npj Biofilms and Microbiomes最新文献

Anorexia nervosa (AN) is associated with profound alterations in gut microbiota and host metabolic profiles. While previous studies have primarily focused on the acute phase of AN, the chronic form, severe and enduring anorexia nervosa (SEAN), remains underexplored in terms of microbiome dynamics. In this study, we characterized gut microbiota composition (via 16S rRNA gene amplicon sequencing), serum and fecal metabolites (via mass spectrometry), and an extensive range of clinical, anthropometric, biochemical, and psychiatric parameters in females with acute AN, SEAN, and in healthy controls. SEAN patients exhibited higher antidepressant usage and greater lifetime stress exposure. Acute AN patients presented with more pronounced eating disorder severity and depressive symptoms. Elevated levels of intestinal fatty acid-binding protein in SEAN patients suggest mucosal damage. Microbiota analysis revealed reduced alpha diversity and distinct community composition in both AN groups, with SEAN showing the greatest interindividual variability. Both AN cohorts exhibited significantly lower serum and fecal γ-aminobutyric acid (GABA) levels, which were negatively correlated with taxa such as Christensenellaceae, Ruminococcaceae, and Escherichia-Shigella, i.e., microorganisms potentially associated with GABA degradation or impaired synthesis. Additionally, reductions in short-chain fatty acids suggest impaired microbial fermentation and dysregulation of the gut-brain axis. Collectively, these findings reveal progressive, functionally relevant changes in microbiota-host interactions in SEAN. These alterations likely reflect the persistent disease state and may contribute to its continuation.

Inflammatory bowel disease (IBD) is closely related to changes in the gut microbiota, with proton pump inhibitors (PPIs) possibly playing a role. PPIs use is associated with altering gut microbiota and potentially influencing IBD onset and progression. This review explores the mechanisms by which PPIs affect gut microbiota and IBD, suggests strategies to mitigate dysbiosis, outlook on the causal relationship validation between PPIs use and IBD risk, emphasizing the broader impact of acid suppressants on gut health.

Urolithins are a class of bioactive metabolites derived from the metabolism of dietary ellagitannins by the human gut microbiota. In the gut, urolithins are dehydroxylated regioselectively based on microbiota composition and activity. A single 9-hydroxy urolithin dehydroxylase (ucd) operon in gut resident Enterocloster species has been described to date; however, most enzymes in the urolithin metabolic pathway remain uncharacterized. Here, we investigate urolithin cross-feeding between members of the gut microbiota and discover a novel urolithin dehydroxylase in a subset of Enterocloster species. We show that urolithin intermediates, released by gut resident Gordonibacter species during ellagic acid metabolism, are dehydroxylated at both the 9- and 10-positions by E. asparagiformis, E. citroniae, and E. pacaense, but not E. bolteae. Using untargeted proteomics, we uncover a 10-hydroxy urolithin dehydroxylase operon, termed uxd, responsible for these species-specific differences in urolithin metabolism. By inducing uxd expression with diverse urolithins, we show that 9-hydroxy urolithins are required for uxd transcription and 10-position dehydroxylation. Collectively, this study reveals some of the genes, proteins, and substrate features underlying differences in urolithin metabolism by the human gut microbiota.

α-melanocyte-stimulating hormone (α-MSH) is an anorexigenic peptide. In this exploratory study, a targeted proteomic approach was used to detect α-MSH-like bacterial proteins in the gut microbiota of patients with anorexia nervosa (AN) and healthy controls. Enterobacteriaceae chaperone DnaK was identified as an α-MSH-like protein common to both study groups, while caseinolytic protease B (ClpB) was present in patients with AN. These data further link anorexigenic ClpB to the AN pathophysiology.

Polymicrobial biofilms are acknowledged as evolutionary hotspots; however, the influence of interspecies interactions on adaptive processes remains ambiguous. Using custom-engineered 3D-printed flow systems, biofilms were grown over an 18-day period to explore the evolutionary dynamics over time between two competing species, Pseudomonas defluvii and Pseudomonas brenneri, within communities of differing complexity, using whole-population and whole-genome sequencing methodologies. P. defluvii demonstrated significant phenotypic and genetic diversification in simple biofilms, yet this variation was reduced in complex biofilms, implying that interspecies interactions constrained its adaptation. In contrast, P. brenneri exhibited negligible evolutionary changes irrespective of the diversity present. Genomic analysis correlated the adaptation of P. defluvii with biofilm regulation and chemotaxis. The co-culture with evolved strains indicated that the variants of P. defluvii outperformed their ancestral forms, while P. brenneri remained unchanged. These results show that while the biofilm lifestyle generally fosters adaptive evolutionary processes, interspecies diversity can restrict diversification in a manner specific to each species. This study provides novel insights into the evolution of bacteria within complex biofilm environments, with implications for understanding microbial behavior in both clinical and industrial settings.

