npj Biofilms and Microbiomes最新文献

The interplay between nutrient availability and arbuscular mycorrhizal fungi (AMF) symbiosis during plant growth exhibits intricate complexity. In this study, we employ integrated physiological, transcriptomic, proteomic, and metabolomic analyses to investigate how sugarcane differentially adapts to nitrogen (N) fertilization and AMF colonization. Under nitrogen stress conditions, AMF colonization significantly enhances sugarcane growth, increasing plant height, stem diameter, and biomass while stimulating root exudation and rhizospheric nutrient mobilization-particularly available N, phosphorus (P), and potassium (K). Multi-omics analyses reveal that AMF induces nitrogen-dependent metabolic reprogramming in sugarcane roots, activating pathways such as carbohydrate and lipid metabolic pathways while suppressing butanoate and ascorbate metabolism. Weighted gene co-expression network analysis (WGCNA) identifies key root modules strongly correlated with soil N, P, and K availability, indicating AMF-mediated coordination of nutrient acquisition strategies. Field trials demonstrate that AMF boost sugarcane yield under nitrogen stress by enhancing root elongation and carbon partitioning for sucrose accumulation. Temporal integration of transcriptomic and metabolomic data highlights flavonoid biosynthesis as a persistently activated pathway across growth stages, potentially facilitating AMF symbiosis and stress resilience. Our findings elucidate how sugarcane optimizes AMF-mediated nutrient acquisition under nitrogen stress through root transcriptional and metabolic adjustments, providing insights for sustainable crop nutrient management.

Alveolar echinococcosis (AE), a chronic parasitic disease caused by Echinococcus multilocularis (E. multilocularis), remains poorly characterized with respect to central nervous system (CNS) involvement, and its long-term effects on mental health have not been systematically investigated. In this study, we established a BALB/c mouse model of chronic E. multilocularis infection and applied an integrative framework combining behavioral assessments, histomorphological analyses (hematoxylin-eosin staining, Nissl staining, and transmission electron microscopy), cytometric bead array (CBA), and multi-omics approaches (16S rRNA sequencing, metagenomics, and untargeted metabolomics) to investigate infection-induced neuroimmune-gut microbiota interactions. Chronically infected mice exhibited pronounced depression-like behavioral phenotypes, accompanied by hippocampal neuronal nuclear membrane atrophy and disrupted microglial homeostasis. Both peripheral and central inflammatory profiling revealed elevated levels of pro-inflammatory mediators, particularly IL-6 and MCP-1, suggesting coordinated systemic immune activation and neuroimmune alterations. Notably, fecal microbiota transplantation (FMT) from infected donors was sufficient to induce depression-like behaviors in recipient mice, supporting a contributory role of infection-associated gut microbiota alterations in behavioral abnormalities. Integrated multi-omics analyses further revealed a marked reduction in Lactobacillus abundance in infected mice, which was positively correlated with decreased levels of key metabolites within the tryptophan/5-hydroxytryptamine (5-HT) metabolic pathway. Collectively, these findings suggest that chronic E. multilocularis infection may be associated with depression-like behaviors through gut microbiota dysbiosis and related metabolic perturbations. This study provides initial insights into the potential mechanisms underlying neuropsychiatric complications in AE and proposes a conceptual framework for future investigations into early intervention and microbiota-targeted therapeutic strategies.

The coexistence and horizontal transfer of antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) carried by urban wildlife represent an emerging form of biological pollution, constituting a significant threat to public health. We employed meta-omic approaches to evaluate the effects of host traits (sex, age, etc.), environmental factors (including geographical location and time), and diet (including food composition and antibiotic residues) on the bacterial, ARG, and VFG profiles of Vespertilio sinensis, an urban-dwelling bat. Our results demonstrate that the feces of V. sinensis harbor diverse ARGs and VFGs, but their genomic evidence for horizontal mobility in bacterial communities is limited. Notably, environmental changes over time and across geographical locations are associated with the ARG and VFG profiles, potentially due to the influence of pollutants in specific habitats. Dietary factors are associated with their dynamics through the microbiome, with antibiotic residues exerting selective pressure on ARG profiles. No significant impacts of sex, age, body size, and reproductive status on the gut microbiota, resistome, or virulome were observed. This study provides valuable insights into the ecological drivers of the gut microbiome, resistome, and virulome in bats, thereby contributing to our understanding of the public health risks associated with urban wildlife.

