- A typical western
diet is high in fat and sugar and causes inflammation of liver cells.
- The diet changes
the gut microbiota and the bile acid profile.
- Probiotics can be
used to prevent and treat hepatic inflammation and progression of advanced
liver diseases such as cancer.
western diet pattern, or the otherwise called
meat-sweet diet is composed of red meat, processed meat, butter, high-fat
dairy, refined grains, high sugar and is about 50% carbohydrates, 15% protein
and 35% fat.
The Western pattern diet, based on epidemiological studies of Westerners, is
positively correlated with an elevated incidence of obesity, death from heart disease, cancer when compared to a healthy diet.
‘Probiotics and bile acid receptor agonists may be useful for the prevention and treatment of hepatic inflammation and progression into advanced liver disease.’
study has been done in mice which reports that feeding a Western diet
which is high in fat and sugar, resulted in hepatic inflammation, especially in
know the transition from steatosis, or fatty liver, to steatohepatitis
(inflammation in the fatty liver) plays a crucial role in liver injury and
carcinogenesis. Because the liver receives 70% of its blood supply from the
intestine, it is important to understand how the gut contributes to liver
disease development," explained lead investigator Yu-Jui Yvonne Wan, PhD,
Professor and Vice Chair of the Department of Pathology and Laboratory Medicine
at UC Davis Health.
Western Diet Pattern
Induces Liver Inflammation
and her team used mice that lacked farnesoid x receptor (FXR), a bile acid
receptor. The FXR-deficient mouse model an important tool to better understand
the role of diet and inflammation in the development of liver diseases as patients
with cirrhosis or liver cancer also have low FXR levels.
done studies have shown that FXR-deficient mice spontaneously develop
steatohepatitis and liver tumors even when they are fed a normal rodent diet.
study, wild-type and FXR-deficient mice were either fed with a control diet or
a western diet for 10 months. Both Western diet-fed mice and control diet-fed
FXR KO mice developed steatosis or abnormal retention of lipids within the
cells. Steatosis was more severe in males than females.
FXR-deficient male mice had massive lymphocyte and neutrophil infiltration in
the liver, which means that white blood cells have left the blood stream and
migrated into a tumor.
the western diet-fed male FXR KO mice had fatty adenomas which are uncommon benign liver
tumors that are hormone
studies show that a Western diet intake and FXR inactivation also increased
hepatic inflammatory signaling, with a combined enhanced effect," Dr. Wan
Response To Antibiotics
combination of ampicillin
, and vancomycin were
introduced to reduce inflammation. Based on the diets the mice received, the
effect of antibiotics was varied.
control-diet fed mice, the antibiotics completely blocked hepatic neutrophil
and lymphocyte infiltration.
FXR-deficient mice had more hepatic inflammation as the antibiotics altered the
inflammatory genes had higher expression levels in Western diet than control
diet-fed FXR KO mice after antibiotic treatment. Liver cells synthesize gut
bacteria and bile acids which help in lipid and sugar homeostasis as well as
said, "Gut and liver health are linked. It is clear that microbial
imbalance and dysregulated bile acid synthesis are inseparable, and they
jointly contribute to hepatic inflammation via the gut-liver axis."
reduced hepatic inflammation by antibiotics was accompanied by decreased free
and conjugated secondary bile acids in a gender-dependent manner.
Altered Gut Bacteria
analyzing the gut bacteria
composition, investigators found that
Proteobacteria and Bacteroidetes persisted after the broad-spectrum antibiotic
treatment in the Western diet-fed FXR KO mice.
antibiotic polymyxin B, increased Firmicutes and decreased Proteobacteria, as well as, hepatic inflammation in Western
diet-fed FXR KO male mice.
microbiota and bile acid profiles may explain gender difference in liver
disease as liver cancer incidence is much higher in men than women" noted Dr.
adverse effects of the Western diet might be due to the persistence of
Proteobacteria which causes inflammation and the reduced levels of
anti-inflammatory Firmicutes in the gut.
the treatment of antibiotics, gut bacteria which produce bile acid can directly
be eliminated which also causes changes in the bile acid composition. The study
sheds light on the effect of a high fat high sugar diet which destroys liver
cells. Also, the treatment of antibiotics to reduce the inflammation in the
liver cells acts in a gender-based manner and destroys bacteria which help in
bile acid production.
Probiotics Can Be Useful
in Liver Disease
a healthy gut is crucial for the treatment of liver steatosis. The use of
antibiotics to eliminate infection can ultimately destroy bacteria which helps
synthesize bile acids. So, introducing probiotics can
help maintain a varied population of gut bacteria that may help reduce liver inflammation
results suggest that probiotics and FXR agonists hold promise for the
prevention and treatment of hepatic inflammation and progression into advanced
liver diseases such as cancer," claims Dr. Wan.
- Yu-Jui Yvonne Wan et al., Western Diet-Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment, The American Journal Of Pathology, http://dx.doi.org/10.1016/j.ajpath.2017.04.019.