Oral lysozyme restores healthy microbiota & combats vascular aging

A study reveals that lysozyme (LYZ) plays a pivotal role in age-related blood vessel inflammation by influencing gut bacteria. It shows that administering LYZ orally can restore a healthy gut balance and reverse signs of vascular aging, whereas administering it directly into the bloodstream can exacerbate these signs. This work addresses age-related inflammation in vessels, a driver of common diseases in older adults.

Linking Gut Health and Vascular Aging: A New Therapeutic Angle

Vascular aging underlies many common conditions in older adults, such as hypertension, atherosclerosis, and kidney disease. Understanding a modifiable factor that links gut health and vessel inflammation could open new, non-invasive approaches to slow or reverse vascular aging. For the medical and biotech industries, it points to gut-targeted interventions—such as oral LYZ supplements, probiotics, or dietary strategies—as potential therapies. For scientists, the work highlights a novel “gut–vascular inflammatory aging axis” and identifies the PI3K–Akt signaling pathway as a key mediator, suggesting new lines of research into metabolites and microbial strains that could benefit vascular health.

Lysozyme Deficiency Drives Vascular Aging via Gut Dysbiosis

Bioinformatic analysis revealed elevated LYZ in human vascular aging and aged mouse models. Lyz1^−/− mice exhibited vascular aging features, including oxidative stress, endothelial dysfunction, DNA damage, senescence, and inflammation, and displayed gut dysbiosis characterized by a reduction in Bifidobacterium and key metabolites. Transcriptomics revealed suppressed PI3K–Akt signaling in their vessels. Microbiota depletion, achieved through the use of antibiotics or germ-free conditions, recapitulated these aging phenotypes and PI3K–Akt suppression. Oral LYZ restored gut balance and reversed vascular aging markers, whereas intravenous LYZ worsened outcomes.

“This work identifies LYZ as both a marker and modulator of vascular aging through its impact on gut bacteria and the PI3K–Akt signaling pathway. The finding that oral—but not intravenous—LYZ can restore beneficial gut bacteria and improve vessel health in aging models suggests a practical route for future therapies,” said Prof. Tianhao Liu, the lead researcher.

From Bioinformatics to Mouse Models and Microbial Analysis

Researchers first analyzed publicly available human and mouse vascular datasets to identify LYZ upregulation associated with age or disease. They generated Lyz1 knockout mice and compared them with wild-type controls, assessing vessel health via microscopy, biochemical assays for oxidative stress, inflammatory cytokines, and senescence markers. Gut microbiota changes were measured using 16S rRNA sequencing, and vessel gene expression was analyzed by RNA sequencing to identify affected pathways. To test causality, they used antibiotic-treated and germ-free mouse models, observing similar vascular aging when microbes were depleted. Finally, they administered purified LYZ orally or intravenously to aged mice and evaluated gut bacteria and vessel markers to compare effects. This multi-angle approach combines data mining, genetic models, microbial analysis, and intervention studies to ensure rigor.

Toward Human Trials: Gut-Targeted Strategies for Vascular Well-Being

While human trials are necessary, the study points suggested that gut-targeted strategies—such as LYZ-based supplements, probiotics that enhance Bifidobacterium, or diets that support healthy microbial metabolites—help mitigate age-related vascular inflammation. This could translate into fewer cases of hypertension, atherosclerosis, and other vascular diseases in older adults, offering a non-invasive addition to existing cardiovascular care.

Published on May 2025 in Research, this collaborative effort spans Jiangnan University, Jiangsu Rongjun Hospital, Army Medical University, Jinfeng Laboratory, Affiliated Hospital of Jiangnan University, Wuxi Hospital (Nanjing University of Chinese Medicine), and Peking Union Medical College.

Sources: https://spj.science.org/doi/10.34133/research.0704