npj Biofilms and Microbiomes最新文献

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.

Hepatocellular carcinoma (HCC) is a frequently seen malignant tumor globally. Huaier is the dried fruiting body of the fungus Trametes robiniophila Murr. Huaier granule (HEG), formulated from the Huaier extract, is a Class I innovative anti-cancer drug in China and exhibits significant anti-HCC effects in clinical settings. Nevertheless, the specific mechanisms underlying its efficacy remain incompletely understood. This research demonstrated that HEG effectively suppressed tumor development in the orthotopic HCC mouse model in a gut microbiota-dependent manner and modified the gut microbiota composition. Notably, the primary differential bacterial genera between the Model group and the HEG group included Adlercreutzia. HEG exerted anti-HCC effects by repairing the intestinal barrier, improving colon immunity, and ameliorating the immune microenvironment by suppressing the MAPK signaling pathway via the gut microbiota-gut-liver axis. By integrating 16S rRNA sequencing with metabolomics data, supplemented by literature mining and in vitro validation, Equol, produced by specific gut microbiota Adlercreutzia, was identified as a key metabolite through which HEG exerted its anti-HCC effects by modulating gut microbiota. Moreover, Equol was essential for the anti-HCC effects of HEG. Additionally, Equol ameliorated the immune microenvironment through inhibiting the MAPK signaling pathway, while concurrently inhibiting the growth of HCC cells by inducing the G₀/G₁ phase blockade through suppression of Cyclin E1-CDK2/Rb signaling pathway. This study provided a robust scientific foundation for the clinical use of HEG, with Equol emerging as a promising candidate for HCC treatment.

Emerging evidence underscores the critical role of dietary fiber in maintaining gut homeostasis. While extracellular vesicles (EVs) have recently gained attention as key mediators of host-microbe communication, their functional contribution to fiber deficiency-associated pathologies remains largely unexplored. In this study, we revealed that a fiber-free diet induces significant intestinal inflammatory damage in mice, an effect that can be faithfully reproduced through fecal microbiota transplantation. Importantly, we demonstrated that intestinal epithelial cells-derived EVs from fiber-deprived mice are sufficient to recapitulate the detrimental effects of fiber deficiency. Mechanistic studies revealed enrichment of miR-6240 in these EVs, which targeted the 3'UTR of STAT6 mRNA to suppress its expression. This impairment of STAT6 signaling inhibited M2 macrophage polarization, exacerbating intestinal inflammation. This novel pathway is further validated in primary macrophage adoptive transfer experiments. Our work unveils a previously unrecognized mechanism by which fiber deficiency exacerbates intestinal inflammation through IECs-derived EVs and miR-6240/STAT6-mediated macrophage dysfunction.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide and is increasingly recognized as the outcome of complex host-microbe interactions. Beyond established genetic and environmental drivers, the gut microbiome has emerged as a causal and mechanistic contributor to CRC initiation, progression, and therapy response. This review synthesizes current molecular, ecological, and translational evidence to explain how gut microbial communities reprogram immune, metabolic, neural, and endocrine networks within the tumor microenvironment. CRC-associated dysbiosis is characterized by enrichment of pathobionts such as Fusobacterium nucleatum, pks⁺ Escherichia coli, and enterotoxigenic Bacteroides fragilis, and by loss of protective, short-chain-fatty-acid-producing commensals. These microbes promote carcinogenesis through genotoxin-induced DNA damage, epithelial barrier disruption, metabolic rewiring, and chronic inflammation that collectively sustain immune suppression and tumor growth. Defined mutational signatures from bacterial metabolites, including colibactin, cytolethal distending toxin, and indolimines, now directly link microbial exposures to human cancer genomes. By integrating these findings, this review conceptualizes CRC as a biofilm-structured, microbiome-driven ecosystem disease, where polymicrobial consortia coordinate barrier breakdown, immune evasion, and metabolic cooperation. Finally, we highlight emerging microbiota-targeted strategies, including dietary modulation, pre- and probiotics, postbiotics, bacteriophage therapy, engineered live biotherapeutics, and fecal microbiota transplantation, that translate these insights into precision prevention and therapy. Through this integrative framework, the review aims to reposition the microbiome from a correlative feature to a tractable determinant of CRC pathogenesis and treatment response.

Biofilms are intricately associated with life on Earth, enabling functions essential to human and plant systems, but their susceptibility to spaceflight stressors and functional disruption in space remains incompletely understood. During spaceflight, biofilms have largely been considered as potential infrastructure, life support or infection risks. This review focuses on the prevailing beneficial roles of biofilms in human and plant health, and examines evidence of biofilm adaptability in space environments.

