Obesity and type 2 diabetes are associated with low-grade inflammation and specific
changes in gut micro
biota composition
1-7
. We previously demonstrat
ed that administration
of
Akkermansia muciniphila
prevents the development of obesity and associated
complications
8
. However, its mechanisms of action re
main unclear, whilst the sensitivity of
A. muciniphila
to oxygen and the presence of animal-derived compounds in its growth
medium currently limit the development of
translational approaches for human medicine
9
.
Here we addressed these issues by showing that
A. muciniphila
retains its efficacy when
grown on a synthetic medium compatible wi
th human administration. Unexpectedly, we
discovered that pasteurization of
A. muciniphila
enhanced its capacity to reduce fat mass
development, insulin resistance and dyslip
idemia in mice. These improvements were
notably associated with a modulation of
the host urinary meta
bolomics profile and
intestinal energy absorption.
We demonstrated that Amuc_1100,
a specific prot
ein isolated
from the outer membrane of
A. muciniphila
, interacts with Toll-Like
Receptor 2, is stable at
temperatures used for pasteurization, improves
the gut barrier and partly recapitulates the
beneficial effects of the bacterium. Finally,
we showed that administration of live or
pasteurized
A. muciniphila
grown on the synthetic medium is
safe in humansThese findings
provide support for the use of
different preparations of
A. muciniphila
as therapeutic
options to target human obesity and associated disorders.