Butyrate alleviates food allergy by improving intestinal barrier integrity through suppressing oxidative stress-mediated Notch signaling.
Level 4 - case-series / case-control
Human case-control study paired with mechanistic animal and in vitro models
PubMed 40469511 · doi:10.1002/imt2.70024
What was done
Researchers measured fecal short-chain fatty acid (SCFA) profiles across three pediatric groups: food-sensitized tolerance (n = 20), food allergy (n = 20), and healthy controls (n = 20). An ovalbumin-sensitized mouse model was used to evaluate how SCFAs affect allergic reactions, gut microbiota, tight junction integrity, mucosal barrier function, oxidative stress, and Notch signaling. Rat small intestine crypt epithelial cells (IEC-6) were exposed in vitro to low (0.25-1 mM) and high (2-5 mM) concentrations of butyrate to assess cellular oxidative injury and Notch activation.
What was found
Healthy controls had higher fecal SCFA levels than the food-sensitized tolerance, food allergy, and combined groups (exact numerical concentrations were not reported in the abstract). In the mouse model, butyrate reduced allergic responses more effectively than other SCFAs, restored microbiota balance, and blocked ovalbumin-induced reactive oxygen species and excessive Notch signaling that compromised tight junctions. In vitro, low-dose butyrate (0.25-1 mM) inhibited reactive oxygen species and protected epithelial cells, whereas high-dose butyrate (2-5 mM) worsened oxidative injury and activated Notch signaling.
Why it matters
The findings identify a potential mechanism by which microbial butyrate supports gut barrier integrity in food allergy via Notch signaling regulation, while demonstrating a biphasic dose effect where higher concentrations exacerbate epithelial oxidative stress.
Limits
The human component was restricted to a small cross-sectional case-control comparison (60 children total) without longitudinal tracking, dietary controls, or reported quantitative SCFA values in the abstract. Causality and the dual-dose therapeutic effects were demonstrated solely in rodent and cell-line models, which may not directly reflect human intestinal physiology.
Cited by
- supports The gut microbiome functions to support and maintain the integrity of the intestinal epithelial barrier (gut lining).