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Hrncir et al.
This signiﬁcant ﬁnding suggests that the presence of
dysbiosis in coeliac patients could modulate autoimmune risks in genetically susceptible individuals.85
An interesting and important study performed on
mice was published very recently demonstrating that
reovirus, a common and otherwise harmless virus present in the gut during the postnatal period, can trigger a
damaging immune response to gluten and contribute to
the development of coeliac disease.86
Despite the fact that animal models of human diseases have their limitations, they help us to understand
the complex mechanisms occurring during host-
microbe interactions and enable us to analyse the eﬀects
of microbiota on immune reactivity to food components (especially gluten).84

Microbiota and non-alcoholic fatty liver
disease
Compositional and functional alterations of gut microbiota are also associated with the development and
progression of a number of liver diseases including
non-alcoholic fatty liver disease (NAFLD), alcoholic
liver disease (ALD), cirrhosis, or hepatocellular carcinoma.87 NAFLD, the hepatic manifestation of insulin
resistance and metabolic syndrome, is characterised
by hepatic triglyceride accumulation without signiﬁcant
alcohol consumption.88 The global prevalence of
NAFLD has been rapidly increasing and is currently
estimated at 24%.89 An inﬂammatory form of
NAFLD, non-alcoholic steatohepatitis (NASH), can
potentially progress to advanced liver disease, cirrhosis
and hepatocellular carcinoma.90 The factors contributing to the progression of NAFLD towards NASH
remain incompletely understood.
Gut microbiota is an important factor involved in
NAFLD pathogenesis. There is a direct anatomical
link, the portal vein, between the gut and liver. Thus,
gut microbiota and its metabolites could easily inﬂuence liver physiology. When the gut barrier, made of
a single layer of epithelial cells sealed with tight-junction proteins, is compromised then the impact of gut
microbiota and food-derived molecules on the liver will
be even more pronounced. Cani et al. showed that dietary fat and glucose could lead to gut barrier injury and
increased gut permeability to bacteria, its components
and metabolites.91 Therefore, pro-inﬂammatory bacteria-derived molecules, such as lipopolysaccharide
(LPS), can induce liver injury by the activation of
Kupﬀer cells via TLR4 signalling.92 Several human93
and animal94-96 studies suggest that a high intake of
carbohydrates, particularly fructose, is closely linked
to the development of NAFLD. NASH patients, as
well as obese patients, have dysbiosis characterised, at
the phylum level, by an increase in Bacteroidetes and

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Proteobacteria and a decrease in Firmicutes.97 Also,
fructose-induced NAFLD is associated with alterations
in gut microbiota composition as well as increased gut
permeability resulting in endotoxin translocation, activation of Kupﬀer cells via TLR4 and M1 macrophages
which leads to chronic hepatic inﬂammation and
injury.96 Interestingly, probiotics in animal studies
were shown to correct dysbiosis by inhibiting proliferation of harmful bacteria and to improve gut barrier
function by upregulating the expression of tight junction proteins.98

Microbiota and ALD
ALD, which is caused by chronic excess alcohol consumption, is a major cause of liver-related morbidity
and mortality. Like NAFLD, early stage ALD, represented by asymptomatic and reversible steatosis, may
progress to steatohepatitis, ﬁbrosis, cirrhosis and its
complications (such as portal hypertension, ascites,
variceal bleeding or hepatic encephalopathy), or even
hepatocellular carcinoma. The ALD pathogenetic
mechanisms are not entirely understood, but recent
research indicates that gut microbiota including its
fungal component may play an essential role. ALD is
associated with gut dysbiosis and increased permeability resulting in increased translocation of microbial and
fungal products from the gut, via the portal vein, into
the liver. ALD patients, as well as NAFLD patients,
often demonstrate small intestinal bacterial overgrowth
(SIBO).99,100 ALD-associated dysbiosis is characterised
by an increase in Enterobacteriaceae and a decrease in
Bacteroidetes, Lactobacillus and A. muciniphila.101-105
Interestingly, the susceptibility to alcohol-induced
liver injury is transmissible from alcoholic hepatitis
(AH) patients to both germ-free and conventional
mice by FMT and, conversely, the gut microbiota
transferred from alcoholic patients without AH shows
a protective eﬀect.106 Also, in a diﬀerent study, alcohol
sensitivity was shown to be dependent on gut microbiota, because FMT from alcohol-resistant to alcoholsensitive mice prevented steatosis, liver inﬂammation
and restored gut homeostasis.107 Recent research
shows that supplementation of depleted commensals
might be beneﬁcial in ALD treatment.105 For example,
A. muciniphila, a Gram-negative intestinal commensal,
is heavily depleted in both ALD patients and ethanolfed mice and its abundance indirectly correlates with
disease severity. The A. muciniphila supplementation
promotes intestinal barrier integrity and ameliorates
liver injury in ethanol-fed mice.105
Interestingly, recent work by Yang et al.108 shows
that intestinal fungi also contribute to ALD development. In this study, ALD patients demonstrated
decreased fungal diversity and richness and signiﬁcant
Laboratory Animals - June Issue

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