Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice

Ulcerative colitis (UC) is characterized by
chronic inflammation of the colonic mucosa. Administration
of dextran sulfate sodium (DSS) to animals is a frequently
used model to mimic human colitis. Deregulation
of the immune response to the enteric microflora or
pathogens as well as increased intestinal permeability have
been proposed as disease-driving mechanisms. To enlarge
the understanding of the pathogenesis, we have studied the
effect of DSS on the immune system and gut microbiota in
mice. Intestinal inflammation was verified through histological
evaluation and myeloperoxidase activity. Immunological
changes were assessed by flow cytometry in
spleen, Peyer0s patches and mesenteric lymph nodes and
through multiplex cytokine profiling. In addition, quantification
of the total amount of bacteria on colonic mucosa
as well as the total amount of lactobacilli, Akkermansia,
Desulfovibrio and Enterobacteriaceae was performed by
the use of quantitative PCR. Diversity and community
structure were analysed by terminal restriction fragment
length polymorphism (T-RFLP) patterns, and principal
component analysis was utilized on immunological and
T-RFLP patterns. DSS-induced colitis show clinical and
histological similarities to UC. The composition of the
colonic microflora was profoundly changed and correlated
with several alterations of the immune system. The results
demonstrate a relationship between multiple immunological
changes and alterations of the gut microbiota after DSS
administration. These data highlight and improve the definition
of the immunological basis of the disease and
suggest a role for dysregulation of the gut microbiota in the
pathogenesis of colitis.