Oral lysozyme attenuates TBI-induced neuroinflammation and brain injury potentially through gut microbiota-dependent tryptophan metabolism reprogramming, with concordance between preclinical and clinical metabolomic data supporting lysozyme as a candidate microbiota-targeted therapeutic strategy.
Oral lysozyme improved neurological outcomes and attenuated neuronal apoptosis and neuroinflammation in a severe TBI mouse model.
Oral lysozyme restored peripheral CD4+/CD8+ T cell homeostasis following TBI.
Fecal untargeted metabolomics revealed enrichment of tryptophan metabolites—indole-3-carboxaldehyde, indolelactic acid, and kynurenic acid (KYNA)—following oral lysozyme treatment.
The metabolic effects of oral lysozyme were abolished by antibiotic-mediated microbiota depletion and reproduced by fecal microbiota transplantation (FMT), confirming gut microbiota dependence.
In human patients with severe TBI, favorable clinical outcomes were associated with higher CSF kynurenic acid (KYNA) levels and an elevated KYNA/quinolinic acid (QA) ratio.
The KYNA/QA ratio was identified as a candidate prognostic indicator in severe TBI, warranting further validation in larger, longitudinal cohorts.
Preclinical and clinical metabolomic data showed concordance in tryptophan metabolite patterns, supporting translational relevance of the mouse model findings.
Oral lysozyme was associated with restoration of intestinal barrier integrity following TBI-induced gut dysbiosis.
This research suggests that taking lysozyme by mouth—an enzyme naturally found in saliva and tears—may help protect the brain after a traumatic brain injury (TBI) by changing how gut bacteria process a dietary amino acid called tryptophan. In mice with severe TBI, oral lysozyme improved neurological recovery, reduced brain inflammation, decreased nerve cell death, and helped restore normal immune cell balance in the blood. Importantly, these benefits disappeared when the gut bacteria were wiped out with antibiotics and returned when gut bacteria from treated mice were transplanted into other animals, confirming that the gut microbiome is essential to lysozyme's effects. The key mechanism appears to involve shifting tryptophan breakdown in the gut and brain toward producing more kynurenic acid (KYNA), a molecule with neuroprotective properties, rather than quinolinic acid (QA), which can be harmful to the brain. To test whether these findings might apply to humans, the researchers analyzed cerebrospinal fluid (the fluid surrounding the brain and spinal cord) from 10 matched pairs of patients with severe TBI. They found that patients who had better clinical outcomes had higher levels of KYNA and a higher KYNA-to-QA ratio in their spinal fluid, mirroring what was seen in the mouse experiments. This agreement between the animal and human data strengthens the case that this metabolic pathway is genuinely relevant to brain injury recovery in people. This research suggests that oral lysozyme could be a practical, microbiome-targeted treatment strategy for TBI, since it is already a widely used and generally safe compound. It also suggests that the ratio of KYNA to QA in spinal fluid might serve as a useful marker to predict outcomes in TBI patients, though the human study was small (only 10 matched pairs) and the authors emphasize that larger, longer-term studies are needed before any clinical conclusions can be drawn.
Du Z, Yao H, Xi C, Yuan Q, Fu P, Hu J, et al.. (2026). Oral Lysozyme Attenuates Neuroinflammation and Brain Injury After Traumatic Brain Injury Through Gut Microbiota-Dependent Reprogramming of Tryptophan Metabolism.. CNS neuroscience & therapeutics. https://doi.org/10.1002/cns.71025