective microbial communities that improve crop performance and resilience.

Rhizosphere microbes are vital for plant growth. Dark septate endophytes (DSE) can enhance host plant adaptability and regulate microbial communities, showing promise for yam soil remediation. This study examined how single and mixed inoculations of eight DSE strains affect yam rhizosphere carbon metabolism. Results showed that rhizosphere microbes preferred carbohydrate and amino acid carbon sources. Single inoculations exhibited relatively high overall metabolic activity, whereas mixed inoculations demonstrated distinct advantages in the utilization of specific carbon sources, such as carbohydrates. Key discriminators were phenolic acid, carboxylic acid, and carbohydrate utilization. Different strains enhanced specific pathways: Pe and Fu improved amine metabolism; Ac and Zo excelled in carbohydrate use; Pl boosted polymer metabolism. Changes in carbon metabolism correlated with soil properties: polymer and amine use with pH and SOC; carbohydrate use with AP; phenolic and carboxylic acid use with AN. Soil properties were also altered strain-specifically. The Pe strain emerged as the prime candidate for mitigating yam continuous cropping obstacles by synergistically improving both carbon metabolism and soil quality. These findings aid in developing biofertilizers and rhizosphere remediation strategies.

Investigation of endoscopy-associated outbreaks has underscored the importance of ensuring that reusable endoscopes are clean, intact, and dry to prevent pathogen survival and transmission. Researchers compiled evidence from recent peer-reviewed articles, standards, and reports from governmental agencies, including adverse event reports, safety communications, and inspection reports by state health departments. Researchers created narratives, tables, and figures to illustrate issues with endoscope processing effectiveness. These included sterile processing breaches found during outbreak investigations and the proportion of endoscopes with visible defects, residual soil or microbes, or retained fluid. Nonadherence with standards for endoscope processing is widespread, and inadequate quality assurance has been linked to outbreaks of infection and other adverse outcomes. High-level disinfection did not reliably eliminate microbes, and studies found most patient-ready endoscopes in real-world settings were damaged and dirty. To improve processing outcomes and reduce the risk of patient exposures and infections, routine audits and quality assurance steps including cleaning verification tests and visual inspection, are needed. Sterilization may offer a greater margin-of-safety than high-level disinfection because it is capable of a larger reduction in microbial load, utilizes automated systems, has embedded quality indicators, and provides an endoscope that is packaged and protected from contamination.

Organic nitrogen (ON) transformation is critical for nitrogen retention during composting. Here, pilot-scale windrow composting experiments were conducted using food waste digestate composting (FW) and chicken manure composting (CM) to investigate associations between microbial functional potential and ON dynamics through glutamate-centered carbon-nitrogen metabolism. The results supported a potential pathway in which &#x3b1;-ketoglutarate from the tricarboxylic acid cycle (TCA) coupled with ammonium nitrogen (NH4+) through glutamate metabolism and was associated with ON dynamics. Core functional genes (FW: e.g., glnA, GDH2, GLUD1_2; CM: e.g., gltB, glnA, ureC) were identified, and their associated microbes (FW: e.g., Novibacillus, Planifilum; CM: e.g., Dietzia, Brevibacterium) were further determined using gene-taxon association analysis. Different regulatory patterns were observed between the two practical composting systems The CM microbial network was more connected than the FW network, with 10,732 versus 9,089 edges and graph densities of 0.194 versus 0.148. Additionally, In FW, functional genes made the largest independent contribution to ON variation (25.3%), and ON dynamics were more closely associated with the glutamate dehydrogenase (GDH) pathway and carbon-skeleton availability. In CM, gene-associated microbes made the largest independent contribution (14.2%). Although the glutamine synthetase/glutamate synthase (GS/GOGAT) pathway and urease-related processes exhibited efficient metabolic coupling, peptide-like DON molecular signatures remained relatively abundant during most composting stages. These findings provide a mechanistic framework for optimizing nitrogen transformation and retention during composting.

