npj Biofilms and Microbiomes最新文献

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.

Implant-associated infections caused by biofilm-forming bacteria, such as Staphylococcus aureus, remain a major clinical challenge due to their high tolerance to conventional antibiotic therapies. We report a dual-targeted therapeutic strategy that combines a tri-enzymatic cocktail designed to degrade key components of the biofilm matrix (TEC; comprising a DNA/RNA endonuclease, an endo-1,4-β-D-glucanase, and a β-N-acetylhexosaminidase), with vancomycin, both delivered via a thermosensitive poloxamer 407 hydrogel, for localized treatment of S. aureus biofilms. The formulation was evaluated both in vitro, on titanium-adherent biofilms, and in vivo, using a model of tissue cages containing titanium beads implanted in the back of guinea pigs. Animals additionally received intraperitoneal administration of vancomycin alone or combined with rifampicin. In vitro, this formulation enabled sequential drug release, with TEC delivered within the first 24 h and vancomycin for up to 96 h, and achieved >5 Log₁₀ reductions in CFU counts after two applications at 48 h interval. In vivo, biofilm-associated bacterial counts reached the detection limit (100 CFU; >5 Log₁₀ decrease from the initial inoculum) in 75% of implants 1 day post-treatment and remained undetectable in 37.5% of them 5 days post-treatment, with no emergence of resistance. Treatment efficacy was reduced if TEC or vancomycin were omitted in the hydrogel or if rifampicin was not included in the intraperitoneal treatment. Vancomycin in the hydrogel also prevented the emergence of rifampicin resistance. These findings underscore the therapeutic potential of a dual-targeted approach, combining biofilm disruption with local sustained antibiotic release, to improve the management of implant-associated infections.

Microbial communities play a central role in viticulture, influencing wine characteristics (a concept termed microbial terroir). Yet, the individual factors shaping these microbiomes remain poorly understood. We conducted a multi-year, large-scale survey of Swiss vineyards (95 sites, 680 samples), longitudinally sampling 12 sites (within 2.46 km and identical cultivar and rootstock) over three years. Using 16S rRNA gene and internal transcribed spacer (ITS) amplicon sequencing, untargeted metabolomics (GC-MS, LC-MS/MS), environmental monitoring, and sensory data, we disentangled environmental factors associated with community assembly and fermentation dynamics. Topography and climate collectively structured microbiomes but affected soil- and plant-associated communities differently. Berry-associated fungi showed the strongest site-specific signature, enabling machine-learning predictions of microclimatic variation. Climatic factors and berry chemistry selectively favor fermentative yeasts, which are each linked to distinct metabolite and aroma profiles. Plant stress metabolites were further associated with microbial and metabolite composition. Our integrative approach thereby fundamentally advances our understanding of microbial biogeography and terroir in viticulture.

Anxiety and sensory hyperresponsiveness are common in children with autism spectrum disorder (ASD), but effective treatments are lacking. Targeting the microbiota-gut-brain axis is a promising strategy. This open-label pilot study evaluated SCM06, a novel synbiotic designed to target anxiety and sensory hyperresponsiveness, in 30 children with ASD (mean age 8.2 years, 22 males). We assessed symptom improvement, compliance, and safety, and collected stool samples for metagenomics and metabolomic analysis over 12 weeks. SCM06 was safe and well-tolerated, and significant improvements were observed in anxiety, sensory hyperresponsiveness, and abdominal pain. Following SCM06 treatment, increase in Bifidobacterium pseudocatenulatum was associated with improved functional abdominal pain (p = 0.0011, p_{_adj} = 0.054), while the abundances of valeric acid and butyric acid increased (p_{_adj} = 0.004 and p_{_adj} = 0.072). Key microbial species, Coprococcus comes and Veillonella dispar, were candidate mediators of symptom improvements. Further randomised controlled trials are warranted to confirm its clinical efficacy.

Sub-Clinical Necrotic Enteritis (SCNE), caused by toxin-producing Clostridium perfringens, is a major challenge in poultry production. SCNE has traditionally been managed with in-feed antibiotics; however, increasing concerns about the spread of antimicrobial resistance call for antibiotic-free strategies for its control. We recently described an NE control strategy leveraging Limosilactobacillus reuteri probiotic strains genetically engineered to deliver nanobodies against alpha toxin and NetB from C. perfringens in the poultry gut. Here, in a controlled study under SCNE conditions, we found that the engineered strains significantly improved feed conversion ratios and weight gain of broilers, outperforming treatment with either a prophylactic antibiotic or the wild-type probiotic strains. To investigate the systemic factors contributing to these performance differences, we analyzed histomorphometrics of the small intestine, microbial metatranscriptomics of jejunal contents, and gene expression from the jejunum and liver tissues. Our results confirmed the in situ expression of the nanobodies and provided evidence that nanobody delivery mitigates SCNE-associated inflammation in the jejunum and toxin-induced damage in the liver, leading to a more quiescent immune state, lower oxidative stress, and improved growth performance. Our findings demonstrate the potential of probiotic-vectored nanobody delivery as an effective strategy for targeting gut antigens across a range of diseases.

Plants have evolved intricate defense strategies to combat herbivorous insect attacks, including the production of toxic secondary metabolites and the attraction of natural enemies. While bacterial-mediated direct toxicity in plant defenses has been demonstrated, the ecological mechanisms by which plants utilize bacteria to indirectly modulate the behavior of natural enemies remain insufficiently explored. In this study, we observed a significant enrichment of Staphylococcus in the tissues of zucchini Cucurbita pepo following infestation by the cotton-melon aphid Aphis gossypii. These bacteria traced from the damaged plant stems and leaves were subsequently found both in aphids and in their secreted honeydew. Among the four dominant bacterial strains isolated from the honeydew, Staphylococcus sp. markedly promoted oviposition preference in mated female ladybird beetles Propylea japonica. Further investigation identified a volatile organic compound, 4-Isopropylbenzyl alcohol, released by Staphylococcus sp. that stimulated strong antennal responses and attracted P. japonica to lay eggs. Collectively, our findings demonstrate that zucchini plants can employ indirect defense against A. gossypii through the enrichment of specific bacteria, revealing a novel ecological role for bacteria in plant defense and expanding our understanding of complex plant-microbe-insect-natural enemy interactions.