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physical exercise, stress) or, even more importantly, by
environmental factors such as diet (high in sugars, low
in fibre), xenobiotics (antibiotics and other medication,
food additives, chlorine in water), or hygienic surroundings. Interestingly, in addition to diet, caging factors including ventilation and bedding type are the
most significant gut microbiota-altering environmental
factors in laboratory mice.5
Dysbiotic microbiota can influence the host's
immune system and mucosal integrity through a variety
of mechanisms. These include the modulation of
inflammasome signalling through microbial metabolites, the modulation of Toll-like receptor (TLR) and
NOD-like receptor (NLR) signalling, the degradation
of secretory IgA (sIgA), shifting in the balance between
regulatory and pro-inflammatory T cell subsets, direct
mucolytic activity and others.6 Whether dysbiosis is the
direct cause of a disease or a consequence of diseaserelated changes in the host's physiology remains
unclear. However, there are several examples, including
the type 1 diabetes (T1D), coeliac disease and
Parkinson's disease, where alterations in gut microbiota
precede the onset of illness.7-9 Also, microbiota transplantation from patients or diseased mice to germ-free
or antibiotic-treated mice shows that it is possible to
transfer a disease phenotype. This suggests a causative
role of gut microbiota in disease pathogenesis.10,11
Significantly, a disease severity rate of more than
70% in relation to gut microbiota composition has
been shown by correlation studies for some diseases,
including the type 2 diabetes and atopic dermatitis.12
In this review, we discuss essential epidemiological
data, known pathogenetic factors including those of
genetic and environmental nature; focusing mainly on
the role of gut microbiota in the development of
selected gastrointestinal and liver diseases. Using specific examples, we also briefly describe some of the most
widely-used animal models including gnotobiotic mice
and their contribution to the research of pathogenetic
mechanisms of the host-microbiota relationship.

Microbiota and inflammatory bowel
disease
Inflammatory bowel disease (IBD) is a group of multifactorial disorders characterised by chronic relapsing
inflammation of the intestinal wall and extra-intestinal
organs.6 IBD consists of two major types, Crohn's disease (CD) and ulcerative colitis (UC). CD can affect
any part of the gastrointestinal tract from mouth to
anus, yet most commonly occurs in the terminal
ileum. UC usually affects only the rectum and colon
causing continuous lesions of the mucosa and superficial submucosa, whereas CD is characterised by transmural 'skip lesions' of the intestinal wall. The most

Laboratory Animals 53(3)
commonly affected extraintestinal sites are the joints,
skin and eyes.13 The typical symptoms of active IBD
are diarrhoea, fever and fatigue, abdominal pain, blood
in the stool, poor appetite and weight loss. The incidence of IBD is stabilising in North America and
Europe, but its prevalence continues to rise and exceeds
0.3%. However, since 1990, the IBD incidence has been
rising in newly industrialised countries with westernised
societies in Africa, Asia and South America.14
The pathogenesis of IBD is not yet fully known, but
it is widely accepted that chronic inflammation in IBD
is driven by dysregulated immune response to either gut
microbiome components including bacteria, fungi,
viruses, or protozoa or dietary antigens in a genetically
susceptible host. Genome-wide association studies
(GWAS) have revealed 240 single nucleotide polymorphisms (SNPs) that are associated with IBD.15
Many of the genes, such as Nod2, TLR4, ATG16L1,
IRGM, IL-10R, or IL-23R play an essential role in
microbial sensing, autophagy, or immune response
and may affect gut microbiota composition.16
However, genetic factors, having remained relatively
stable for hundreds of years, cannot explain the
increase in incidence. So, changing lifestyle and environmental factors including a lack of physical activity,
stress, dietary changes, chlorine in water, xenobiotics
such as food additives and medication are most likely
the main culprits.6,17,18
Not surprisingly, IBD is associated with compositional and functional alterations of gut microbiota.
The most consistent finding in patients with IBD is
reduced microbiota diversity represented mainly by a
decrease in the relative abundance of Firmicutes
phylum and an increase in Proteobacteria phylum.4,19
Changes in the abundance of Bacteroidetes phylum are
less consistent with some studies reporting a
decrease,4,19 but others reporting an increase in relative
abundance.20-22 At the species level, there is a decrease
in short-chain fatty acids (SCFA) producing bacteria,
such as Faecalibacterium prausnitzii and the Clostridium
clusters IV, XIVa and XVIII,23,24 an increase in sulphate-reducing
bacteria
(SRB)
such
as
Desulfovibrio,25,26 an increase in mucolytic bacteria
for instance Ruminococcus gnavus and Ruminococcus
torques,27 and in addition, a disbalance of inflammatory
and anti-inflammatory species.4,28 Interestingly, some
studies report the increased abundance of human enteropathogens such as pathogenic Escherichia coli,
Clostridium difficile, Fusobacterium nucleatum and/or
Campylobacter species.20,29,30 However, the causal relationship, for a single bacterium, has not yet been
proved.
Due to high interindividual variations of faecal
microbiome profiles of both CD and UC patients, it
is difficult to discriminate between these diseases on



Laboratory Animals - June Issue

Table of Contents for the Digital Edition of Laboratory Animals - June Issue

Contents
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