The gut microbiome is linked to body composition, yet most studies involve probiotic or dietary interventions. This study explored relationships between changes in body composition and the fecal microbiota under natural lifestyle conditions. A repeated-measures design involved 15 adults completing four body composition assessments at 3-month intervals. Fecal samples from each time point underwent 16S rRNA gene sequencing. Participants were stratified by body composition parameters, and microbial profiles from initial and final measurements were compared to assess longitudinal patterns. Overweight participants showed lower alpha diversity. Linear mixed models revealed fecal microbiota remained stable across all four time points, with no statistically significant continuous trends observed longitudinally. Exploratory baseline-to-endpoint comparisons across stratified groups and Spearman correlation analyses suggested potential microbiota shifts, though these associations remained statistically non-significant. Preliminary observations exhibited that the OTU identified as Parasutterella excrementihominis tended to associate with higher body fat, whereas the putative species Akkermansia muciniphila showed a potential inverse association. Representative taxa, such as Dialister invisus, appeared enriched in individuals with higher skeletal muscle percentages, whereas the OTU assigned to Bifidobacterium pseudocatenulatum showed the opposite trend. Several associations differed by sex, suggesting modulation by host factors. These preliminary findings suggest possible fecal microbiota patterns associated with body composition, even without targeted interventions. While lacking robust linear associations in this small pilot cohort, the observed directional consistency across statistical approaches highlights the potential of fecal microbes as candidate indicators of metabolic health. These exploratory results require further validation in larger, longitudinal studies with sufficient statistical power.

The liver receives microbe and host signals from the intestine via the portal vein, thereby connecting the gut to systemic physiology. Homeostatic control of the timing of systemic responses is critical to prevent the expansion and dissemination of gut microbes and to mitigate untoward effects from prolonged systemic inflammation, however these mechanisms remain enigmatic. Here, to determine the role of the liver in coordinating systemic immune responses to enteric infection, matched measurements of global gene expression profiles were collected from the murine liver and intestinal epithelium throughout the course of enteric infection and clearance of Citrobacter rodentium, a mouse model of infectious colitis. These data revealed metabolic suppression in the liver during the peak of infection and a long-lived immune signaling pattern in the colon associated with CD4 and CD8 T cell infiltration that persisted beyond the clearance of infection. Furthermore, an early inflammatory signal was detected in the liver that resolved before the peak of disease and pathogen colonization. This self-limited, early signal depended on the pathogen's virulence program and correlated with the timing of a corresponding systemic response, including circulating TNF-&#x3b1; and IL-6, key mediators of acute-phase proteins. These results uncover the temporal pattern of hepatic changes in response to the course of intestinal infection and provide correlative evidence that an early pulse of gene expression in the liver coordinates and limits the duration of the systemic acute-phase protein response.

Rapid population growth has intensified pressure on freshwater (FW) resources, significantly impacting agricultural practices and worsening food scarcity in many regions. The reuse of treated wastewater (TWW) for irrigation addresses water scarcity but carries the risk of spreading pathogenic microbes and antibiotic-resistant bacteria (ARB). Free-living amoebae (FLA) in soil prey on bacteria and have been proposed as biocontrol agents. Here, we suggest an eco-biological approach, investigating how key ions in TWW (phosphate, ammonium, and sulphate) affect predation by three FLA species (Vermamoeba vermiformis, Acanthamoeba castellanii and Heterolobosea sp.) on model bacterial prey GFP-tagged Escherichia coli and GFP-tagged Enterococcus mundtii. This approach aims to enhance soil microbial safety and reduce pathogen persistence in irrigation systems. We also develop a YOLOv5 deep-learning model to quantitatively track FLA behaviour in microscopy videos. Our results show that PO43- or NH&#x2084;&#x207a; (100&#x2005;mg/L) enrichment greatly enhances Vermamoeba's grazing on E. coli (7 log10 reductions in 72&#x2005;h) compared to controls or SO&#x2084;&#xb2;- addition. Fluorescence microscopy images confirm extensive bacterial interaction and killing by Vermamoeba in PO43- and NH&#x2084;&#x207a; enrichment. In contrast, Acanthamoeba and Heterolobosea had weaker effects. A mixed FLA consortium, however, eliminated E. mundtii faster than any single FLA species. The YOLOv5 model trained on an annotated dataset and validated against manual viable-cell counts reliably tracked FLA movement. These findings suggest that tailoring nutrient levels in TWW can enhance the biocontrol function of FLAs. Our interdisciplinary approach lays groundwork for ecological and AI-informed strategies to make TWW reuse safer.

