PubMed

Odontology. 2026 Jun 15. doi: 10.1007/s10266-026-01428-x. Online ahead of print.ABSTRACTBruxism is a heterogeneous jaw-muscle activity with multifactorial neurobiological underpinnings, and adult evidence on molecular and omics-related biomarkers remains fragmented. This systematic review with functional meta-synthesis and exploratory meta-analysis aimed to identify, critically appraise, and synthesize molecular and omics-related biomarkers associated with bruxism in adults. PubMed/MEDLINE, Scopus, and Embase were searched from inception to March 2026, without language restrictions. Eligible studies included adult human participants with bruxism and extractable biomarker comparisons. Data extraction and risk-of-bias assessment were performed independently by two reviewers using design-specific tools and complementary criteria for genetic, omics, and genomic causal-inference studies. Narrative synthesis and functional meta-synthesis were the primary analytic approaches; random-effects meta-analysis was performed for comparable salivary cortisol studies. Ten studies were included. Four biological domains were identified: neuroendocrine stress-related signaling, genetic susceptibility or genomic liability, inflammation and peripheral physiological dysregulation, and multi-omics oral-brain communication. Stress-related biomarkers, particularly salivary cortisol, showed the most recurrent signal, although findings were inconsistent. Genetic and genomic studies suggested possible inherited susceptibility, but the evidence was heterogeneous. Exploratory meta-analysis of three salivary cortisol studies suggested higher cortisol levels in adults with bruxism (standardized mean difference = 0.91; 95% Confidence Interval: 0.21 to 1.60), with substantial heterogeneity (I² = 76.4%). Overall, current evidence suggests possible convergence around stress-related endocrine markers, particularly cortisol, in adults with bruxism; however, the evidence remains heterogeneous, methodologically limited, and insufficient to define a reproducible biomarker signature.PMID:42295535 | DOI:10.1007/s10266-026-01428-x

J Appl Microbiol. 2026 Jun 15:lxag138. doi: 10.1093/jambio/lxag138. Online ahead of print.ABSTRACTInterstitial lung disease (ILD) is a heterogeneous condition that affects the lung parenchyma with varying degrees of inflammation and/or fibrosis. Several studies have suggested a potential link between the gut microbiome and the pathophysiology of lung diseases, including ILD. Accumulating evidence supports bidirectional gut-lung axis interactions potentially mediated by the microbiota. Alterations in the gut microbiome have been associated with the onset and severity of interstitial lung disease. This review aims to summarize findings from in vivo and clinical studies that have investigated the associations between the gut microbiome and ILD. Changes in the gut microbiome have been consistently found in various ILD subtypes, including idiopathic pulmonary fibrosis, radiation pneumonitis, silicosis, coal worker's pneumoconiosis, and connective tissue disease-related ILD. Preclinical studies demonstrate that gut dysbiosis is associated with altered immune responses, increased pro-inflammatory cytokines, and enhanced fibrotic pathways, with mechanistic evidence suggesting the involvement of specific microbial metabolites (short-chain fatty acids, bile acids, and immune mediators. Interventional studies in animal models suggest that fecal microbiota transplantation may attenuate pulmonary inflammation and fibrosis; however, clinical evidence remains limited. This review synthesizes findings across study types, highlights proposed mechanistic pathways, discusses contradictory results, and identifies critical knowledge gaps requiring future investigation to establish causality and inform potential therapeutic development.PMID:42294946 | DOI:10.1093/jambio/lxag138

mSystems. 2026 Jun 15:e0039226. doi: 10.1128/msystems.00392-26. Online ahead of print.ABSTRACTEarly-life microbial colonization is essential for gut and immune development. Human milk oligosaccharides (HMOs) support the growth of Bifidobacterium infantis (BI). Here, we studied the individual and combined effects of BI and HMOs on the immune and colon transcriptomes and on serum and cecal metabolome. Germ-free mice were randomly assigned to four groups (10-14/group: HMO, BI, BI + HMO, and control [no HMO or BI]). HMO and BI + HMO groups received 5 mg/day each of 2'-fucosyllactose, lacto-N-tetraose, and 3'-sialyllactose for 14 days. BI and BI + HMO received BI ATCC 15,697 (1 × 109 CFU/day) on days 1, 4, and 9. Mono-colonization with BI increased monocytes, macrophages, B cells, CD4+ T cells, and Treg cells in mesenteric lymph nodes (MLN) relative to controls. In the spleen, BI alone increased B cells, dendritic cells, Th17 cells, and ILC3 cells, and enriched serum amino acid metabolism pathways. Additionally, BI influenced colonocyte gene expression and modulated serum metabolites that regulate circadian rhythms. BI + HMO increased MLN Th17 cells and spleen monocytes compared with HMO alone. Collectively, the results of this study highlight the complex interplay among host-microbe-diet interactions and emphasize the importance of considering these interactions when designing strategies to modulate infant health during early life.IMPORTANCE: Early life immune and gut microbiome development are shaped by human milk (HM). One of the most important drivers of these processes is the human milk oligosaccharides (HMOs). Bifidobacterium infantis (BI) possesses a unique enzymatic system that enables efficient HMO uptake and intracellular metabolism, providing a competitive advantage over other microbial species in the breastfed infant gut. To date, the potential direct and synergistic effects of BI and HMO have not been fully explored. The knowledge generated herein identified the independent and synergistic effects of HMOs and BI on gut immune response, serum and cecal metabolites, and colonic gene expression.PMID:42294916 | DOI:10.1128/msystems.00392-26

