Microbiome research reports最新文献

Aim: The gut microbiota plays a key role in shaping individual responses to drugs, but current tools have limited potential to probe drug-microbe interactions within the complex, individualised gut environment. This study employed bioorthogonal labelling to track and identify gut microbial taxa and molecular mechanisms involved in the bioaccumulation of entacapone, a Parkinson's disease drug. Methods: We synthesised alkyne-tagged derivatives of entacapone and evaluated their suitability as molecular probes in ex vivo incubations with faecal communities or different Escherichia coli (E. coli) strains. Following incubation, tagged drugs were conjugated to a fluorescently labelled azide via click chemistry. Labelled cells were visualised, quantified, sorted via fluorescence-activated cell sorting (FACS), and identified via 16S ribosomal RNA (rRNA) gene amplicon sequencing. Results: Entacapone alkyne derivatives retained the biological activity and effects of the original drug on the microbiota, significantly reducing microbial loads and shifting community composition across the three donors tested. Conjugation of alkyne-entacapone with a labelled azide revealed that between 80% to 96% of all microbial cells in a donor's faecal sample accumulate entacapone. Nearly all taxa detected in incubations were recovered in labelled FACS fractions, confirming widespread uptake of the drug. Finally, we demonstrate that different E. coli strains exhibit varying levels of entacapone accumulation and identify a siderophore transporter that plays a role in this process. Conclusion: Our findings reveal that entacapone is widely bioaccumulated by the gut microbiota across three donors and identify a key molecular mediator of this accumulation. This study expands the toolkit for investigating drug-microbiome interactions and holds significant potential to advance our understanding of drug-microbiome dynamics and therapeutic outcomes.

The gut virome, particularly its viral and phage components, is increasingly recognized as a key modulator of intestinal microbial dynamics in gastrointestinal inflammatory diseases. Beyond well-characterized bacterial dysbiosis, growing evidence suggests that virome alterations contribute to the development and progression of inflammatory bowel disease, metabolic dysfunction-associated steatohepatitis, alcoholic hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, and pancreatitis. As the most abundant viruses in the gut, bacteriophages influence microbial ecosystem stability and host immune responses through lytic and lysogenic interactions with bacterial populations. Amid the growing burden of multidrug-resistant infections and heightened interest in microbiota-based interventions, phage therapy has re-emerged as a viable strategy in both preclinical and translational contexts. This review synthesizes recent insights into bacteriophage dynamics in the context of major gastrointestinal and hepatopancreatic inflammatory diseases, highlighting potential compositional shifts, proposed mechanisms of phage-microbe interactions, and supportive evidence from animal models and early clinical applications. We also discussed the critical challenges that had to be addressed to enable clinical translation, including host range restrictions, resistance and safety concerns, immunogenicity, and delivery limitations, while emphasizing emerging strategies such as phage engineering, encapsulation technologies, and standardized regulatory frameworks.

The gastrointestinal tract is the major ecological niche in which gut microbes interact with epithelial and immune cells to maintain homeostasis in mammals. Moreover, probiotics modulate the gut microbiota and exert various health benefits after oral administration and persistence in the gut. Until now, animal models have been the gold standard for unravelling the mechanisms implicated in host-microbe interactions. However, their translational relevance to clinical trials and the associated ethical concerns underscore the need for alternative models. The emergence of microfluidic organ-on-chip technologies provides promising new alternative models to explore human host-microbe interactions while maintaining the tissue-level complexity and inter-individual variability. In this perspective, we discuss the potential of using mice, non-rodent models and gut-on-chip technologies to better characterize the interactions between the host, the gut microbiota, and orally administered probiotics, and to monitor microbial spatiotemporal dynamics at the tissue level.