Background: The oral microbiome comprises the microbial communities inhabiting the oral cavity, whereas the oral metabolome reflects the small molecules generated by host and microbial metabolic activity. These systems may provide insight into substance-related physiological disruption, including altered inflammation, immune signaling, and host - microbial interactions. Although the individual effects of methamphetamine, alcohol, and smoking have been explored, their combined impact on these systems remains largely unexplored.Objectives: To investigate the metabolic and microbiome alterations associated with chronic methamphetamine use in individuals with alcohol and tobacco use.Methods: High-throughput metabolomic and microbiome datasets from methamphetamine users (Males:168, Females: 50), stratified by self-reported tobacco smoking and alcohol use, were analyzed using integrative bioinformatics approaches, including multivariate and pathway enrichment analyses, to identify dysregulated metabolic pathways and microbial alterations across defined subgroups.Results: The study revealed significant upregulation in metabolites like prostaglandin E2 (log-2-fold-change: 2.63, Cohen's D: |~0.881|, p-val: 7.1&#x2009;&#xd7;&#x2009;10-10) and glutamylisoleucine (log-2-fold-change: 1.42, Cohen's D: |~0.88|, p-val: 2.5&#x2009;&#xd7;&#x2009;10-2). Microbes such as Bacteroides (log-2-fold-change: -4.91, Cohen's D: |~1.95|, p-val: 1.3&#x2009;&#xd7;&#x2009;10-4) and Brachymonas (log-2-fold-change: -2.47, Cohen's D: |~1.09|, p-val: 5.8&#x2009;&#xd7;&#x2009;10-3) were significantly downregulated. This suggests that long-term concurrent methamphetamine use, alcohol consumption, and smoking are associated with alterations in microbial and metabolic pathways related to oxidative stress, glutathione metabolism, and neuroactive signaling.Conclusions: The oral microbiome and metabolomic profiles may serve as accessible indicators of substance-related biological disruption. They may also help identify clinically relevant targets for monitoring risk, guiding personalized interventions, and developing informed strategies to support recovery.

Organ-specific immune responses are shaped by tissue microenvironments, which instruct and regulate the behaviour of tissue-resident macrophages and lymphocytes. During infection, microbes are also influenced by tissue-specific environmental signals, which may influence host-microbe interactions and infection outcome. The pathogenic fungus Candida albicans undergoes significant adaptation within the host, associated with major genetic and phenotypic changes as a result of stress responses. These underlie the ability of this yeast to evade host immune responses and establish infection. Recent evidence has pointed to C. albicans phenotypic diversity directly influencing the host microenvironment and therefore localised immune responses. In this review, we discuss organ-specific mechanisms of antifungal defence and fungal tissue-specific phenotypes and stress responses during invasive infection. We focus on C. albicans, the best studied fungal infection in multiple organs, while highlighting lessons learned from other fungal pathogens to signal important future directions for the field.

Melanin is a natural pigment found in plants, animals, insects and microbes. The melanin can be extracted from the natural resources using various methods such as solvent extraction, ultrasonication, enzyme assisted extraction, etc. The functional properties of melanin are useful for developing active packaging film and coatings. Melanin shows several important biological properties such as antioxidant, antimicrobial, UV-light barrier properties which are suitable for food packaging application. Moreover, the reinforcement of packaging polymers with melanin improves its physical properties such as mechanical, thermal and barrier properties. Furthermore, the presence of melanin as a bioactive ingredient in packaging polymers has been extensively reported to enhance the shelf life of perishable foods such as fruits, vegetables, dairy and meat. This chapter discusses the natural melanin incorporated packaging for developing smart food packaging.