Anal Chem. 2026 Jun 15. doi: 10.1021/acs.analchem.6c01208. Online ahead of print.ABSTRACTA self-driving metabolomics laboratory has long been envisioned but remains largely unrealized due to the complexity of analytical method design. As an initial step toward this goal, we developed BAGO, a self-optimizing framework for automated liquid chromatography (LC) gradient design in mass spectrometry-based untargeted metabolomics. BAGO aims to enhance global metabolite detection by improving the separation of all compounds, regardless of whether their identities are known or unknown. It operates through a data-driven Bayesian optimization process that iteratively learns from acquired MS data to propose improved gradients. To support this, we propose a global separation index that quantifies coelution among both annotated and unannotated features, enabling robust and structure-agnostic optimization across diverse sample types. Benchmarking across four metabolomics assays involving diverse sample matrices, column chemistries, and gradient durations, BAGO achieved substantial improvements within only 10 optimization iterations by balancing exploration and exploitation. The optimized gradients led to increased numbers of Gaussian-shaped peaks, higher MS/MS acquisition rates, and more annotated metabolites using both identity and analog search approaches. We further applied BAGO to a sex-differentiated metabolomics study of Drosophila abdominal carcasses, completing the workflow in parallel under both initial and optimized gradients. The optimized method resulted in a 41.9% increase in Gaussian-shaped peaks, a 36.8% increase in MS/MS-acquired peaks, and the identification of 18 additional biologically significant metabolites, including sex-associated compounds such as octopamine and pyroglutamic acid. BAGO (https://github.com/HuanLab/bago) is freely available as an open-source tool and represents a generalizable step toward fully automated, self-optimizing experimental workflows in untargeted metabolomics.PMID:42294915 | DOI:10.1021/acs.analchem.6c01208

mBio. 2026 Jun 15:e0037426. doi: 10.1128/mbio.00374-26. Online ahead of print.ABSTRACTThe incidence and mortality rates of cervical cancer are high among women. Growing evidence suggests the key roles of the intratumor microbiome in various solid tumors. However, the intratumoral microbiome in patients with cervical cancer has not been well characterized. In this study, 16S rRNA sequencing was performed on 76 tissues to reveal the features of the intratumoral microbiome, and the highly differentially abundant bacteria Lactobacillus iners/Prevotella bivia were selected for functional verification. Flow cytometry, transwell migration, and invasion experiments, among others, were performed in vitro; subcutaneous tumor formation and lung metastasis experiments were performed in vivo. Additionally, macrophages were cocultured with the L. iners/P. bivia supernatant to evaluate how the intratumoral microbiome affects their polarization, and tumor cell and macrophage transcriptome sequencing was subsequently performed to explore the potential molecular mechanisms involved. Metabolomic analysis of tissues and bacterial supernatants was performed to search for potential carcinogens and cancer suppressors. We determined that the abundance of microbes was greater in cervical cancer tissues than in normal cervical and paracancerous tissues. The relative abundance of Prevotella was correlated with deep stromal invasion, tumor size, clinical stage, and poor survival prognosis in cervical cancer patients. L. iners inhibited the proliferation and promoted the apoptosis of tumor cells, whereas P. bivia significantly promoted cervical cancer cell migration and invasion. Mechanistically, the modulation of phosphorylated PI3K/AKT/mTOR signaling may be involved in the observed effects. P. bivia promoted M2 macrophage polarization by activating phosphorylated STAT3 and NF-κB, but the role of L. iners remains unknown. The amino acid metabolism, carbohydrate metabolism, and lipid metabolism pathways were enriched in differentially abundant metabolites such as glycine, which may be a key molecule. This study provides evidence that the intratumoral microbiome, represented by L. iners/P. bivia, affects tumor biology and macrophage polarization in patients with cervical cancer.IMPORTANCEThe microbiome in cervical cancer tissues significantly differed from that in normal cervical tissues and showed significant correlations with clinicopathological features and survival prognosis. The tumor microbiome affects the biological behavior of cervical tumor cells and the polarization of macrophages through metabolite production, thus playing an important role in the occurrence and development of cervical cancer.PMID:42294912 | DOI:10.1128/mbio.00374-26