Recurrent urinary tract infections (rUTIs) are a major clinical challenge, and their increasing prevalence underscores the need to define host-microbiome interactions underlying susceptibility. How the urinary microbiota engages with the biochemical environment of the urogenital tract is yet to be fully defined. Here, we leverage paired metagenomic and quantitative metabolomic data to establish a microbe-metabolite association network of the female urinary microbiome and define metabolic signatures of rUTI. We observe unique metabolic networks of uropathogens and uroprotective species, highlighting potential metabolite-driven ecological shifts influencing rUTI susceptibility. We find distinct metabolites associated with urinary microbiome diversity and identify a lipid signature of active rUTI that accurately distinguishes our cases from controls. Finally, we identify deoxycholic acid as a prognostic indicator for UTI recurrence. Together, these findings provide insight into microbiome-metabolite interactions within the female urinary tract and highlight potential biomarkers for the development of new diagnostic tools to improve patient outcomes.

Bifidobacterium spp. are representative species of the infant gut microbiome. Human milk oligosaccharides (HMOs) are complex carbohydrates in breast milk, guiding gut microbiome assembly by establishing complex microbial interactions. Here, a synthetic community of seven infant gut microbes was subjected to single species dropouts in bioreactors using three HMOs. Substrate use, acid production, biomass, and metatranscriptomics revealed that B. bifidum was critical for degradation product formation and supporting cross-feeding. Removing B. longum subsp. infantis, known for intracellular HMO use, accelerated global growth and HMO consumption, suggesting competitive interactions. Some dropouts led to the accumulation of sialic acid, fucose, or lactose. Metatranscriptomics showed niche expansion, upregulated central metabolism and cross-feeding dependencies when certain species were removed. Modeling highlighted that HMO degradation rates strongly influence community dynamics. Overall, this study identifies key ecological roles in infant gut microbes and deepens our understanding of how HMOs shape microbiota assembly and function.

Acute pancreatitis (AP) is a complex gastrointestinal disorder associated with disruptions in the gut microbiome. However, the gut microbial and metabolomic profiles in recurrent acute pancreatitis (RAP), which is a clinically distinct subtype of AP, remain unclear. This study integrated microbiome-metabolome analysis to identify the key gut microbial species and metabolic pathways associated with RAP. The findings reveal that the abundance of Faecalibacterium prausnitzii (Fp) is significantly diminished in RAP patients, exhibiting a strong negative correlation with disease severity. Consistent with this observation, fecal microbiota transplantation enriched with Fp significantly ameliorated pancreatic injury in RAP mice. We further isolated Fp Ai 3-16 strain from the stool of healthy volunteers. Functional validation using experimental AP models demonstrates that Fp Ai 3-16 and its metabolite oleic acid (OA) can effectively attenuate pancreatitis by modulating MAPK/NF-κB signaling pathways and restoring the intestinal Th17/Treg balance. Importantly, these results extend beyond the context of RAP, as they highlight the broader significance of the gut-pancreas axis in the pathogenesis of AP. Thus, the elucidation of the underlying molecular mechanisms offers novel therapeutic avenues for RAP management and provides a foundation for further investigations into the intricate interplay between the gut microbiome and the pancreas.

Osteomyelitis, an infection of bone, is traditionally treated with long-term, systemic, high-dose antibiotics, which can lead to kidney and liver damage and accelerate the development of antibiotic resistance. Localized delivery may mitigate these risks by delivering antimicrobial(s) directly to the site of infection. Herein, innately antimicrobial chitosan hydrogel (CH) containing polylactic acid (PLA) microparticles, each loaded with fosfomycin antibiotic, was used to combat a biofilm-forming strain of Staphylococcus aureus. This dual CH + PLA biomaterial treatment mitigated S. aureus in planktonic and biofilm form in vitro, and in a clinically relevant, implant-associated rat model of chronic osteomyelitis. Notably, only the CH + PLA biomaterial treatment led to a reduction in bone defect area, plasma haptoglobin level, and bacterial burden in bone and soft tissue, compared to hydrogel only. Local treatment of osteomyelitis with the chitosan+microparticle vehicle loaded with fosfomycin mitigated S. aureus pathogenesis and may serve as an effective alternative to systemic antibiotics.

Using multi-omics tools, we discovered new antimicrobial peptides (AMPs) and examined AMP-microbial interactions in three Appalachian salamander species (Plethodon cinereus, Eurycea bislineata and Notophthalmus viridescens). We conducted skin transcriptomics (n = 13) and proteomics (n = 91) to identify 200+ candidate AMPs. With candidate AMPs, we identified correlations with skin microbiomes and synthesized 20 peptides to challenge against pathogens of amphibians (Batrachochytrium dendrobatidis: Bd) and humans (ESKAPEE). Using transcriptomics, candidate AMPs were detected in all individuals with Cathelidicins being most common. Using proteomics, AMPs were found in 34% of individuals (31/91)-predominately E. bislineata-with Kinin-like peptides being most common. Candidate AMP composition generally predicted skin bacterial composition, suggesting that AMPs influence host-microbial symbioses. Crude and synthesized peptides showed limited activity against Bd. Two synthesized Cathelicidins (Pcin-CATH3 and Pcin-CATH5) inhibited human pathogens, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli. Our findings inform the potential usage of AMPs in conservation and translational applications.