Major Depressive Disorder (MDD) affects around 20% of people globally and is often comorbid with anxiety. This study investigates prucalopride, a serotonin type 4 receptor (5-HT₄R) agonist approved for constipation, as a fast-acting anxiolytic/antidepressant using a mouse model of stress, based on corticosterone (CORT) administration. Behavioral effects of prucalopride (0.5 and 1.5 mg/kg/day) were compared to fluoxetine, a common SSRI, over 7 (subchronic) and 28 (chronic) days. Prucalopride showed faster and more significant improvements in emotionality scores than fluoxetine, reversing CORT-induced behavioral changes within 7 days. Gut microbiota analysis revealed CORT-induced changes at the subchronic timepoint. While chronic prucalopride did not alter microbial alpha diversity, it significantly shifted microbial composition (beta-diversity). Notably, prucalopride restored levels of the genus Ruminococcus, which were depleted by CORT. Our findings highlight prucalopride's rapid anxiolytic and antidepressant-like effects and its impact on gut microbiota, supporting the potential of 5-HT₄R-targeting molecules as therapeutic options for psychiatric disorders.

Exopolysaccharides (EPS) are critical components of the biofilm matrix, and ppGpp has been demonstrated to positively influence biofilm formation. Here, we elucidate the underlying mechanism by which ppGpp regulates EPS production by facilitating HpaR1 to modulate the expression of the gum cluster in the phytopathogen Xanthomonas campestris pv. campestris (Xcc). ppGpp affected the yield of EPS without influencing its primary or advanced structure, as confirmed by Fourier transform infrared spectroscopy and scanning electron microscopy. Expression of the gum cluster, which governs EPS biosynthesis in Xcc, was down-regulated in the ppGpp-deficient mutant (ΔrelAΔspoT) compared to the wild type (WT). Comparison of EPS production between knock-out mutants of the gum cluster and ppGpp-deficient mutant revealed that the gum cluster was a key determinant of EPS production, with ppGpp acting upstream of the gum cluster. Transcriptomic and qPCR analyses indicated that ppGpp modulated global transcription in Xcc, positively regulating expression of hpaR1, which encodes the transcription factor for the gum cluster. This regulatory role was further substantiated by electrophoretic mobility shift assays, which showed that ppGpp enhanced the DNA-binding activity of HpaR1. Furthermore, genetic complementation with hpaR1 restored EPS production, confirming its functional role in this regulatory pathway. In summary, these findings provide novel insights into the molecular mechanisms linking ppGpp signaling to EPS production in X. campestris pv. campestris.

Quorum sensing (QS) orchestrates collective microbial behaviors and functional acclimatization through chemical communication. However, QS in natural waters is challenged by dilution, alkaline hydrolysis, and enzymatic degradation of freely dissolved autoinducers. Here, we demonstrate that extracellular vesicles (EVs) act as selective, durable, and protective vectors for QS signal molecules under environmental stresses. Specifically, EVs preferentially package hydrophobic acyl‑homoserine lactones, concentrate them locally, and shield them from alkaline hydrolysis, and exhibiting long-distance transport. In addition, EVs possess specific affinity to recipients, thus influencing microbial community. Field investigation via multi-omics showed that EV abundance covaried with salinity, nutrients, chlorophyll a, and biomass, which were validated by culture experiments. Our statistical framework demonstrated that organisms producing moderate EV levels contributed significantly to maintaining community stability and ecosystem functions. Distinctively within this group, QS-active species (including Burkholderiaceae, Pseudomonadaceae, Rhodobacteraceae, Roseobacteraceae, Flavobacteriaceae etc.) emerge as key drivers facilitating these crucial ecological roles. Furthermore, metaproteomics of field EVs reveal QS receptor and synthesis proteins, suggesting coordinated transport of signals and proteins, which indicate new routes for QS crosstalk, particularly for taxa bearing luxR/I solos. Our results show that moderately generated EVs are the potentially important QS signal carriers and ecological regulation hubs in natural waters.

