npj Biofilms and Microbiomes最新文献

Biofilms constitute one of the most common forms of living matter, playing an increasingly important role in technology, health, and ecology. While it is well established that biofilm growth and morphology are highly dependent on the external flow environment, the precise role of fluid friction has remained elusive. We grew Bacillus subtilis biofilms on flat surfaces of a channel in a laminar flow at wall shear stresses spanning one order of magnitude (τ_w = 0.068 Pa to τ_w = 0.67 Pa). By monitoring the three-dimensional distribution of biofilm over seven days, we found that the biofilms consist of smaller microcolonies, shaped like leaning pillars, many of which feature a streamer in the form of a thin filament that originates near the tip of the pillar. While the shape, size, and distribution of these microcolonies depend on the imposed shear stress, the same structural features appear consistently for all shear stress values. The formation of streamers occurs after the development of a base structure, suggesting that the latter induces a secondary flow that triggers streamer formation. Moreover, we observed that the biofilm volume grows approximately linearly over seven days for all shear stress values, with a growth rate inversely proportional to the wall shear stress. We develop a scaling model, providing insight into the mechanisms by which friction limits biofilm growth.

Biofilms are critical for understanding environmental processes, developing biotechnology applications, and progressing in medical treatments of various infections. Nowadays, a key limiting factor for biofilm analysis is the difficulty in obtaining large datasets with fully annotated images. This study introduces a versatile approach for creating synthetic datasets of annotated biofilm images with employing deep generative modeling techniques, including VAEs, GANs, diffusion models, and CycleGAN. Synthetic datasets can significantly improve the training of computer vision models for automated biofilm analysis, as demonstrated with the application of Mask R-CNN detection model. The approach represents a key advance in the field of biofilm research, offering a scalable solution for generating high-quality training data and working with different strains of microorganisms at different stages of formation. Terabyte-scale datasets can be easily generated on personal computers. A web application is provided for the on-demand generation of biofilm images.

Sebaceous free fatty acids are metabolized by multiple skin microbes into bioactive lipid mediators termed oxylipins. This study investigated correlations between skin oxylipins and microbes on the superficial skin of pre-pubescent children (N = 36) and adults (N = 100), including pre- (N = 25) and post-menopausal females (N = 25). Lipidomics and metagenomics revealed that Malassezia restricta positively correlated with the oxylipin 9,10-DiHOME on adult skin and negatively correlated with its precursor, 9,10-EpOME, on pre-pubescent skin. Co-culturing Malassezia with keratinocytes demonstrated a link between 9,10-DiHOME and pro-inflammatory cytokines IL-1β and IL-6 production. We also observed strong correlations between other skin oxylipins and microbial taxa, highlighting life stage differences in sebum production and microbial community composition. Our findings imply a complex host-microbe communication system mediated by lipid metabolism occurring on human skin, warranting further research into its role in skin health and disease and paving the way towards novel therapeutic targets and treatments.

Biofilms are critical in the persistence of Pseudomonas aeruginosa infections, particularly in cystic fibrosis patients. This study explores the adaptive mechanisms behind the phenotypic switching between Small Colony Variants (SCVs) and revertant states in P. aeruginosa biofilms, emphasizing hypermutability due to Mismatch Repair System (MRS) deficiencies. Through experimental evolution and whole-genome sequencing, we show that both wild-type and mutator strains undergo parallel evolution by accumulating compensatory mutations in factors regulating intracellular c-di-GMP levels, particularly in the Wsp and Yfi systems. While wild-type strains face genetic constraints, mutator strains bypass these by accessing alternative genetic pathways regulating c-di-GMP and biofilm formation. This increased genetic accessibility, driven by higher mutation rates and specific mutational biases, supports sustained cycles of SCV conversion and reversion. Our findings underscore the crucial role of hypermutability in P. aeruginosa adaptation, with significant implications for managing persistent infections in clinical settings.

Indoxyl sulfate (IS) has been implicated in the pathogenesis of cardiovascular diseases. IS is converted from indole, a metabolite of dietary tryptophan through the action of gut microbial tryptophanase, by two hepatic enzymes: CYP2E1 and SULT1A1. We hypothesized that the effect of tryptophan intake on IS production might differ from person to person. We enrolled 72 healthy persons (33 ± 7 years; 54.2% women) to undergo an oral tryptophan challenge test (OTCT), in which 7 blood samples were collected at 0, 4, 8, 12, 24, 36, and 48 h following oral administration of L-tryptophan 2000 mg. We observed high interindividual variability of IS production in the response to an OTCT. Twenty-four subjects in the lowest tertile of the baseline-adjusted area under the curve of IS were defined as low-IS producers, whereas 24 subjects in the highest tertile were defined as high-IS producers. There was no significant difference in baseline characteristics or CYP2E1 and SULT1A1-SNP genotyping distributions between the two IS-producing phenotypes. However, distinct differences in gut microbial composition were identified. In addition, the abundance of tryptophanase was significantly higher in the high-IS producers than in the low-IS producers (P = 0.01). The OTCT may serve as personalized dietary guidance. High-IS producers are more likely to be at greater risk of cardiovascular diseases and may benefit from consuming foods low in tryptophan. Potential clinical applications of the OTCT in precision nutrition warrant further investigation.

