# Immunization With Bovine Milk Casein Results in Enteric Nervous System Pathology in a Mouse Model of Neuroinflammation

## TL;DR

Immunizing mice with bovine milk casein causes damage to their gut nervous system, possibly through immune reactions similar to those in multiple sclerosis.

## Contribution

This study shows that bovine milk casein can induce enteric nervous system pathology through both cellular and humoral immune mechanisms.

## Key findings

- Immunization with bovine milk casein leads to ENS pathology in mice.
- Both T cell infiltration and antibody binding contribute to ENS damage.
- Casein-induced pathology may involve molecular mimicry and antibody cross-reactivity.

## Abstract

Multiple sclerosis (MS) is an immune‐mediated demyelinating disease of the central nervous system (CNS) with evidence of autoimmune attack also on the enteric nervous system (ENS). The role of different dietary antigens, including bovine milk proteins, in the exacerbation of MS symptoms has previously been discussed.

In a mouse model of neuroinflammation, we characterized the extent of ENS pathology in animals that were immunized with different bovine milk antigens using electron microscopy, immunohistochemistry, molecular biology, and cell culture as key methods.

Our data demonstrate that immunization of mice with bovine milk casein resulted in ENS pathology, which is in line with our previous findings where casein‐immunized mice also exhibited demyelination in the CNS. Furthermore, development of ENS pathology was most likely due to a combination of cellular and humoral factors, as confirmed by our observation of CD3+ T cell infiltration in the tunica muscularis and binding of serum antibodies from casein‐immunized mice to glial cells in the myenteric plexus.

The findings presented in this paper reflect that exposure to bovine casein can result in axolysis in the myenteric plexus possibly as a result of molecular mimicry and antibody cross‐reactivity between casein and antigen(s) expressed by the ENS.

Experimental study design. Mice were immunized with either α‐Lactalbumin or casein, and the resulting pathology of the enteric nervous system (ENS) was assessed using electron microscopy and immunofluorescence imaging. In vitro culture of isolated cells of the ENS was used to complement the in vivo findings.