J Clin Invest. 2026 Jun 15;136(12):e207022. doi: 10.1172/JCI207022. eCollection 2026 Jun 15.ABSTRACTTraumatic brain injury (TBI) disproportionately kills and disables older adults, yet the biology driving this vulnerability remains unresolved. In this issue of the JCI, Lu et al. combined single-cell transcriptomics, metabolomics, and chromatin profiling in mice, validated in human TBI tissue, to define an age-dependent microglial dichotomy. They report that an NLRP3+/IL-1β-linked state dominates the aged brain, while a Lysozyme+/Lyz2+ state predominates in the young. Microglia-targeted perturbation of NLRP3 and ELF1 each shifted the balance and improved survival in mouse models of TBI, and the repurposed drug Imeglimin improved outcomes in these models, confirming that this pathway is druggable. By connecting NLRP3 inflammasome dominance, ELF1-driven transcription, and glycolytic reprogramming to the loss of a protective Lyz2+ response, this work converts age from a clinical risk factor to a set of druggable microglial targets.PMID:42294901 | DOI:10.1172/JCI207022

J Clin Invest. 2026 Jun 15;136(12):e200316. doi: 10.1172/JCI200316. eCollection 2026 Jun 15.ABSTRACTVitiligo is an autoimmune skin disease characterized by depigmentation, mainly due to CD8+ T cell-mediated destruction of melanocytes. Hyperglycemia exacerbates autoimmune responses and is associated with vitiligo; however, the underlying immunometabolic mechanisms are poorly understood. Here, we demonstrated the correlation between hyperglycemia and vitiligo in a case-control study and demonstrated that hyperglycemia aggravated vitiligo based on a mouse model. Targeted metabolomics identified succinate as the potential metabolite mediating hyperglycemia-aggravated vitiligo. Mechanistically, succinate promotes the activation of CD8+ T cells through succinate receptor 1 (SUCNR1) and promotes keratinocytes to secrete CXCL9 and CXCL10 by enhancing the stability and nuclear translocation of hypoxia-inducible factor-1α, facilitating the skin-homing of CD8+ T cells. Thus, hyperglycemia aggravates vitiligo through succinate/SUCNR1 axis-regulated CD8+ T cell hyperactivation. Our study provides insights into the long-observed yet previously unclear mechanism by which hyperglycemia accelerates vitiligo progression and highlights SUCNR1 as a potential therapeutic target.PMID:42294897 | DOI:10.1172/JCI200316

J Clin Invest. 2026 Jun 15;136(12):e202725. doi: 10.1172/JCI202725. eCollection 2026 Jun 15.ABSTRACTAndrogen deprivation therapy (ADT), a cornerstone of advanced prostate cancer treatment, effectively suppresses androgen signaling but frequently induces systemic metabolic dysregulation. Here, we delineate an unrecognized intestinal steroid/bile acid regulatory axis that mechanistically links androgen suppression to extratumoral metabolic aberrations. HSD3B1 is the most common inherited link to prostate cancer mortality and mediates its effects by regulating steroid metabolism. Integrated metabolomic profiling of patients undergoing ADT revealed a rapid genotype-associated reduction in circulating bile acids, most pronounced in carriers of the adrenal-permissive HSD3B1 (1245C) allele. Surprisingly, analyses in human intestinal tissue and mechanistic investigations in in vitro models identified the terminal ileum as a unique site of HSD3B1 and SLC10A2 (ASBT) coexpression, where catalytically active 3βHSD1 is transcriptionally governed by liver receptor homolog-1 (LRH-1). Pharmacologic or genetic LRH-1 inhibition coordinately suppressed HSD3B1 and SLC10A2 expression and function, while inducing adaptive HSD11B2 upregulation and enhanced glucocorticoid inactivation. This LRH-1-dependent regulatory program persisted independently of androgen and glucocorticoid receptor signaling under in vitro conditions modeling androgen deprivation. These findings establish LRH-1 as a central integrator of intestinal steroidogenesis and bile acid transport and implicate the LRH-1/HSD3B1/SLC10A2 network as a mechanistic driver of ADT-associated metabolic disturbances and a potential target for therapeutic intervention.PMID:42294886 | DOI:10.1172/JCI202725

