Ovotransferrin Alleviates Ulcerative Colitis by Modulating Ligilactobacillus murinus-Mediated Bile Acid Metabolism via the Ptgs2/JAK-STAT Signaling Axis.
Zheng D, Xin X, et al. • Journal of agricultural and food chemistry • 2026
Ovotransferrin alleviates ulcerative colitis via an 'OVT-L. murinus-bile acids-Ptgs2/JAK-STAT' axis, wherein OVT reshapes gut microbiota to enrich Ligilactobacillus murinus, which drives secondary bile acid biosynthesis through bile salt hydrolase activity, ultimately suppressing inflammation via Ptgs2 (COX-2) downregulation and JAK-STAT signaling pathway inhibition.
Key Findings
Results
Ovotransferrin alleviates DSS-induced ulcerative colitis and reshapes gut microbiota composition in a mouse model.
A dextran sulfate sodium (DSS)-induced UC mouse model was used to investigate OVT's effects.
OVT treatment was associated with changes in gut microbiota composition in colitis mice.
OVT is described as a 'functionally active protein demonstrated to alleviate ulcerative colitis' with previously incompletely understood mechanisms.
The study established a mechanistic axis linking OVT to microbial and metabolic changes.
Results
Ligilactobacillus murinus was isolated from the gut microbiota of OVT-treated UC mice and was directly stimulated by OVT in vitro.
L. murinus was specifically isolated from gut microbiota of OVT-treated colitis mice, implicating it as a key mediator of OVT's effects.
OVT was shown to stimulate L. murinus growth or activity in vitro, suggesting a direct prebiotic-like relationship.
L. murinus enrichment was identified as a specific microbiota change associated with OVT treatment.
Results
Whole-genome sequencing revealed that L. murinus encodes bile salt hydrolase, enabling it to drive secondary bile acid biosynthesis.
Integrated whole-genome sequencing was combined with targeted metabolomics to characterize L. murinus metabolic capacity.
The genome of L. murinus was found to encode bile salt hydrolase (BSH), a key enzyme in bile acid metabolism.
BSH activity by L. murinus drives secondary bile acid biosynthesis, linking microbiota changes to specific metabolic outputs.
Targeted metabolomics confirmed the production of secondary bile acids associated with L. murinus activity.
Results
Fermentation products derived from co-culture of L. murinus with bile exerted potent anti-inflammatory effects in Caco-2 cells.
Fermentation products (FP) were generated by co-culturing L. murinus with bile in vitro.
These FP demonstrated anti-inflammatory activity in Caco-2 intestinal epithelial cells.
The anti-inflammatory mechanism involved downregulation of Ptgs2 (COX-2) expression.
JAK-STAT signaling pathway inhibition was identified as part of the anti-inflammatory mechanism in Caco-2 cells.
Results
Fermentation products from L. murinus-bile co-culture also demonstrated anti-colitis effects in a mouse colitis model through Ptgs2 downregulation and JAK-STAT pathway inhibition.
In vivo validation was performed in a colitis mouse model using L. murinus-derived fermentation products.
Ptgs2 (COX-2), a key pro-inflammatory enzyme, was downregulated following treatment with fermentation products.
The JAK-STAT signaling pathway was inhibited by FP treatment in the colitis model.
Both in vitro (Caco-2) and in vivo (colitis model) systems confirmed consistent anti-inflammatory mechanisms.
Conclusions
The study established a novel 'OVT-L. murinus-bile acids-Ptgs2/JAK-STAT' mechanistic axis for UC treatment.
The mechanistic axis links dietary protein OVT to gut microbiota modulation, bile acid metabolism, and inflammatory signaling.
This axis represents a previously uncharacterized mechanism of OVT action in ulcerative colitis.
The findings are proposed to provide 'a foundation for high-value applications of OVT in functional foods.'
The study integrates microbiomics, genomics, metabolomics, and cell/animal models to support the proposed axis.
What This Means
This research suggests that ovotransferrin (OVT), a protein found in egg whites, can help reduce the severity of ulcerative colitis (UC) — a chronic inflammatory bowel disease — by changing the balance of bacteria living in the gut. Using a mouse model of colitis, researchers found that OVT treatment increased the abundance of a specific beneficial bacterium called Ligilactobacillus murinus. This bacterium carries a gene that allows it to chemically modify bile acids (digestive compounds made by the liver), converting them into secondary bile acids that have anti-inflammatory properties. When researchers grew L. murinus together with bile in the laboratory, the resulting fermentation products reduced inflammation both in intestinal cells and in colitis mice, by turning down two key inflammatory pathways: one involving an enzyme called COX-2 (encoded by the Ptgs2 gene) and another called the JAK-STAT signaling pathway.
This research suggests a clear chain of events — OVT promotes growth of L. murinus, which transforms bile acids into anti-inflammatory compounds, which then suppress specific inflammatory signals in the gut — providing a detailed mechanistic explanation for why OVT reduces colitis symptoms. This is significant because while OVT was already known to have some anti-inflammatory effects, the specific biological pathway had not previously been mapped out. The discovery that OVT works partly by reshaping the gut microbiome and influencing bile acid chemistry opens a new understanding of how dietary proteins can interact with gut bacteria to influence disease.
From a practical standpoint, this research suggests that OVT — being a naturally occurring egg white protein — could potentially be used as a functional food ingredient to support gut health, particularly in people with inflammatory bowel conditions. The identification of L. murinus as a key mediator also raises the possibility of probiotic approaches targeting this bacterium. However, these findings are currently based on mouse models and cell culture experiments, and further research in humans would be needed before any clinical applications could be considered.
Zheng D, Xin X, Ouyang H, Ma L, Wang H, Liu X, et al.. (2026). Ovotransferrin Alleviates Ulcerative Colitis by Modulating Ligilactobacillus murinus-Mediated Bile Acid Metabolism via the Ptgs2/JAK-STAT Signaling Axis.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c01625