The oral-gut microbiota axis plays a crucial role in cardiometabolic health. This review explores the interactions between these microbiomes through enteric, hematogenous, and immune pathways, resulting in disruptions in microbial balance and metabolic processes. These disruptions contribute to systemic inflammation, metabolic disorders, and endothelial dysfunction, which are closely associated with cardiometabolic diseases. Understanding these interactions provides insights for innovative therapeutic strategies to prevent and manage cardiometabolic diseases.

Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted in a significant reduction in atherosclerosis burden in conventionally raised (ConvR) Apolipoprotein E (ApoE) knockout (KO) mice but not in germ-free (GF) ApoE KO mice. Metabolomic analysis revealed that consumption of quercetin significantly increased plasma levels of benzoylglutamic acid, 3,4 dihydroxybenzoic acid (3,4-DHBA) and its sulfate-conjugated form in ConvR mice, but not in GF mice supplemented with the flavonoid. Levels of these metabolites were negatively associated with atherosclerosis burden. Furthermore, we show that 3,4-DHBA prevented lipopolysaccharide (LPS)-induced decrease in transendothelial electrical resistance (TEER). These results suggest that the effects of quercetin on atherosclerosis are influenced by gut microbes and are potentially mediated by bacterial metabolites derived from the flavonoid.

We have previously demonstrated that subgingival levels of nitrate-reducing bacteria, as well as the in vitro salivary nitrate reduction capacity (NRC), were diminished in periodontitis patients, increasing after periodontal treatment. However, it remains unclear if an impaired NRC in periodontitis can affect systemic health. To determine this, the effect of nitrate-rich beetroot juice (BRJ) on blood pressure was determined in 15 periodontitis patients before and 70 days after periodontal treatment (i.e., professional mechanical plaque removal, oral hygiene instruction, and subgingival instrumentation), as well as in a healthy control group of 15 individuals. Additionally, subgingival and tongue samples were taken to analyse the bacterial composition with Illumina sequencing of the 16S rRNA gene. In healthy individuals, the systolic and diastolic blood pressure (SBP and DPB) decreased significantly (both P < 0.01) 90 min after BRJ intake, but not in periodontitis patients. However, after periodontal treatment, this blood pressure-lowering effect was recovered (P < 0.05 for SBP; P < 0.01 for DBP). Lower levels of salivary nitrate after identical doses of BRJ intake indicated a potentially higher NRC in healthy individuals (P < 0.05). Periodontitis-associated bacteria decreased in tongue and subgingival samples after periodontal treatment (P < 0.01). In contrast, nitrate-reducing bacteria were associated with health in both habitats, but increased only in subgingival plaque after periodontal treatment (P < 0.001). This is the first study showing that periodontitis could limit the blood-pressure lowering effects of nitrate reduction by the oral microbiota. We propose that an impaired NRC represents a potential link between periodontitis and systemic conditions, which should be confirmed in future randomized controlled trials. Future work should also aim to determine if nitrate prebiotic supplementation and/or tongue cleaning could improve the treatment of periodontitis and its associated comorbidities.

The human body houses many distinct and interconnecting microbial populations with long-lasting systemic effects, where the oral cavity serves as a pathogens' reservoir. The correlation of different disease states strongly supports the need to understand the interplay between the oral tissue niche and microbiome. Despite efforts, the recapitulation of gingival architecture and physiological characteristics of the periodontal niche has yet to be accomplished by traditional cultural strategies. Here, we are showing for the first time the investigation of host-microbiome interactions in healthy conditions within a human oral tissue model over seven days. Our results indicated long-term host and microbiome viability, host barrier integrity, phenotypic functional response, and preservation of healthy microbial populations and interbacterial dialogs. This in vitro platform can maintain tissue homeostasis at the interface of the periodontal niche, thus, offering opportunities to identify predictive disease biomarkers and to develop intervention strategies to promote oral and overall health.

This study aims to evaluate differences in gut microbiota structures between infertile women undergoing frozen embryo transfer (FET) with gestational diabetes mellitus (GDM) and healthy controls (HCs), and to identify potential markers. We comprehensively enrolled 193 infertile women undergoing FET (discovery cohort: 38 HCs and 31 GDM; validation cohort: 85 HCs and 39 GDM). Gut microbial profiles of the discovery cohort were investigated during the pre-pregnancy (Pre), first trimester (T1), and second trimester (T2). The microbial community in the HCs group remained relatively stable throughout the pregnancy, while the microbial structure alteration occurred in the GDM group during T2. A model based on ten bacteria and ten metabolites simultaneously was used to predict the risk of GDM developing in the pre-pregnancy state with the ROC value of 0.712. Algorithms on the basis of marker species and biochemical parameters can be used as effective tools for GDM risk evaluation before pregnancy.