mSystems. 2026 Jun 15:e0171625. doi: 10.1128/msystems.01716-25. Online ahead of print.ABSTRACTSepsis-induced acute kidney injury (SAKI) remains a major contributor to mortality, yet the impact of environmental factors-particularly humidity-on disease progression is poorly understood. Here, we investigated how short-term high-humidity exposure shapes host susceptibility to SAKI and explored the underlying microbiota- and metabolite-mediated mechanisms. Mice pre-exposed to high humidity exhibited markedly attenuated renal injury and improved survival following cecal ligation and puncture (CLP). Notably, this protective effect persisted after bacterial depletion, but was abolished by amphotericin B treatment, indicating a fungus-dependent mechanism. Internal transcribed spacer sequencing and microbiota manipulation experiments identified Meyerozyma caribbica (M. caribbica) as a humidity-enriched commensal fungus essential for renal protection. Metabolomic profiling further revealed syringic acid (SA) as a key M. caribbica-derived metabolite responsible for the observed benefits. SA suppressed MAPK and NF-κB activation, reduced inflammatory cytokine release, and inhibited macrophage pyroptosis in vitro. Together, these findings demonstrate that high humidity confers protection against SAKI through an M. caribbica-SA axis that modulates macrophage inflammation and pyroptosis, highlighting a previously unrecognized environment-microbiota-host interaction in septic immunoregulation.IMPORTANCESepsis outcomes are traditionally attributed to host immunity and microbial infection, whereas environmental influences remain largely overlooked. This study reveals that short-term environmental humidity profoundly shapes septic kidney injury through a commensal fungus-derived metabolite, establishing M. caribbica and its product syringic acid as key mediators of renoprotection. These findings challenge the conventional bacteria-centered view of sepsis-microbiota interactions and uncover humidity-driven mycobiota remodeling as a critical regulator of immune responses. By defining an environment-fungus-host axis that mitigates macrophage inflammation and pyroptosis, this work provides a conceptual framework for leveraging environmental modulation or fungal metabolites as novel therapeutic strategies for sepsis.PMID:42294869 | DOI:10.1128/msystems.01716-25

Adv Sci (Weinh). 2026 Jun 15:e76072. doi: 10.1002/advs.76072. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is incurable and increasingly attributed to gene-environment interactions. Microplastics (MPs) are omnipresent in the human food chain, yet their impact on neurodegeneration is largely unknown. Here we show that chronic oral exposure to 2-µm amine-modified polystyrene microparticles accelerates cognitive decline, amplifies Aβ deposition, gliosis, and synaptic loss, and cripples autophagic flux in 5XFAD mice through the gut-brain axis. MPs accumulate in the gut, breach the epithelial barrier, and selectively expand the taurine-depleting pathobiont Bilophila, while suppressing taurine-synthesizing commensals. Untargeted metabolomics reveal a systemic taurine deficit that precedes and predicts exacerbated Aβ deposition, gliosis, synaptic loss, and autophagic blockade in 5XFAD mice. Antibiotic-mediated microbiota ablation and fecal microbiota transplantation (FMT) demonstrate that the neurotoxic phenotype is fully microbiota-dependent. Restoring taurine level rebalances microglial homeostasis, reinstates autophagic flux, and rescues memory deficits in MPs-treated 5XFAD mice. Translational validation using Alzheimer's Disease Neuroimaging Initiative (ADNI) plasma shows taurine is significantly lower in AD patients versus cognitively normal controls and inversely correlates with cognitive decline. Our findings identify MPs-induced gut-microbiota dysbiosis as a modifiable environmental driver of AD pathogenesis and establish taurine supplementation as a readily translatable intervention that simultaneously fortifies the intestinal barrier and neutralizes microbiota-mediated neurodegeneration.PMID:42294809 | DOI:10.1002/advs.76072

