tium, which irst colonises the caecum before infecting the rest
of the gastrointestinal tract. This infection strongly resembles
infections that cause severe cases of diarrhoea in people.
Gut Specialisation
Although the gut is essentially a single continuous tube, it is
divided into specialised segments that are involved in different
parts of the digestion process. For example, 90% of digestion and
absorption of nutrients takes place in the human small intes-
tine with the remaining 10% taking place in the stomach and
large intestine.
The caecum is a small pouch at the beginning of the large
intestine that intriguingly contains a large patch of immune
cells near its tip. In large animals such as cows, horses and even
koalas, the caecum is home to bacteria that digest the tough
plant components in the diet.
In humans, however, this part of the gut is much reduced in
size and the part that contains the immune cell patch is found
in what is now a smaller appendage to the caecum, the appendix.
This immune cell patch is important for initiating immune
responses and is sometimes a target for the colonisation of
various pathogenic microbes.
The appendix is not required for digestive functions in
humans but normally houses symbiotic bacteria that are impor-
tant for overall gut health. Randall Bollinger and Bill Parker
at Duke University have suggested that these symbiotic bacteria
play a more prominent role following gut infections that can
result in diarrhoea. Such an infection effectively cleans out the
gut, not only of luids and nutrients but also of good bacteria.
Bollinger and Parker proposed that the good bacteria harboured
in the appendix provide a site where the body’s own microbial
culture is sequestered so that it can repopulate the gut after the
infection is over.
Our group was able to create mice in which we manipulated
or deleted the innate lymphoid cells and/or the adaptive immune
cells to test how each of these populations are involved in the
development of intestinal disease following C. rodentiuminfec-
tion. The worst outcome occurred when both innate and adap-
tive cell subsets were depleted. To our surprise, the caecum was
quite shrunken and clearly not performing its usual function
of processing food as it moves towards the colon.
We found that altering the balance of the different types of
immune cells signiicantly affected what was happening in the
caecum. It made us wonder if a similar effect might occur in
humans in the appendix. Could it be that this organ, which is often
considered irrelevant, may indeed play a very important role?
We found that although innate lymphoid cells are found
throughout the intestine, they seem to perform speciic roles that
are critical for caecal health. It’s already known that innate
lymphoid cells produce a number of signalling molecules that
are very important for regulating inlammation and tissue repair.
Some of these pathways could be involved in this protective
circuit. Unlike humans, mice don’t themselves have an appendix,
but this system now provides a model in which we can system-
atically start to investigate what is happening in the different
parts of the gut, in particular the caecum.The Future
The genomics revolution has ushered in a very exciting phase
in understanding how the gut works, how immune cells impact
on its function, and how man and microbes coexist to maintain
the health of the body. These technological advances will allow
us to assemble a much more complete picture of how immune
cells interact with the different compartments of the digestive
tract. Importantly we hope to understand how this affects the
health of an animal and how we might manage a number of
health problems associated with disorders of the intestine,
including inlammatory disease, allergy, obesity and diabetes.
Lucille Rankin is now a Postdoctoral Fellow at Weill Cornell Medical College. Gabrielle Belz
is a Laboratory Head at the Walter and Eliza Hall Institute of Medical Research.JUNE 2016|| 29... the good bacteria
harboured in the
appendix provide a site
where the body’s own
microbial culture is
sequestered so that it can
repopulate the gut after
the infection is over.