ABSTRACT
BACKGROUND AND
AIMS:
We have identified a decreased abundance of microbial species known to have a potential anti-inflammatory, protective effect in subjects that developed
Celiac Disease (CeD) compared to those
who did not. We aim to confirm the potential protective
role of one of these species, namely
Bacteroides vulgatus, and to mechanistically establish the effect of bacterial bioproducts on
gluten-dependent changes on
human gut epithelial functions.
METHODS:
We identified, isolated, cultivated, and sequenced a unique novel
strain (20220303-A2) of B. vulgatus found only in control subjects. Using a
human gut
organoid system developed from pre-celiac
patients, we monitored epithelial
phenotype and innate immune
cytokines at baseline, after exposure to
gliadin, or
gliadin plus B. vulgatus
cell free supernatant (CFS).
RESULTS:
Following
gliadin exposure, we observed increases in
epithelial cell death, epithelial monolayer
permeability, and
secretion of pro-inflammatory
cytokines. These effects were mitigated upon exposure to B. vulgatus 20220303-A2 CFS, which had matched
phenotype gene product
mutations. These protective effects were mediated by
epigenetic reprogramming of the
organoids treated with B. vulgatus CFS.
CONCLUSIONS:
We identified a unique
strain of B. vulgatus that may exert a beneficial
role by protecting CeD
epithelium against a
gluten-induced break of epithelial tolerance through
miRNA reprogramming. IMPACT Gut
dysbiosis precedes the onset of
celiac disease in genetically at-
risk infants. This
dysbiosis is characterized by the loss of protective bacterial
strains in those
children who will go on to develop
celiac disease. The
paper reports the mechanism by which one of these protective
strains, B. vulgatus, ameliorates the
gluten-induced break of gut epithelial
homeostasis by epigenetically re-
programming the target
intestinal epithelium involving pathways controlling
permeability,
immune response, and
cell turnover.