Adv Sci (Weinh). 2026 Jun 15:e76136. doi: 10.1002/advs.76136. Online ahead of print.ABSTRACTZygotic genome activation (ZGA) is a critical developmental milestone whose metabolic regulation remains unclear. This study identifies a pivotal role for Nicotinamide adenine dinucleotide (NAD+) metabolism in regulating ZGA through poly(ADP‑ribose) polymerase 7(PARP7)-mediated ADP-ribosylation. Using ultra-low input embryo metabolomics, we profiled metabolism from zygote to blastocyst, revealing a significant NAD+ decline at the 2-cell stage. This shift coincided with specific upregulation of the mono-ADP-ribosyltransferase PARP7, confirmed by transcriptomics, quantitative RT-PCR, western blot, and immunofluorescence. Genetic knockdown via trim-away technology or pharmacological inhibition with RBN-2397 caused developmental delay/arrest at the 2-cell stage, impaired blastocyst formation, and defective ZGA. Mechanistically, PARP7 deficiency reduced chromatin accessibility (ATAC-seq), diminished H3K4ac and H3K27ac marks, and impaired RNA polymerase II transcription. Integrated proteomics and ADP-ribosylome analysis of late 2-cell embryos identified UHRF1 as a key PARP7 target, mono-ADP-ribosylated at lysines K30 and K31. This modification stabilized UHRF1 protein (cycloheximide chase), and UHRF1 overexpression partially rescued the transcriptional defects associated with ZGA from PARP7 inhibition. Our findings establish a metabolic-epigenetic axis wherein NAD+ metabolism, via PARP7-mediated ADP-ribosylation of UHRF1, regulates chromatin remodeling and transcriptional activation during ZGA, offering fundamental insights into early development.PMID:42294794 | DOI:10.1002/advs.76136

Microbiol Spectr. 2026 Jun 15:e0206325. doi: 10.1128/spectrum.02063-25. Online ahead of print.ABSTRACTFoodborne pathogens exploit acid resistance (AR) mechanisms to survive harsh environments, such as the stomach, increasing contamination risk. While the sigma factor RpoS and cyclic AMP receptor protein (Crp) are known mediators of AR, their systemic regulatory networks remain unclear. Here, we integrated transcriptomics and metabolomics to dissect RpoS- and Crp-dependent responses in E. coli under simulated gastrointestinal neutral (pH 7.5) and acidic (pH 5.5) conditions. We identified 78 coregulated genes, with RpoS dominating energy/amino acid metabolism and Crp primarily modulating amino acid pathways. Both regulators upregulate membrane components (fatty acids, chaperones, transporters) essential for AR, with transporters NarU (RpoS-dependent) and AmtB (Crp-dependent) conferring exceptional survival at pH 2.5. Surprisingly, Crp activates flagellar genes, whereas RpoS suppresses them during acid stress. Our work provides a systems-level understanding of AR adaptation, offering translational potential for antimicrobial development and bioremediation strain engineering.IMPORTANCEEscherichia coli and other gut bacteria colonize or infect the extremely acidic environment of the gastrointestinal tract through the acid resistance mechanism. Therefore, it is necessary to investigate the acid resistance mechanism of intestinal bacteria. Although RpoS and Crp have long been found to regulate the acid resistance of E. coli, there is a lack of systematic research to analyze its regulatory network under the acidic environment. Through an integrated approach combining genomic analysis, we obtained robust research findings. These results establish a novel theoretical framework for understanding microbial adaptation to acidic environments while offering potential applications for developing new antibiotic targets against intestinal pathogens and engineering industrial bacterial strains with enhanced acid tolerance capabilities.PMID:42294698 | DOI:10.1128/spectrum.02063-25

Appl Environ Microbiol. 2026 Jun 15:e0241925. doi: 10.1128/aem.02419-25. Online ahead of print.ABSTRACTPseudomonas aeruginosa (Pa), a ubiquitous opportunistic pathogen, is notorious for causing diverse life-threatening infections, including lethal lung infections in patients suffering from cystic fibrosis (CF). Pa's ability to adapt to various environments is largely attributed to its metabolic flexibility and extensive regulatory networks. Understanding the mechanisms driving Pa adaptation during colonization of the airways of CF patients is of critical clinical importance. Previous studies by our group and others have shown that elevated Ca2+, a characteristic feature of CF airways, positively regulates virulence factor production in Pa and triggers its transition to a biofilm mode of growth. To generate further insights into Ca2+-dependent adaptations in this pathogen, we aimed to elucidate the regulatory impact of Ca2+ on its metabolism. To characterize Ca2+-induced metabolic alterations, a global untargeted gas chromatography-mass spectrometry-based metabolomics study was performed for both intracellular and extracellular fractions of mid-log and stationary-phase Pa cultures. The altered metabolites were mapped to specific pathways, and selected transcriptional changes and phenotypic outcomes were assayed. Our findings showed that Ca2+ regulates pathways involved in central carbon metabolism, nucleotide synthesis, the shikimate pathway, and glycogen metabolism in both mid-log- and stationary-phase cells. Furthermore, pathways involved in sequestering iron were induced by Ca2+ during both growth phases. Overall, these results indicate that exposure to elevated Ca2+, as within the CF airways, leads to metabolic adjustments and supports Pa survival in this environment.IMPORTANCE: Individuals with the genetic disorder, cystic fibrosis (CF), are predisposed to developing chronic, life-threatening Pseudomonas aeruginosa (Pa) infections. Elucidating the mechanisms that mediate the adaptation of Pa to the CF airways is essential for the development of new therapeutics to treat these infections. Previously, we have shown that elevated Ca2+ levels, such as those detected in CF airways, induce the production of multiple virulence factors, contributing to the overall pathogenicity of Pa. Here, we report that Ca2+ regulates Pa metabolism, affecting multiple pathways, including central carbon, nucleotide, and shikimate pathways. These metabolic alterations contribute to significant physiological outcomes, some of which are pertinent to Pa virulence and survival within the host. These findings suggest that Ca2+ can serve as a host factor that plays a significant role in Pa patho-adaptation to CF airways.PMID:42294690 | DOI:10.1128/aem.02419-25