Renal injury is a common complication of hyperuricemia (HUA), which has been recognized as an independent risk factor for chronic kidney disease (CKD). The gut-kidney axis theory suggests that targeting the gut microbiota may be a potential treatment option for kidney disease. In this study, we utilized a spontaneous HUA rat model to demonstrate that Simiao decoction (SMD), a traditional Chinese medicine formula, can effectively alleviate HUA-induced renal injury by modulating gut microbiota and bacterial metabolism of tryptophan and tyrosine, thereby reducing gut-derived uremic toxins such as indoxyl sulfate (IS) and p-Cresol (PC). Fecal microbiota transplantation (FMT) further confirmed that the therapeutic effect of SMD was mediated by gut microbiota. Finally, in vitro studies revealed that IS promotes epithelial-mesenchymal transition (EMT) while PC induces cellular senescence in tubular cells. Collectively, our findings suggest that SMD can effectively alleviate HUA-induced renal injury through regulating gut dysbiosis and decreasing gut-derived uremic toxins. This study sheds light on a novel mechanism by which SMD exerts its effects on HUA-induced renal injury.

Cognitive impairment (CI) following mild traumatic brain injury (mTBI) poses a clinical challenge, with emerging evidence implicating gut microbiota. This study found that mTBI patients who developed CI exhibited decreased Hungatella hathewayi, while those without CI showed an increase. Microbiota transplantation in mTBI rats revealed that higher Hungatella hathewayi levels enriched beneficial, short-chain fatty acid (SCFA) -producing bacteria and reduced harmful ones. Elevated Hungatella hathewayi improved performance in the Morris water maze and novel object recognition tests, indicating enhanced spatial learning and memory. It also reduced gut and brain inflammation, shown by lower TNF-α and IL-6 mRNA expression, and promoted M2 microglia polarization in the peri-lesional cortex. Metabolomics identified increased fecal and serum butyrate, a SCFA with anti-neuroinflammatory properties. Thus, Hungatella hathewayi may mitigate Post-mTBI CI by boosting butyrate production, which alleviates intestinal inflammation, shifts microglia toward the protective M2 phenotype, reduces neuroinflammation, and supports neuroprotection, ultimately lowering CI risk after mTBI. This study was registered with the Chinese Clinical Trial Registry (ChiCTR) on May 31, 2023 (Registration number: ChiCTR2300072000, URL: https://www.chictr.org.cn/showproj.html?proj=197867).

Inflammatory bowel disease (IBD) involves chronic gastrointestinal inflammation with complex etiologies, where gut microbiota and metabolites have emerged as key pathogenic factors. While earlier studies predominantly focused on fecal bacteria, recent research has shifted to mucosa-associated bacteria, which reside in the intestinal mucus layer and directly interact with the epithelium-critical for IBD pathogenesis. This review synthesizes evidence showing that IBD patients exhibit mucosa-associated bacteria dysbiosis, characterized by increased facultative anaerobes and reduced beneficial taxa, alongside altered mucosal metabolites such as short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO). Notably, mucosa-associated bacteria-driven metabolic changes show promise as early diagnostic markers for IBD. Mechanistically, mucosa-associated bacteria directly modulate intestinal barrier integrity and immune responses via pathways like TLR4-mediated inflammation and mucin degradation, distinct from luminal microbiota studied in fecal samples. This review highlights novel therapeutic strategies targeting mucosa-associated bacteria and mucosal metabolites, including probiotics, phage therapy against AIEC, and nanoparticle-based drug delivery systems for localized anti-inflammatory action. Understanding the mucosa-specific microbiota-metabolite-host interactions is pivotal for advancing precision medicine in IBD, bridging gaps in prior fecal-focused research.

Label-free optical imaging provides non-invasive, high-speed, high-resolution metabolic characterization of live bacteria with single-cell resolution. Here, we demonstrate the ability of label-free multiphoton autofluorescence microscopy to characterize the fast (between 0 and 30 min) metabolic changes in bacteria in response to antibiotic treatments and observe the cell-to-cell metabolic heterogeneity of planktonic bacteria and biofilms. Results indicate that bacteria exhibit a distinct measurable response to bactericidal treatments within seconds. Furthermore, S. aureus biofilms exhibit metabolic heterogeneity, with local pockets of high metabolic activity. Bacteria in biofilms exhibit altered metabolic profiles compared to planktonic bacteria for all four species examined: S. aureus, P. aeruginosa, M. catarrhalis, and S. pneumoniae. These results shed light on the spatial and temporal metabolic heterogeneity of bacteria and the quantification possibilities using label-free nonlinear optical microscopy.