Background: Aging may be associated with low-grade chronic inflammation ("inflammaging") and gut microbiome alterations. Dietary polyphenols have been proposed as modulators of these processes. This study aimed to explore the effects of a polyphenol-rich diet (PR-diet) on inflammatory markers, gut microbiota, and metabolomic profiles in subjects aged ≥ 60 years stratified by baseline inflammation levels. Methods: In this post-hoc analysis of the MaPLE (Microbiome mAnipulation through Polyphenols for managing Leakiness in the Elderly) randomized crossover trial, 50 subjects aged ≥ 60 years were categorized into two subgroups: high inflammation (cH) and low inflammation (cL). Participants received a PR-diet or a control diet for 8 weeks, with a washout period in between. Fecal, blood, and urine samples were analyzed using shallow shotgun metagenomics and untargeted metabolomics. Results: The PR-diet was associated with a significant reduction in key inflammatory markers [e.g., interleukin-6 (IL-6), C-reactive protein] in the cH group. Distinct microbial shifts were observed, including an increase in Blautia and Dorea and a modest improvement in microbial diversity in cH subjects. Metabolomic analysis revealed group-specific changes, notably in polyphenol-derived metabolites. Conclusion: These findings suggest that PR-diets may beneficially modulate inflammation and the gut microbial ecosystem in subjects aged ≥ 60 years with elevated baseline inflammation. Stratification by inflammatory status may improve the targeting and personalization of dietary interventions to support healthy aging.

B-group vitamins and vitamin K are essential micronutrients required for numerous cellular processes in both microbial and human physiology. While traditionally considered to originate predominantly from dietary sources, the biosynthetic capacity of the human gut microbiota has recently been recognized as a valuable, though historically underappreciated, endogenous source of these vitamins. In particular, the microbial contribution to the host vitamin pool is increasingly acknowledged as a functionally relevant aspect of vitamin homeostasis, especially in the colon, where microbiota-derived vitamins may be absorbed via specific transport mechanisms. This review provides a comprehensive overview of our current understanding of the biosynthesis of B-group vitamins and vitamin K by human gut-associated bacteria, with particular emphasis on key methodologies employed to assess if, how and to what extent members of the gut microbiota supply their host with such micronutrients. Through an integrated overview of available evidence, we highlight both the progress made and the outstanding challenges in elucidating the microbial contribution to the host vitamin metabolism.

Postoperative insulin resistance (PIR) is a common metabolic complication that significantly affects patient recovery and long-term outcomes. Recent studies have revealed a robust association between the gut microbiota and PIR, underscoring the potential role of microbial communities in modulating insulin sensitivity. In this comprehensive review, we synthesize current literature on the interplay between PIR and the gut microbiota, delve into the underlying mechanisms linking the two, and provide an overview of recent research progress in this field. Evidence suggests that the gut microbiota may influence PIR through mechanisms involving metabolic endotoxins, short-chain fatty acids, branched-chain amino acids, and other metabolites. Overall, the gut microbiota plays a crucial role in the onset and progression of PIR. This review aims to provide a theoretical basis for developing PIR intervention strategies based on microbiome regulation.

The rising prevalence of multidrug-resistant (MDR) bacterial infections, coupled with the diminishing efficacy of antibiotics, has reinvigorated interest in bacteriophage (phage) therapy as a promising alternative, leveraging its unique bactericidal mechanisms and precise targeting capabilities. Concurrently, phage display technology has advanced tumor diagnostics and targeted drug delivery through high-throughput peptide screening. This review systematically evaluates the mechanisms, strategies, and clinical progress of phage-based applications in anti-infective and oncological therapies. Clinical evidence highlights its efficacy against respiratory, oral, wound, bloodstream, and urinary tract infections, alongside solid tumors. However, challenges persist, including limited host range, bacterial resistance, immunogenicity, inefficient delivery systems, and regulatory uncertainties. Future efforts should prioritize AI-driven phage optimization, standardized pharmacokinetic assessment, and interdisciplinary collaboration to accelerate clinical translation. Despite current limitations, phage therapy represents a transformative and scalable approach for combating antimicrobial resistance and advancing precision oncology, positioning it as a pivotal tool in addressing global health crises.

