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Increased in vitro intestinal permeability in suckling rats exposed to cow milk during lactation
T Arvola1, E Isolauri, I Rantala
1Department of Clinical Sciences, University of Tampere, Finland.
Insights
Cow milk exposure in newborn rats delays gut closure, increasing intestinal permeability to foreign antigens. This suggests cow milk antigens impair mucosal barrier function during a critical developmental period.
Area of Science:
- Immunology
- Gastroenterology
- Developmental Biology
Background:
- Newborns develop gut mucosal barrier functions to manage foreign antigens.
- Cow milk antigens may interfere with the maturation of these gut barrier functions.
Purpose of the Study:
- To investigate if cow milk antigen exposure affects the development of gut barrier function in preweaning rats.
- To assess jejunal permeability and immune activation in response to cow milk exposure during a critical developmental window.
Main Methods:
- Preweaning rats were divided into three groups: controls (maternal milk), cow milk (CM) gavage, and dam cow milk (D).
- Jejunal permeability to macromolecules (horseradish peroxidase) and immune responses were measured at 21 days.
- Specific antibody-secreting cells against beta-lactoglobulin were quantified.
Main Results:
- Intestinal absorption of intact horseradish peroxidase was significantly higher in CM and D groups compared to controls at 21 days.
- Increased jejunal permeability correlated with eosinophilic infiltration in the CM group.
- Group D showed significantly higher specific antibody-secreting cells against beta-lactoglobulin.
Conclusions:
- Exposure to cow milk antigens during a critical developmental period delays "gut closure" in rats.
- Impaired mucosal barrier function is linked to a hypersensitivity reaction to cow milk antigens.
- Maternal milk or processing does not fully protect against these effects.
Abstract:
Specific mucosal barrier functions of the gut develop in the newborn to combat the constant challenge of foreign antigens. To determine whether exposure to cow milk antigens interferes with this maturational process, jejunal permeability to macromolecules and the activation of immune mechanisms were studied in preweaning rats. At the age of 14 days, rat pups were divided into three feeding groups. Controls (n = 18) remained on normal maternal milk; group CM (n = 27) additionally received a daily gavage feed of cow milk; and in group D (n = 23), cow milk was given to dams. At 21 days, when "gut closure" normally occurs, intestinal in vitro absorption of horseradish peroxidase in its intact form was significantly higher in group CM and in group D than in controls (F = 5.6; p = 0.006): group CM: mean, 37.8 ng/h/cm2; 95% confidence interval (CI), 19.4-73.6; group D: mean, 26.9 ng/h/cm2; 95% CI, 8.2-88.2; controls: mean, 4.0 ng/h/cm2; 95% CI, 1.2-13.9. In association with increased jejunal permeability, there was enhanced jejunal eosinophilic infiltration in group CM. In group D, the number of specific antibody-secreting cells in peripheral blood against beta-lactoglobulin was significantly higher than in group CM and controls. These data indicate that there is a critical period in development when feeding cow milk antigens delays gut closure. They further suggest that mucosal barrier function is impaired due to a local hypersensitivity reaction to cow milk antigens, irrespective of the protection of maternal milk or maternal antigen processing.