npj Biofilms and Microbiomes最新文献

Cholestasis, a bile flow disorder common to many liver diseases, currently lacks effective treatments. Emerging evidence links gut microbiota disturbances to cholestatic liver injury. Here, an antibiotic cocktail (ABX)-treated mouse model confirmed the indispensable role of the intestinal microbiota, with marked shifts including increased Alistipes putredinis (A. putredinis) and decreased Clostridium spp. (C. spp.). In vitro, ferulic acid and wogonin effectively modulated the gut flora, and in vivo they alleviated liver injury. Administration of A. putredinis exacerbated hepatic inflammation by disrupting intestinal barrier integrity and facilitating bacterial translocation, an effect reversed by ferulic acid. Conversely, treatment with C. spp. and wogonin enhanced bile salt hydrolase activity and bile acid excretion. Notably, combined treatment with ferulic acid and wogonin or C. spp. significantly ameliorated cholestatic liver injury. These findings underscore the critical role of gut microbiota in cholestasis and suggest therapeutic potential for microbiota-targeted and natural compound-based interventions.

Tolerance to antimicrobial agents in mature and structured biofilms presents a significant challenge in clinical and industrial applications. The contribution of biofilm physical structure to antimicrobial tolerance remains particularly poorly understood, primarily due to the lack of biofilm structure quantification and manipulation studies. To fill the gap in our knowledge, we have investigated how mechanical and biochemical disruptions of biofilm integrity affect Bacillus subtilis tolerance to antimicrobial agents. Our findings reveal that biofilm structural integrity is a major determinant of tolerance to membrane disrupting antibiotic daptomycin. Biofilm viscoelastic properties as well as antimicrobial tolerance to daptomycin were directly related to the presence of exopolysaccharide EpsA-O. In the absence of EpsA-O bacteria produced weak biofilms with markedly reduced elastic and viscous moduli that correlated with a 3-log reduction in bacterial survival rate when challenged with daptomycin. These findings underscore the protective role of biofilm structure against antibiotics and suggest that targeting biofilm structural integrity could substantially enhance antimicrobial treatment strategies for biofilm-related infections.

Respiratory viral co-infections in children with Mycoplasma pneumoniae pneumonia (MPP) are common and cause severe clinical manifestations. However, the exact pathogenic mechanisms of MPP co-infections are still unclear. In this study, we conducted a large-scale clinical analysis of 3106 MPP patients to characterize co-infection patterns. Subsequent metabolomics, microbiomics, and cytokines analyses of the bronchoalveolar lavage fluid from 73 MPP cases were performed. Patients were divided into groups with single Mycoplasma pneumoniae (MP) infection and co-infection (including co-adenovirus [co-ADV] and co-influenza A virus [co-IAV]), while bronchial foreign body patients served as controls. Metabolomic profiling identified 616 differential metabolites between the single MP group and the co-infection group. Collectively, these metabolites contributed to the formation of a pro-inflammatory microenvironment in patients with co-infections. Notably, ADV co-infection induced profound pulmonary microbiota dysbiosis, characterized by selective depletion of Lactobacillus. Next, we observed a robust upregulation of CCL-family chemokines in patients co-infected with ADV, which showed a significant correlation with peripheral monocyte counts, suggesting that monocyte-driven inflammation may serve as a key mechanism for disease exacerbation. These findings demonstrate that co-infection (co-ADV and co-IAV) triggers a pro-inflammatory metabolic shift. Additionally, ADV co-infection specifically disrupts lung microbiota structure and increases CCL family chemokines.

Staphylococcus aureus is capable of colonizing diverse environments and forming biofilms. In this study, we found that the knockout of NO synthase (NOS) impaired biofilm integrity, resulting in weakened biofilms. We found the deletion of the nos reduced intracellular NO levels, which subsequently altered the S-nitrosylation modification levels of the proteome. This alteration was particularly pronounced in the S-nitrosylation modification of the cysteine residue at position 12 of the MgrA. This modification reduced the binding affinity of MgrA to the promoter of the acetyltransferase gene (icaA), resulting in reduced levels of poly-N-acetyl-β-(1-6)-glucosamine (PIA), a key component of biofilms formed by S. aureus, thereby further weakening biofilm formation. Consequently, we conclude that NOS in S. aureus S-nitrosylates the MgrA through the synthesis of endogenous NO. This process strengthens the interaction between MgrA and the icaA promoter (P_icaA), thereby enhancing the synthesis of major polysaccharides in biofilms and promoting biofilm formation.

Fungus-growing ants maintain an ectosymbiotic microbial garden, an intertwined mesh of fungal symbiont hyphae and microbiota growing through plant substrates. Here, we investigate how different plant diets influence the garden lignocellulosic profile, and whether the microbiota respond to dietary changes. Colonies of Atta sexdens were provided with four different dietary regimens, varying in fiber composition and nutritional content. Diet changed the garden lignocellulosic profile, also influencing the microbial taxonomic composition. The diet of only leaves enriched the garden in Bacillus and Weissella, while a diet of only fruits/cereals lead to a Carnimonas and Mesoplasma enrichment; diets mixing leaves and fruits/cereals intermittently and alternatively enriched the garden in Bacillus, Mesoplasma, and Weissella. The fungal crop development and the spatial distribution of the microbiota and biofilm also varied according to the diet. Our findings suggest that diet has a pivotal role in determining whether ant colonies function optimally and remain healthy.

