Dr Paris Tavakoli, Longitudinal course of IBDs on 12 months of follow up, JGENCA July 2017

growth factor – β, and IL-35 (Vignali, Collison & Workman,
2008). IL-10 deficient mice develop spontaneous colitis
through IL-23 and TH-17 pathways. Genetically determined
deficiency of IL-10 activity could lead to severe early-onset
forms of IBD in humans.
Recently a new population of T cells known as T Helper
17 (TH-17) cells, which are responsible for production
and release of a specific proinflammatory cytokine (IL-17),
have been addressed in pathogenesis of human colitis
(Kobayashi et al., 2008). IL-23 is the cytokines that regulate
the maintenance and function of TH-17 immune cells. In
animal studies (mice), it has been shown that IL-6, TGF-β,
IL-1β, IL-23 and ATP that derives from commensal bacteria,
(such as segmented filamentous bacteria) are required for
TH-17 cells differentiation. Recent studies have directed
toward the intestinal immune modulation by the microbiota,
as it has been shown that germ-free animals have TH-17
cell development impairment and reduced level of IL-17
production in the colon (Ivanov et al., 2008) and Tregs in
these animals are not as effective as in conventionally
colonised animals (Ishikawa et al., 2008).
The human immune system plays a critical role in the
recognition, response and adaptation to countless self
and foreign molecules; so its integrity is very important in
maintaining and recovering health. The basic development
of human immune system function depends on its
interaction with the human microbiome (Macpherson &
Harris, 2004). The first line for mucosal defence is to prevent
the diffusion of foreign antigens from pathogenic bacteria
that penetrate the mucosal barrier. In all mammals, the
intestinal lumen is colonised by communities of bacteria that
result in biofilm production — the proteolytic cleavage of the
outer coating of mucus, which creates a barrier to infection.
Any challenge that alters the microbiota composition and
suppresses their regrowth can disturb the barrier, allowing
infection and disease to occur (Stecher et al., 2007). The
thickness of this mucus layer of the epithelium is correlated
to bacterial content of the intestine. It is thinner in the
proximal small intestine (containing 10 3 –10 5 organisms per
gram) and is thicker in the distal small and large intestine
(containing 10 10 –10 12 organisms per gram). Previous
studies have shown that both humans and mice normally
tolerate autologous microbiota and the breakdown of this
tolerance is associated with chronic intestinal inflammation
(Duchman et al., 1995). It is likely that potential pathological
responses to the component of intestinal flora, which are
restrained by immunoregulatory controls, do occur. When
this immune constraint is breached, it modulates the
inflammatory response (Garside, Mowat & Khoruts, 1999).
In addition, it is possible that alteration in the composition
of gut microbiota (dysbiosis), disturbs the interaction
between the immune system and microbiome and ultimately
leads to immune response alteration and may motivate
inflammatory disorders (Round & Mazmanian, 2009). IBD
patients respond to antibiotic therapy, faecal diversion and
have higher titres of antibodies against commensal bacteria,
compared to healthy individuals (Tannock, 2002). Clinically
and endoscopically, the distribution of the inflammatory
lesions of IBD is more pronounced in the areas of gut with
higher concentration of bacteria.
Conclusion
IBDs are chronic gastrointestinal inflammatory disorders.
The onset of disease is in adolescents and young adults
with the second peak in middle age (Andrews, 2014).
There are multiple genetic, environmental, psychological,
immune and microbiota factors contributing to the
manifestation and disease severity. The aetiology of IBDs
is not very well understood. Prevalence of IBD in Australia
is more than 61,000 cases diagnosed (Gastroenterology
Society of Australia, 2014). The national total hospital cost
of IBD in Australia is more than $100m per annum (PWC
Australia, March 2013). To characterise the risk factors
and vulnerabilities in remission and individual differences
and their interdependence, it is important to demonstrate
a longitudinal assessment of biological and psychological
factors and their temporal trajectory, including in relapse.
To be continued in the next GENCA Journal
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