The human gut microbiota is vital for immune function, metabolism, and resistance to pathogens. Soil-transmitted helminths like Trichuris trichiura can disrupt this microbial community, but the extent and functional significance of these disruptions across diverse regions remain unclear. We investigated the impact of T. trichiura infection on gut microbiota composition and function in three endemic regions-Côte d'Ivoire, Laos, and Tanzania-using standardized, high-resolution metagenomic profiling. Our findings reveal consistent depletion of key short-chain fatty acid (SCFA) producers, including Blautia sp. MSJ 9 and Holdemanella biformis, and enrichment of mucin-degrading genera such as Ruminococcus and Bacteroides. These changes coincided with increased microbial utilization of host-derived carbohydrates and destabilization of microbial networks, notably with the emergence of Segatella copri in infected individuals. Although taxa-level responses varied by region, similar trends in SCFA depletion and mucin degradation were observed across sites, pointing to a potentially shared metabolic response to infection. These alterations suggest compromised gut barrier function and immune modulation, potentially promoting parasite persistence. Our results underscore the potential of microbiome-based strategies, such as targeted probiotics or dietary interventions, to support helminth control by restoring microbial balance and improving host resilience.

Defective intestinal epithelial tight junction (TJ) barrier is a key pathogenic factor of inflammatory bowel disease (IBD). Probiotic bacterial upregulation of intestinal TJ barrier has been shown to prevent the development of intestinal inflammation. However, the mechanism of microbe-host interactions responsible for the TJ barrier upregulation remains unclear. This study investigates the molecular mechanisms by which a particular strain of probiotic bacteria, Bifidobacterium bifidum (BB1), upregulates the intestinal epithelial TJ barrier. Using in vitro (filter-grown Caco-2 monolayers) and in vivo (recycling intestinal perfusion in live mice) intestinal epithelial model system, we show that BB1 upregulation of intestinal TJ barrier correlated with an increase in occludin gene activity (occludin promoter activity and occludin mRNA transcription levels) and protein expression, with no changes in other TJ proteins. Occludin knockdown or inhibition of gene transcription prevented the enhancement of the TJ barrier, confirming the essential role of BB1-induced occludin gene activation in TJ barrier enhancement, which was mediated sequentially by BB1 activation of the intestinal epithelial cell TLR-2/TLR-6 complex and IRAK-1 phosphorylation, as well as the apical membrane recruitment of the adapter protein TOLLIP. These findings provide novel mechanistic insight into the microbe-host interactions driving probiotic bacteria upregulation of intestinal TJ barrier.

Alcohol-associated liver disease (ALD), characterized by gut barrier disruption and microbial dysbiosis, is associated with significant depletion of the genus Bifidobacterium in patients, as evidenced by our cohort of 127 subjects. Functional screening revealed B. pseudocatenulatum as a protective strain. In a murine ALD model established with a Lieber-DeCarli ethanol diet, oral administration of B. pseudocatenulatum for 8 weeks ameliorated hepatomegaly, steatosis, and serum transaminase levels. Probiotic intervention restored intestinal barrier function, as indicated by reduced lipopolysaccharide-binding proteins and upregulated tight junction protein expression. Microbiome analysis revealed a mitigation of dysbiosis, with a reduction in pathogenic Escherichia-Shigella and Parabacteroides and an enrichment of beneficial Bifidobacterium and Blautia, concomitant with shifts in lipid metabolism. Mechanistically, B. pseudocatenulatum-derived short-chain fatty acids downregulated the expression of hepatic lipogenic genes (Cd36, Fasn, Accα) and pro-inflammatory cytokines (Il-1β, Ccl2, Tnf-α). These results suggest that B. pseudocatenulatum is a promising probiotic candidate for ALD management.

The use of antibiotic lock therapy (ALT) to protect catheters from infection is still being debated due to its inconsistent effectiveness and the potential risk of promoting antibiotic resistance. Using an in vitro infection model of a pediatric venous access port, we demonstrated that 10 days of continuous therapy eradicates Escherichia coli biofilms in vitro without the emergence of antibiotic resistance. By contrast, an 8-h intermittent therapy used for infected parenteral nutrition patients rapidly selected low-level amikacin-resistant mutants both in vitro and in vivo in a clinically relevant rat model, primarily due to convergent fusA, sbmA, and cpxA mutations. Our findings indicate that intermittent dosing generates pulsed selective pressure, favoring the development of resistance mutants within spatially structured biofilm communities. This suggests that biofilms may act as evolutionary incubators, in which medical interventions could unintentionally influence adaptation outcomes. Furthermore, the low-level resistance developing in treated biofilms may be overlooked in clinical settings and contribute to the selection of high-level resistant mutants. Our study, therefore, underscores that, in addition to dosing, optimizing the timing of antimicrobial treatment could mitigate the emergence of resistance. These principles are applicable beyond catheters to any biofilm-related infections where short-term antibiotic exposure may impact microbial community adaptation.