The adaptation to low temperature has research value in the fields of spaceflight, disease treatment, and ecological evolution. However, continuous exposure to cold leads to hypothermia and death in homothermic animals. Interestingly, heterothermic animals can easily overcome this challenge. We transferred intestinal bacteria from hibernating Marmota himalayana into mice (homothermic animals) and successfully induced a torpor-like state. The mice exhibited typical characteristics of hibernation (torpor-like), such as the rectal temperature decreased by 3.72-4.58 °C, respiration rate and physical activity were down-regulated, and heat was concentrated in the brown adipose tissue. Those was associated with the Sphingolipid metabolism, regulated by Bacteroides, opened the temperature switch in the medial preoptic area and ventromedial hypothalamus through the "gut-brain axis". Our findings suggested that gut bacteria can regulate thermoregulation via the gut-brain axis and induce animals to adapt to low temperatures in a torpor-like state.

Dietary restrictions like alternate-day fasting (ADF) can counteract several age-related disorders, but its role in Parkinson's disease (PD) is still controversial. Recent findings highlight the imbalances in the gut-brain axis in PD, herein, we aim to study whether ADF can confer protection in PD mice through the gut-brain axis. Firstly, we assessed the neuroprotective effect of ADF in a time-dependent manner and found that 16 -week ADF could confer the optimal neuroprotection by preserving dopaminergic neurons and reducing the level of α‑synuclein (α‑syn) in the substantia nigra (SN), and it could decrease inflammatory cytokine levels in both the brain and the gut. Furthermore, ADF reshaped gut microbial composition and altered metabolites associated with PD. Relative abundances of several intestinal flora, including Alistipes, Helicobacter and Lactobacillus, were identified as potential mediators. In addition, we conducted fecal microbiota transplantation (FMT) to further investigate the role of the gut-brain axis in the neuroprotective effects of ADF. Notably, we found that FMT from ADF mice conferred equal protection to ADF in ameliorating the pathology and inflammation in both the brain and the gut. Collectively, our findings suggest that the microbiota-gut-brain axis is crucial to the neuroprotective effect of ADF in PD.

Replacing implanted medical hardware due to infection often requires one or more revision surgeries. Each surgery triggers a tissue injury response and disrupts the established bacterial biofilm. However, the complex tissue response to reinjury and biofilm disturbance is not well understood. Our results show that with an existing infection, immunological niches such as the bone marrow, lymph nodes, and circulating blood further upregulate pro-inflammatory programs in response to revision. Rather than reducing bacterial burden, this heightened inflammation provokes virulence factor expression and tissue damage, including bone osteolysis and muscle fibrosis. While muscle fibrosis appears transient and begins resolving by 14 days post-revision, osteolysis continues to progress. This study defines the timing and pathophysiology of coordinated multi-tissue responses to revision during infection. Understanding how host-pathogen interactions influence tissue recovery after revision can help identify risks and guide interventions that minimize damage and maximize bacterial clearance.

The viromes of maternal peripheral blood (MPB) and umbilical cord blood (UCB) provide crucial insights into mother-to-infant transmission and the associations of maternal health with early-life viral colonization. Using viral metagenomic sequencing of 433 MPB and 426 UCB samples, we assembled 57 near-complete genomes from four core viral families (Anelloviridae, Circoviridae, Parvoviridae, Flaviviridae). MPB viromes were primarily composed of bacteriophages and Anelloviridae, while UCB exhibited relatively increased abundances of Parvoviridae and Human Endogenous Retroviruses. Maternal disease correlated with reduced α-diversity in MPB but elevated richness in UCB. β-Diversity varied significantly with both health status and sample type. Differential abundance analysis identified health-specific signatures, including enriched Parvoviridae in diseased UCB. Phylogenetic evidence indicated possible vertical transmission and high genetic diversity among identified viruses. This study systematically characterizes the maternal-fetal blood virome and reveals associations between maternal health status and viral community structure, providing a basis for understanding early-life viral exposure and informing future preventive strategies.

The association between gut microbiota and acute kidney injury (AKI) has garnered increased attention recently. Herein, we investigated the effect of the gut microbiota and its metabolites on regulating AKI-associated kidney injury and inflammation. We observed that Clostridium scindens (CS) can ameliorate ischemia/reperfusion injury/folic acid-induced renal dysfunction, oxidative stress, and inflammation, and enhance intestinal barrier function. Mechanistically, CS can facilitate indole-3-acetic acid (IAA) production via the tryptophan metabolic pathway: tryptophan-indole-3-pyruvic acid-IAA. The increased intestinal IAA activates the aryl hydrocarbon receptor to restore intestinal barrier integrity and decreases interferon-γ influx into the bloodstream, thereby alleviating renal inflammation. The natural product Nobiletin ameliorated AKI by promoting CS growth. Our findings suggest that regulating CS is a promising approach for treating AKI.