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The gut microbiome plays a crucial role in maintaining intestinal homeostasis and influencing immune-mediated diseases. Human faecal microbiota transplantation (FMT) is often employed in murine models to investigate the role of human microbes in disease regulation, but methods for effective colonisation require refinement. This study aimed to assess the colonisation efficiency of human microbiota in a murine model using FMT with human faeces, focusing particularly on the impact of gut microbiota depletion via polyethylene glycol (PEG) and comparing oral-gastric gavage with enema administration routes. Our findings revealed that PEG-induced depletion enhanced human microbiome colonisation in mice. Oral-gastric gavage prolonged colonisation, while enema administration facilitated quicker resolution of dysbiosis, both inducing selective human microbial colonisation in a time-dependent manner. Notably, genera such as Bacteroides, Blautia, Medicaternibacter and Bifidobacteria were successfully colonised, whereas Roseburia, Anaerostipes, Anaerobutyricum and Faecalibacterium failed to establish in the murine gut post-FMT. These findings highlight the challenges of replicating human gut microbiota in murine models and underscore the importance of selecting appropriate FMT methods based on desired outcomes. This study provides valuable insights into the colonisation dynamics of human microbiota in mice, contributing to the development of more effective FMT strategies for disease treatment.
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http://dx.doi.org/10.1111/1751-7915.70173 | DOI Listing |
JCI Insight
September 2025
Edinburgh Medical School: Biomedical Sciences & Euan MacDonald Centre for M, University of Edinburgh, Edinburgh, United Kingdom.
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein. Several therapeutic approaches boosting SMN are approved for human patients, delivering remarkable improvements in lifespan and symptoms. However, emerging phenotypes, including neurodevelopmental comorbidities, are being reported in some treated SMA patients, indicative of alterations in brain development.
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September 2025
Department of Pharmacology, University of Michigan, Ann Arbor, United States of America.
Cardiac hypertrophy is a common adaptation to cardiovascular stress and often a prelude to heart failure. We examined how S-palmitoylation of the small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), impacts cardiomyocyte stress signaling. Mutation of the cysteine-178 palmitoylation site impaired activation of Rac1 when overexpressed in cardiomyocytes.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
School of Medicine, Chongqing University, Chongqing 400044, China.
Engineering functional exosomes represents a cutting-edge approach in biomedicine, holding the promise to transform targeted therapy. However, challenges such as achieving consistent modification and scalability have limited their wider adoption. Herein, we introduce a universal and effective strategy for engineering multifunctional exosomes through cell fusion.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug De
Proliferative retinopathy is a leading cause of irreversible blindness in humans; however, the molecular mechanisms behind the immune cell-mediated retinal angiogenesis remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced retinopathy (OIR) model, we identified an enrichment of sorting nexin (SNX)-related pathways, with SNX3, a member of the SNX family that is involved in endosomal sorting and trafficking, being significantly upregulated in the myeloid cell subpopulations of OIR retinas. Immunostaining showed that SNX3 expression is markedly increased in the retinal microglia/macrophages of mice with OIR, which is mainly located within and around the neovascular tufts.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
MS4A4A belongs to the MS4A tetraspan protein superfamily and is selectively expressed by the monocyte-macrophage lineage. In this study, we aimed to evaluate the role of MS4A4A+ macrophages in rheumatoid arthritis (RA) pathogenesis and response to treatment. RNA sequencing and immunohistochemistry of synovial samples from either early treatment-naïve or active chronic RA patients showed that MS4A4A expression positively correlated with synovial inflammation.
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