Adv Sci (Weinh). 2026 Jun 15:e76129. doi: 10.1002/advs.76129. Online ahead of print.ABSTRACTLaevichaulis alte is a slug in the order Systellommatophora that evolved from aquatic ancestors and now faces strong challenges from desiccation, respiration on land, and novel pathogens. Its mucus is essential for water retention, locomotion, and defense. To link terrestrial adaptation with mucus biosynthesis, we generated a gap-free genome assembly of L. alte using PacBio HiFi reads, Oxford Nanopore ultra-long reads, and Hi-C data. The genome shows low heterozygosity and holocentromeric chromosomes. Functional metabolomics revealed marked metabolic shifts between L. alte and the closely related aquatic species Peronia verruculata. In L. alte, differential metabolites were enriched in lipid metabolism, immune regulation, and stress response pathways, consistent with life in a dry and microbe-rich terrestrial environment. Comparative genomics and transcriptomics identified candidate genes linked to mucus secretion and physiological adaptation, including VEGF, ASGR2, and COL6A6. Further analyses highlighted the vascular endothelial growth factor (VEGF) gene family as a key regulator connecting angiogenesis, tissue remodeling, and mucus production pathways in L. alte. Together, this gap-free genome and multi-omics dataset establish a molecular framework that links genomic innovation, mucus biology, and terrestrial adaptation in Systellommatophora, and they offer a basis for understanding ecological niche specialization in land molluscs.PMID:42294640 | DOI:10.1002/advs.76129

mSphere. 2026 Jun 15:e0019126. doi: 10.1128/msphere.00191-26. Online ahead of print.ABSTRACTThe plasmid-borne mcr-1 gene poses a significant threat to global health by conferring resistance to colistin, a critical last-resort antibiotic. While its spread is well documented, the adaptations enabling its concurrent antibiotic resistance and clinical pathogenicity remain unknown. The metabolism of bacterial pathogens has evolved to support virulence in nutrient-limiting host environments. Here, we show that sorbose metabolism promotes the fitness and virulence of mcr-1-positive Escherichia coli (MCRPEC), but does not affect its resistance to colistin or polymyxin B. Notably, the virulence contribution is also observed in an mcr-1-negative background. Genetic disruption of sorbose catabolism (ΔsorD) attenuated MCRPEC virulence and fitness both in vitro and in vivo. Integrated transcriptomic and metabolomic analyses suggest that this attenuation is associated with impaired expression of two major virulence determinants. First, defective sorbose metabolism limits the supply of monosaccharide precursors required for LPS biosynthesis, leading to reduced LPS content. Second, metabolic disruption decreases intracellular cAMP levels, which downregulates fimH expression via a cAMP-dependent signaling pathway, thereby compromising bacterial adhesion. Notably, although sorD deletion enhances biofilm formation, this increase is insufficient to rescue the in vivo virulence defect. Restoration of the sorbose metabolic pathway partially rescues MCRPEC pathogenicity. These findings suggest that sorbose metabolism contributes to MCRPEC pathogenicity by supporting LPS synthesis and regulating fimH expression via cAMP signaling. This study indicates a metabolic link between sorbose utilization and MCRPEC pathogenicity, raising the possibility that sorbose, a common food additive, could facilitate MCRPEC pathogenicity.IMPORTANCEThe spread of colistin-resistant Escherichia coli (E. coli) limits treatment options for life-threatening infections. This study shows that sorbose metabolism, which utilizes a common dietary sugar, contributes to the fitness and virulence of such resistant bacteria without affecting their colistin resistance. Using mcr-1-positive E. coli, we find that this metabolic pathway supports lipopolysaccharide synthesis and, via a cAMP-dependent mechanism, promotes bacterial adhesion. Disabling sorbose catabolism attenuates the pathogen in animal models. These findings suggest a previously unrecognized link between a specific carbohydrate metabolism and pathogenesis in drug-resistant E. coli, raising the possibility that dietary components may influence infection outcomes.PMID:42294624 | DOI:10.1128/msphere.00191-26