Aim: This study aimed to screen Lactococcus lactis strains with varying gamma-aminobutyric acid (GABA) production and evaluate their effects on intestinal dysfunction and neurobehavioral abnormalities in an irritable bowel syndrome (IBS) mouse model, with a focus on GABAergic signaling and dose-dependent mechanisms. Methods: Three Lactococcus lactis strains were selected based on GABA yield and genetic analysis. IBS was induced in mice via Citrobacter rodentium infection and water avoidance stress. Intestinal integrity, inflammation, histopathology, and behavior were assessed. GABA levels in the colon and serum were measured by liquid chromatography-mass spectrometry (LC-MS). GABA receptor subunit expression in the colon, hippocampus, and amygdala was analyzed via quantitative real-time polymerase chain reaction and Western blotting. Results: GABA-producing strains alleviated intestinal dysfunction in IBS mice by reducing IL-6 gene expression and iNOS activity, upregulating CLDN2, and improving tissue integrity. Anxiety-like behaviors and cognitive deficits were also attenuated. Colonic GABA levels, GABRA13 mRNA, and GABRA3 protein expression increased in a dose-dependent manner, whereas TRPV1 mRNA and TRPV1 protein levels were downregulated. Serum GABA remained unchanged. In the central nervous system, the expression of hippocampal GABA_A and GABA_B receptors was elevated, with both GABRA13 mRNA and GABRA3 protein levels positively correlating with colonic GABA concentrations. GABRA15 expression was upregulated in the amygdala. Conclusion: GABA-producing Lactococcus lactis effectively alleviates IBS-related intestinal dysfunction and neurobehavioral abnormalities by coordinately modulating GABAergic signaling in both the gut and the central nervous system, exhibiting a clear dose-dependent effect across multiple key phenotypes.

Aim: This study provides a comprehensive genomic characterization of Streptococcus oralis CRC211, a novel bacterial strain isolated from colorectal tumor tissue. Methods: Whole-genome sequencing and comparative genomic analyses were performed. Results: The high-quality assembled genome (15.03 Mb, 40.94% guanine-cytosine content) contains 2 prophage regions spanning 160.5 kb, which may facilitate the horizontal transfer of virulence genes. Functional annotation identified 3,674 genes, with significant enrichment in metabolic pathways (amino acid and carbohydrate metabolism) and virulence factors (116 genes in Virulence Factors Batabase), including adhesins and biofilm-associated proteins that likely promote tumor colonization. Comparative genomic analysis revealed that CRC211 shares 92.29% average nucleotide identity with reference Streptococcus oralis strains, while pan-genome analysis demonstrated an open genome structure with 1,222 conserved core genes. In addition, the strain also carries 75 antimicrobial resistance genes, underscoring its potential clinical relevance. Notably, the genomic profile indicates adaptations for nutrient acquisition and immune evasion in the tumor microenvironment. Conclusion: These findings establish CRC211 as a colorectal cancer (CRC)-associated strain with distinct genomic features that may contribute to tumor progression. The study provides critical insights into its possible oncogenic mechanisms and highlights potential applications in mic ases,indels - changerobiota-based diagnostics or therapeutics for colorectal cancer.

The search for sustainable alternatives to antibiotic growth promoters in poultry production has intensified in recent years, driven by global concerns over antimicrobial resistance and consumer demand for safer food systems. Among the probiotic candidates investigated, Bifidobacterium spp. stand out for their well-documented safety, immunomodulatory properties, and ability to enhance gut health. This review provides a comprehensive analysis of the biological roles, delivery strategies, and microencapsulation techniques for Bifidobacterium spp. as probiotics in poultry. Bifidobacteria contribute to poultry health by modulating the gut microbiota, improving intestinal morphology and digestive enzyme activity, and regulating immune responses through cytokine balance and epithelial barrier reinforcement. However, their strict anaerobic metabolism and sensitivity to gastric acid and processing conditions limit their viability during conventional administration. To address these challenges, we examine various administration routes, including oral, in ovo, spray/litter, and cloacal methods, highlighting their practical advantages and constraints. Special attention is given to microencapsulation technologies, such as spray drying, freeze drying, spray chilling, extrusion, and emulsion, which protect bifidobacteria from environmental stress and enhance their delivery to target intestinal sites. By integrating recent advances in biotechnology and delivery systems, this review underscores the potential of Bifidobacterium spp. as functional feed additives in antibiotic-free poultry production. Tailoring encapsulation materials and administration routes to match specific production goals is key to maximizing probiotic efficacy. Continued research on strain performance under commercial conditions will be essential to facilitate their large-scale application in sustainable poultry farming.