AbstractBackgroundInfants born via Cesarean section (C‐section) often have a distinct gut microbiome and higher risks of atopic and immune‐related conditions than vaginally delivered infants. We evaluated whether a microbiome‐based program could shift gut microbiome composition and improve microbiome‐associated health outcomes in C‐section born infants.MethodsThis open‐label, randomized, controlled trial included full‐term C‐section‐born infants aged 0–3 months, randomized to an intervention (n = 25) or control arm (n = 29). Over 6 months, the intervention arm received two microbiome reports, personalized recommendations based on their microbiome, educational materials, and coaching calls focused on microbiome health. Parents reported health conditions via surveys. Primary outcome: Difference between study arms in relative abundance of key gut microbiome taxa and functional genes. Other outcomes: Changes in a C‐section index—a taxonomy‐based metric comparing C‐section‐associated taxa to vaginally‐associated taxa—and prevalence of atopic conditions.ResultsCompared to controls, the intervention arm had higher Bifidobacterium (p = .025, q = .121) and higher abundance of genes associated with human milk oligosaccharide degradation (e.g., α‐L‐fucosidase, p = .019, q = .046) at timepoint 2. In the intervention arm, the C‐section index decreased to a level similar to vaginally born infants (p = .807, q = .807). At the end of the intervention, atopic dermatitis prevalence was lower in the intervention arm than in controls (odds ratio, 0.17 [95% CI, 0.023–0.723], p = .031).ConclusionA personalized microbiome‐based program can modulate the gut microbiome of C‐section‐born infants and may reduce the risk of atopic conditions (ClinicalTrials.gov: NCT06424691).
Peptide-Guided Nanoparticle Drug Delivery for Cardiomyocytes
Background: Nanoparticles (NPs) have been extensively utilized as a drug delivery system to control the release of therapeutic agents to treat cardiac injuries. However, despite the advantages of utilizing NP-based drug delivery for treating heart diseases, the current delivery system lacks specificity in targeting the cardiac tissue, thus limiting its application. Methods: We created three linear peptides, each consisting of 16–24 amino acids. These peptides were conjugated on the surface of NPs, resulting in the formation of cardiac targeting peptide (CTP)-NPs (designated as CTP-NP1, CTP-NP2, and CTP-NP3). To assess their effectiveness, we compared the binding efficiency of these three CTP-NPs to human and mouse cardiomyocytes. Additionally, we determined their distribution 24 h after injecting the CTP-NPs intravenously into adult C57BL/6J mice. Results: When compared to control NPs without CTP (Con-NPs), all three CTP-NPs exhibited significantly increased binding affinity to both human and mouse cardiomyocytes in vitro and enhanced retention in mouse hearts in vivo. A thorough assessment of the heart sections demonstrated that the binding specificity of CTP-NP3 to cardiomyocytes in vivo was significantly greater than that of Con-NPs. None of the three CTP-NPs were proven to cause cardiomyocyte apoptosis. Conclusions: Biocompatible and safe CTP-NP3 can target the heart via binding to cardiomyocytes. This approach of targeting specific molecules-coated NPs may help in delivering therapeutic compounds to cardiomyocytes for the treatment of heart diseases with high efficacy and low toxicity to other tissues.