mSphere. 2026 Jun 15:e0025626. doi: 10.1128/msphere.00256-26. Online ahead of print.ABSTRACTIntracellular bacteria and protists rely on the host cell to supply many metabolites, but the mechanisms through which pathogens manipulate host metabolism to their benefit are not understood. Here, we demonstrate that when the obligate intracellular parasite Toxoplasma gondii secretes its rhoptry organelle contents into the host cytoplasm before invasion-a process called "kiss and spit"-host cell metabolite abundance is altered in nucleotide synthesis, the pentose phosphate pathway, glycolysis, and amino acid synthesis. U-13C6-labeling metabolomics confirmed that kiss and spit increased the flow of carbon through the pentose phosphate pathway and nucleotide synthesis. An increase in 2,3-bisphosphoglycerate abundance led us to investigate the activation of host cytosolic nucleosidase II (cN-II) to provide purines for the parasite. We found that T. gondii manipulates the host cN-II enzyme to dephosphorylate GMP and IMP that it needs for replication. Furthermore, we found that the approved anti-cancer drug fludarabine, which inhibits cN-II, also inhibits Toxoplasma replication. These results reveal Toxoplasma host cell manipulation and highlight potential therapies for toxoplasmosis.IMPORTANCEA fundamental challenge in parasitology is understanding how intracellular parasites rapidly reprogram host metabolism to support replication. This study reveals that Toxoplasma gondii initiates profound metabolic reprogramming through a "kiss-and-spit" mechanism, secreting effector molecules without invasion. We demonstrate that T. gondii specifically hijacks host cytosolic 5'-nucleotidase II (cN-II) by elevating 2,3-bisphosphoglycerate levels, which allosterically activates this enzyme to generate purines essential for parasite survival. Genetic deletion of host cN-II significantly impairs parasite replication, establishing cN-II as a critical host dependency factor. These findings have important implications for antiparasitic drug development while advancing our understanding of purine metabolism in apicomplexan parasites. More broadly, elucidating the molecular mechanism linking parasite effector secretion to specific host enzyme activation provides a framework for understanding metabolic manipulation across other intracellular pathogens.PMID:42294622 | DOI:10.1128/msphere.00256-26

ACS Omega. 2026 May 29;11(22):32363-32379. doi: 10.1021/acsomega.5c13612. eCollection 2026 Jun 9.ABSTRACTBackground: Type-2 diabetes mellitus (T2DM) poses a formidable global health challenge, characterized by persistent hyperglycemia resulting from insulin resistance and progressive β-cell dysfunction. Liraglutide (LIRA), a GLP-1 receptor agonist, and dapagliflozin (DAPA), an SGLT2 inhibitor, are established therapies with complementary mechanisms. However, the potential synergy of their combination, particularly through modulation of the gut microbiota and host metabolism, remains incompletely understood. To elucidate the gut microbiota-metabolite axis underlying the therapeutic effects of combination therapy in T2DM, we explored the interplay between β-cell function, fecal microbiota composition, and microbial metabolites. Methods: A T2DM mouse model was induced by a high-fat diet and streptozotocin. Mice were treated for 4 weeks with LIRA, DAPA, or their combination (COM). We assessed glycemic control, insulin sensitivity, pancreatic islet morphology, serum biochemistry, gut microbiota (shotgun metagenomic sequencing), and plasma metabolome (nontargeted metabolomics). Integrated multiomics analysis was performed to elucidate microbiota-metabolite interactions. Results: Combination treatment demonstrated superior efficacy compared to monotherapies, resulting in significantly greater improvements in body weight, glucose tolerance, insulin sensitivity, lipid profiles, and liver function. Histologically, COM most effectively restored pancreatic islet architecture, increased β-cell mass, and normalized α/β-cell ratio. Metagenomic analysis revealed that COM induced a unique and restorative remodeling of the gut microbiota, distinct from monotherapies. This was characterized by suppression of pathobionts (e.g., Klebsiella and Enterorhabdus) and enrichment of beneficial taxa (e.g., Akkermansia, Lactobacillus, and Faecalibaculum). Metabolomics profiling showed that COM extensively normalized the diabetic plasma metabolome. Key altered pathways included tryptophan metabolism, sphingolipid metabolism, and branched-chain amino acid degradation. Integrated correlation analysis unveiled significant associations between specific microbial genera and host metabolites, suggesting a functional gut microbiota-metabolite axis underpinning the synergistic benefits. Conclusions: The combination of liraglutide and dapagliflozin exerts synergistic antidiabetic effects that extend beyond glycemic control to encompass pancreatic protection and systemic metabolic improvement. This synergy is mechanistically linked to collaborative remodeling of the gut ecosystem and consequent normalization of host metabolic pathways. Our findings provide a novel rationale for this combination therapy and highlight the gut microbiota as a pivotal target for T2DM management.PMID:42294227 | PMC:PMC13261592 | DOI:10.1021/acsomega.5c13612

