Theabrownin enhances intestinal barrier integrity and microbiota balance through modulation of the ST6GalNAc6-STn-MUC2 axis in DSS-induced colitis mice, highlighting its potential as a functional food ingredient for gut health management.
Key Findings
Results
Theabrownin (TB) administration markedly alleviated body weight loss and colon injury in DSS-induced colitis mice.
TB was administered at a dose of 1 g per kg body weight
The colitis model was induced using dextran sulfate sodium salt (DSS)
TB treatment led to marked alleviation in body weight loss compared to untreated colitis mice
Colon injury was visibly reduced in TB-treated animals
Results
TB significantly enhanced goblet cell function and mucus layer integrity in DSS-induced colitis mice.
TB treatment supported goblet cell function, which is critical for mucus production
Mucus layer integrity was restored, contributing to epithelial defense
These effects were associated with downstream microbial homeostasis improvements
Goblet cell and mucus layer improvements were mechanistically linked to the ST6GalNAc6-STn-MUC2 axis
Results
TB restored microbial balance by enriching Prevotellaceae_UCG-001 while suppressing Eubacterium and Parasutterella.
Microbial composition was assessed using 16S rDNA sequencing
TB treatment specifically enriched the taxon Prevotellaceae_UCG-001
TB suppressed the abundance of Eubacterium and Parasutterella
These microbiota changes are consistent with restoration of microbial homeostasis in colitis
Results
TB upregulated ST6GalNAc6, reduced sialyl-Tn (STn) expression, and normalized MUC2 sialylation as its mechanistic pathway.
ST6GalNAc6 is a sialyltransferase involved in glycan modification of mucins
TB treatment increased ST6GalNAc6 expression in colitis mice
Sialyl-Tn (STn) expression was reduced following TB treatment, indicating normalized glycosylation
MUC2 sialylation was normalized, which is critical for proper mucin function and barrier integrity
Results
Inhibition of ST6GalNAc6 with 3Fax-Neu5Ac abrogated the protective effects of TB, confirming the ST6GalNAc6-STn-MUC2 axis as the mechanistic pathway.
3Fax-Neu5Ac is a sialyltransferase inhibitor used to block ST6GalNAc6 activity
Inhibition of ST6GalNAc6 with 3Fax-Neu5Ac abolished TB's protective effects on intestinal barrier integrity
This pharmacological inhibition experiment confirmed the causal role of the ST6GalNAc6-STn-MUC2 axis
The abrogation of protective effects validates that TB acts specifically through modulation of MUC2 sialylation
Background
Theabrownin, a major bioactive compound from Pu-erh tea, demonstrated previously unclear mechanisms of intestinal barrier protection beyond known anti-inflammatory properties.
TB is described as 'a major bioactive compound derived from Pu-erh tea'
Prior literature had established TB's anti-inflammatory properties
The specific role of TB in intestinal barrier protection and its underlying mechanisms were previously unclear
This study identifies the ST6GalNAc6-STn-MUC2 axis as a novel mechanistic target
What This Means
This research suggests that theabrownin (TB), a bioactive compound found in Pu-erh tea, can help protect the gut lining and restore a healthy balance of gut bacteria in mice with induced colitis (a model of inflammatory bowel disease). When mice with colitis were given TB at a dose of 1 gram per kilogram of body weight, they experienced less weight loss, less colon damage, and improved function of the mucus-producing goblet cells that line the intestine. The researchers also found that TB helped restore a healthier community of gut microbes, increasing beneficial bacteria like Prevotellaceae_UCG-001 while reducing potentially harmful ones.
The study identified a specific molecular mechanism behind these benefits: TB activates an enzyme called ST6GalNAc6, which in turn controls how a key mucus protein (MUC2) is chemically modified. In colitis, this modification process goes awry, leading to abnormal mucus and a weakened gut barrier. TB corrected this process, and when the researchers blocked ST6GalNAc6 with a chemical inhibitor, TB's protective effects disappeared, confirming this pathway is essential to how TB works.
This research suggests that theabrownin from Pu-erh tea could have potential as a functional food ingredient for supporting gut health, particularly by strengthening the intestinal mucus barrier and promoting a balanced microbiome. The findings provide a specific biological explanation for how a dietary compound found in fermented tea may help manage intestinal inflammation, which could be relevant to conditions like ulcerative colitis.
Xie K, Qin Y, Li L, Zhu Q, Ye T, Wang W, et al.. (2026). Theabrownin derived from Pu-erh tea enhances intestinal barrier integrity and microbiota balance via the ST6GalNAc6-STn-MUC2 axis in inflammation.. Food & function. https://doi.org/10.1039/d5fo05118e