Gut Akkermansia muciniphila ameliorates non-alcoholic fatty liver
disease by L-aspartate via interaction with liver
Abstract
Background and Purpose The human gut bacterium Akkermansia muciniphila
has been increasingly recognized for its therapeutic potential in
treating metabolic disorders. However, its efficacy in preventing
non-alcoholic fatty liver disease (NAFLD) and the mechanism involved in
its well-known metabolic actions are unknown. The present study explored
the therapeutic effect and novel mechanism of A. muciniphila in
intervening NAFLD. Experimental Approach The anti-NAFLD activity of A.
muciniphila was evaluated in an obese mouse model induced by high-fat
and cholesterol (HFC) diets using three different interventions. The gut
microbiota composition, beneficial metabolic effects in the gut-liver
axis were explored. The level and beneficial metabolic effects of
L-aspartate in vitro and in vivo were further determined. Key Results
Mice treated with A. muciniphila efficiently reversed NAFLD in the
liver, such as hepatic steatosis, inflammatory, and liver injury. These
therapeutic effects persisted after long-term drug withdrawal and were
slightly weakened in a germ-free mouse model. A. muciniphila treatment
efficiently increased mitochondrial oxidation and bile acid metabolism
in the gut-liver axis, ameliorated oxidative stress- induced cell
apoptosis in the gut, leading to the reshaping of the gut microbiota
composition. These metabolic improvements occurred with increased
L-aspartate levels in the liver that transported from the gut. The
administration of L-aspartate in vitro or in mice displayed the similar
beneficial metabolic effects mentioned above. Conclusion and
Implications The anti-NAFLD activity of A. muciniphila correlated with
lipid oxidation and improved gut-liver interactions through regulating
L-aspartate metabolism. A. muciniphila would be a potent agent for
clinical intervention in NAFLD.