Food Chem X. 2026 Jun 5;37:104071. doi: 10.1016/j.fochx.2026.104071. eCollection 2026 Jul.ABSTRACTThe application of Rosa roxburghii Tratt. (RRT) is restricted by its astringency despite its rich nutrient content. This study employed mixed fermentation of RRT juice using Lachancea fermentati and Lactobacillus reuteri. The results showed that the total acidity of the mixed fermentation group (RF) peaked at 20.00 g/L within 12 h, significantly exceeding that of the single-strain fermentation groups. RF enhanced antioxidant activity and exhibited potent in vitro xanthine oxidase (XOD) inhibitory activity, achieving an inhibition rate of 81.72%. Furthermore, RF improved the flavor profile by increasing ester diversity to 14 types while reducing isoamyl alcohol-related off-flavors. Metabolomics and electronic tongue analyses confirmed enhanced umami and richness, driven by the upregulation of flavonoids and umami amino acids. Consequently, co-fermentation showed superior overall performance under the tested conditions in improving flavor and functionality, thereby facilitating the development of high-quality functional beverages.PMID:42294145 | PMC:PMC13262171 | DOI:10.1016/j.fochx.2026.104071

Food Chem X. 2026 Jun 3;37:104066. doi: 10.1016/j.fochx.2026.104066. eCollection 2026 Jul.ABSTRACTSweet potato (Ipomoea batatas (L.) Lam.) is an important tuber crop. This study employed LC-MS/MS to investigate metabolic responses in fresh-cut purple sweet potatoes during short-term storage (0-5 d). Fresh cutting and storage jointly reprogrammed metabolic networks, with both basal metabolite levels and their dynamic changes closely linked to browning and quality deterioration. Amino acids, organic acids, and phenolic compounds were the major responsive classes. L-phenylalanine rapidly accumulated after cutting and remained stable, while L-isoleucine increased continuously, showing a positive association with wound response and browning mitigation. In contrast, several antioxidant phenolic acids and flavonoids significantly declined, suggesting that their depletion weakened antioxidant capacity and was negatively correlated with browning. KEGG analysis showed significant enrichment in phenylpropanoid biosynthesis, flavonoid biosynthesis, and phenylalanine metabolism. These metabolites may serve as potential markers for evaluating storage stability and browning sensitivity in fresh-cut purple sweet potatoes.PMID:42294139 | PMC:PMC13264267 | DOI:10.1016/j.fochx.2026.104066

Brain Behav Immun Health. 2026 Jun 3;55:101279. doi: 10.1016/j.bbih.2026.101279. eCollection 2026 Aug.ABSTRACTPrenatal cigarette exposure (PCE) is a major preventable risk factor for neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD), but the underlying mechanisms extending beyond direct developmental neurotoxicity remain poorly defined. This study investigated the long-term integrative effects of PCE on offspring behavior, neuronal activation, and gut metabolome using an established mouse model. Pregnant C57BL/6 mice were randomly assigned to whole-body cigarette smoke or control air exposure from pre-mating until birth. Compared to controls, PCE offspring exhibited a transient reduction in early postnatal weight gain, followed by a robust hyperactive phenotype in adolescence and adulthood, accompanied by increased despair-like behavior without deficits in social interaction. These behavioral alterations were associated with region-specific neuronal hyperactivation, characterized by a significant increase in c-Fos-positive cells in the paraventricular area (PVA) and basal ganglia (BG) - regions implicated in stress integration and motor regulation, respectively, while no significant changes were detected in the medial prefrontal cortex, hippocampus, basolateral amygdala, or nucleus accumbens. Furthermore, PCE induced selective microglial activation in the PVA, accompanied by impaired intestinal barrier integrity as evidenced by reduced colonic Claudin-5 expression. Untargeted fecal metabolomics revealed a persistent reprogramming of gut metabolic pathways, including glycerophospholipid metabolism, phosphatidylinositol signaling, and arachidonic acid metabolism. Together, these findings demonstrate that prenatal cigarette exposure induces enduring behavioral and metabolic abnormalities that correlate with selective neuroimmune and neuronal alterations, highlighting region-specific gut-brain axis correlates of PCE-induced neurobehavioral alterations.PMID:42294082 | PMC:PMC13264108 | DOI:10.1016/j.bbih.2026.101279