Most soil prokaryotic species remain uncultivated, limiting our understanding of the terrestrial microbiome. Metagenomic sequencing, and particularly the study of metagenome-assembled genomes (MAGs), represents an unprecedented opportunity to characterize the genomic features and biogeography of uncultivated prokaryotic taxa at the large scale. Here, we analyze 40,039 genomic bins from cultivated and uncultivated soil taxa within the SMAG catalog, and examine the occurrence of uncultivated prokaryotes in 9,012 metagenomic samples from the Sandpiper resource. Compared to genera with cultivated representatives, uncultivated soil prokaryotes show smaller genomes, lower G&#x2009;+&#x2009;C content, tendency to acidophilic, non-alkaline, thermophilic and host-associated lifestyles, and slower growth rates, with the latter having the highest predictive power for cultivation status. Uncultivated soil microbes also show unique gene repertoires, characterized by a depletion of biosynthetic and motility genes. We also show that completely uncultivated genera are more abundant in tropical and arctic soils, indicating substantial hidden diversity in these regions. Our work emphasizes that current cultivation efforts systematically fail to capture a particular fraction of soil prokaryotic diversity, and provides guidelines for future cultivation strategies.

Airborne microbes significantly influence environmental processes and human exposure, yet they remain poorly characterized in Africa. This study presents a regional survey of airborne bacterial and fungal communities across 10 sites in five East African countries: Burundi, the Democratic Republic of the Congo, Kenya, Rwanda, and Tanzania. Polyurethane foam passive air samplers (PUF-PASs) were deployed concurrently, and airborne bacterial and fungal communities were characterized using 16S rRNA gene and ITS amplicon sequencing. Genus-level analyses identified both bacterial taxa (Massilia, Sphingomonas, Pseudomonas, Bacillus, and Kocuria) and fungal genera (Cladosporium, Alternaria, Aspergillus, Curvularia, and Penicillium) that are commonly detected in outdoor air and urban atmospheric environments. Beta-diversity analysis revealed no significant country-level differences in bacterial communities (ANOSIM (R&#x2009;=&#x2009;-0.045, p&#x2009;=&#x2009;0.597)), while fungal communities exhibited significant differences among countries (ANOSIM (R&#x2009;=&#x2009;0.652, p&#x2009;=&#x2009;0.002)). Cross-border comparisons showed that nearby sites within 10&#x2009;km did not consistently share similar microbial profiles. These findings indicate a broadly shared regional bacterial aerobiome, with more pronounced spatial structuring among fungal communities. This study serves as a proof-of-concept demonstration that PUF-PASs can be used to characterize airborne microbial communities in East Africa, while highlighting the need for future bioaerosol research with enhanced temporal replication and broader spatial coverage to support long-term public health surveillance in the African region.

The intestinal flora forms a complex ecosystem that interacts with the host, influencing health and fitness through mechanisms that connect with distant organs like the brain, liver, muscles, and testes. The gut microbiota plays a vital role in regulating androgen production and metabolism, and can cross the blood-testis barrier to influence spermatogenesis. This review highlights the significance of the gut-testis axis in male reproductive and sexual health, based on extensive studies exploring how gut microbes impact testicular function. Gaining this understanding deepens our knowledge of the gut-testis axis and its role in male reproductive health.

Soil-transmitted helminth infections are widespread and can impair children's nutrition and development. Anthelmintics may interact with the intestinal microbiota; however, they should not disrupt microbes, and microbial metabolism should not reduce drug efficacy. Using Caenorhabditis elegans and representative Gram-positive and Gram-negative gut bacterial lineages, Escherichia coli and Lactobacillus reuteri , respectively, we tested interactions with fluopyram, ivermectin, and levamisole. None of the drugs affected either bacterial growth, and neither bacterial lineage altered nematocidal efficacy. These results help elucidate bacteria-anthelmintic-nematode interactions using tractable experimental models; their direct relevance to in vivo intestinal infections remains to be confirmed.

Diarrhea-predominant irritable bowel syndrome (IBS-D) is characterized by diarrhea and is often accompanied by depression, abdominal symptoms, and emotional comorbidities. Preclinical and clinical studies have shown that dysfunction of the brain-gut axis is a key pathogenic factor in IBS-D, yet the specific mechanisms remain unclear. Saikosaponin D (SSD), a major bioactive component of Bupleurum chinense DC., exhibits anti-inflammatory, antidepressant, and antitumor activities, with multi-target and multi-pathway interactions. Acetic acid and restraint stress induced an IBS-D mouse model. SSD (purity&#x2009;&#x2265;&#x2009;98%, Macklin Inc.) was administered orally at low, medium, and high doses (5, 10, 20&#xa0;mg/kg). Visceral sensitivity, inflammatory status, intestinal barrier function, HPA axis activity, and gut microbiota composition were systematically evaluated using behavioral tests, Western blot, qRT-PCR, and 16S rRNA sequencing. SSD significantly alleviated visceral hypersensitivity and depression-like behavior, inhibited the peripheral HMGB1-TLR4/NF-&#x3ba;B inflammatory pathway, and restored intestinal barrier integrity. SSD also downregulated hypothalamic Nesfatin-1/CRH/p-CREB expression, suppressed hyperactivation of the stress-related HPA neuroendocrine axis, and reshaped the gut microbial community structure (&#x3b2;-diversity). Network pharmacology analysis suggested that SSD targets were significantly enriched in brain-gut axis-related pathways. The present results indicate that SSD could ameliorate IBS-D by synergistically regulating peripheral inflammation, central stress, and intestinal microbes via the brain-gut-microbiota axis, providing experimental evidence for its potential application in TCM-based treatment.

Prior studies have linked the microbiota to brain diseases, whereas the longitudinal effects of the oral microbiota on cortical thinning and cognitive impairments in cerebral small vessel disease (CSVD) remain unexplored. We recruited 120 CSVD patients and 40 healthy controls (HCs). The subgingival plaque microbiota was sequenced by a metagenomic approach. Cortical thickness was assessed using GM-centile, an age- and sex-normalized MRI metric. Differential microbial taxa and KEGG orthologs (KOs) between groups were identified using MaAsLin2. Associations between key differential taxa with CSVD-specific cortical thinning were examined using the Spearman test, and those with MoCA score and plasma inflammatory markers (CRP and lymphocyte counts) were examined by linear regression models. Mediation models evaluated the indirect role of cortical thinning in the relationship between microbial abundance and cognitive function. Generalized estimation equations validated the longitudinal effects of the microbiota on cortical thinning progression. We identified distinct oral microbiota dysbiosis in CSVD, including depletion of g_Selenomonas and g_Leptotrichia and enrichment of g_Treponema. The abundance of these microbes was correlated with longitudinal cortical thinning in the frontal gyrus, insular lobes, and inferotemporal gyrus. Enrichment analysis revealed that CSVD-enriched KOs were linked to the upregulation of LPS-mediated pro-inflammatory pathways, while those depleted were associated with the reduced biosynthesis of neuroprotective short-chain fatty acids (SCFAs). g_Leptotrichia abundance showed negatively correlation with CRP (p&#x2009;=&#x2009;0.045). Mediation analyses indicated that the association between g_Leptotrichia depletion and baseline cognitive impairment was mediated by bilateral insular cortical thinning (both p&#x2009;<&#x2009;0.05). Additionally, the association between g_Leptotrichia depletion and one-year cognitive decline was mediated by superior frontal cortical thinning (p&#x2009;=&#x2009;0.033). Oral microbiota dysbiosis in CSVD patients reflects a pro-inflammatory state, characterized by enhanced LPS synthesis and reduced SCFAs production. This dysbiosis is associated with CSVD-specific cortical thinning in regions vulnerable to neuroinflammation, which in turn mediates cognitive impairment. A major strength of this study is the use of population-based, age-, and sex-normalized cortical thickness measurements to quantify cortical thinning, combined with MaAsLin2 modeling to identify CSVD-associated oral microbiota features. This integrated approach minimizes confounding and enhances the reliability of associations between the oral microbiota and cortical thinning.CSVD patients exhibited distinct oral microbiota dysbiosis characterized by depletion of Selenomonas and Leptotrichia and enrichment of Treponema. KEGG enrichment analysis and plasma inflammatory markers further revealed that this dysbiosis reflects a functional shift toward a pro-inflammatory state, driven by enhanced lipopolysaccharide (LPS) synthesis and dysregulated short-chain fatty acid (SCFA) metabolism.Oral microbiota dysbiosis may accelerate cortical thinning in brain regions vulnerable to CSVD pathology through inflammatory mechanisms, thereby mediating the link between microbial alterations and cognitive outcomes. Specifically, Leptotrichia depletion is associated with baseline cognitive impairment via bilateral insular thinning and with one-year cognitive decline via superior frontal thinning.