Our body is made up of trillions of cells that
contain our own DNA.
However,
there are even more cells
that originated from outside our bodies that are currently living
within us, serving several important functions.
The human gut contains the highest density of microorganisms
in the whole human body,
and collectively, these organisms are referred to
as the gut microbiome.
This video will take a look at what the gut
microbiome, and explore
how learning more about
it could potentially hold the key to understanding and treating
many different gastrointestinal diseases.
This video has been made in consultation with
Dr. Nikhil Pai, who is an associate professor in the division of
Pediatric Gastroenterology and the medical lead of the Complex
Pediatric Nutrition Services at McMaster Children's Hospital.
He is also a principal investigator studying the role of
the intestinal microbiome
in gastrointestinal
health and disease.
Let us first hear from him about what exactly the
gut microbiome is
and the nature of the relationship between us and these
bacteria.
So what the gut microbiome or microbiota is,
is sort of like this parasite,
you could say,
but probably more like
a parasite that has like a symbiotic relationship with
us, thanks to various things that we give that bacteria,
fungi, and viruses,
in our intestines
-largely through way of food
by eating, ourselves.
All of those things get processed by the gut microbiota,
all the different bacteria,
viruses, and organisms
and they produce their own proteins and
metabolites. Sometimes those proteins and metabolites get absorbed by
us and actually end up influencing our own bodies.
It helps us have our normal physiology,
thanks to some of its functions,
thanks to the contributions
we give it,
and ultimately
kind of controls the way that we experienced health and
disease.
The importance of a healthy microbiome often gets overlooked,
however,
when improperly
balanced and left in an unhealthy state,
it's hard to ignore the pain and illness
as a result. Within our gut there exists
both 'good' and 'bad' microbes. Typically these cohabit in balance
and create a symbiotic relationship within us.
Microbes are able to perform important metabolic and immune functions.
However,
if this balance is disturbed, dysbiosis occurs
which may cause weight gain, inflammation, and allergic responses.
Though,
in more drastic cases
it can also lead to diabetes,
inflammatory bowel disease, and cancer.
So,
what does an expert classifiy as a healthy microbiome?
A healthy microbiome is one that is diverse and rich. That makes it a little more resilient to outside stresses.
However, the creation of a healthy gut microbiome can be slightly
more challenging to predict. This is because individually we all
have unique microbiomes of over 100 trillion microbes, of which
the ratios of such microbes depend on factors
including genetics, environmental factors, medication,
exercise, and diet.
If the microbiome is supposed to be sort of like an ecosystem
-and I thnk that we can all agree like, when you look at the Amazon rainforest or something that's
like very
rich and diverse- probably,
when you have a lot of different species, with a
lot of different kinds,
they're able to kind of be referees for each
other and keep things in check.
So it's a maybe when you have too much bacteria
of any one particular type,
then it can run a little rampant and that can
potentially be a problem.
This whole idea of like the diverse ecosystem,
the rainforest,
its so beautiful and rich and all the rest.
Then you realize that actually,
even though there's a couple of bacterial species that are
in very low
abundance, relative to
everything else they are
super metabolically active and they are like these keystone species
_
They are very, very rare but if you don't have those
the entire system goes awry.
The gut microbiome also interacts closely with the host immune system, where many autoimmune diseases have been linked to certain
gut microbiome profiles.
The gut microbiome
sort of piggybacks
the immune system and assists in immune responses to fight off disease.
A strong immune response to fight off
diseases,
requires energy.
This energy depends on your metabolism.
Think of your metabolism
as a campfire.
To fuel this fire you add logs or in this
case food.
During this process,
you make other intermediate chemicals called metabolites, which assist
in the making of the fire.
Microbes make immune responses
smoother with their ability to contribute these metabolites and fight
off disease with ease.
Though,
despite all efforts to maintain a healthy microbiome,
some diseases
and conditions can still persist. IBS or irritable bowel syndrome,
is one of the most widespread disorders of the gut,
resulting in uncomfortable
symptoms of gas,
painful cramps and abnormal bowel movements. More severe,
Crohn's Disease is a type of irritable bowel disease which
is characterized by inflammation of the digestive tract,
usually the small intestine and results in severe diarrhea, fatigue,
weight loss and malnutrition from insufficient nutrient absorption.
It is not yet known what exactly causes Crohn's Disease,
but scientists believe that an individual's immune response,
genetics, and environment
all play a key role in the severity of Crohn's
Disease.
Individuals with IBS, ulcerative colitis, and Crohn's have different
microbiome profiles,
compared to healthy individuals.
It has been established
that the microbiome plays a large role in overall gut health
and the outcomes of Crohn's Disease.
But how do we alter the composition of bacteria with
in the gut?
Some of the ways that we have tried to affect the bacteria and just try to change it up
is through antibiotics,
getting rid of things; probiotics, giving more of something
but in limited quantities; and probably like the sledgehammer approach,
fecal microbiota transplants, where you give just a huge volume
of healthy bacteria from at least
a healthy donor who doesn't have Crohn's Disease.
Hopefully,
that is as healthy as you get, and you just change
things up. That's kind of a third way that
you can try and
use microbial treatments.
Fecal
transplants are a way to alter the composition of one's microbiome.
They involve the transfer of stool from one organism to another.
Where stool is transferred into the gastrointestinal
tract. Fecal
transplants have been extremely useful for resolving
Clostridium
difficile infections,
and they have also been linked to having positive results
with sclerosis,
increasing
insulin sensitivity,
and treating individuals with Crohn's Disease.
Fecal transplants are an effective way to replace 'bad' bacteria,
that may be causing complications, with healthy bacteria.
I think that's kind of goal number one, when you
do this, can you somehow take a child who is having fulminant symptoms
and just get them feeling better.
And that really
was the state of where we were, like we were
the first group to do a trial of this in
children, worldwide. Step two and three, though, is now saying well
what are we doing?
So we were able to show effect and these kids got better.
So now, what is it that's changing?
And I think the value of that is also to take
this to the next level.
If we can say what's changing, and
more importantly what consistently changes between like, if you both had
an FMT (Fecal Microbiota Transplant),
both of you got better.
And incidentally,
the same bacteria that were there in both of you
when you felt terrible are now gone,
maybe that's a clue.
Right?
Maybe those bacteria
were the ones that were causing problems.
It does seem that there are certain bacteria that
tend to be more pathogenic
and one term is pathobionts
in Crohn's Disease, that present themselves.
The flip side though is
also replenishing bacteria
that tend to be less abundant in these situations
and amongst them are often ones that produce certain
metabolites that are beneficial such as short-chain
fatty acid producing bacteria.
Short-chain fatty acids are great in normal, like everyday
state of physiology and incidentally tend to be depleted in
patients who have active Crohn's Disease.
So if we can try and give back those bacteria that
are short-chain fatty acid
producers, that maybe good. But
going back though to the earlier thing
we said,
you know,
it's kind of like a,
big auditorium or like this library.
If there's so many other loud
rowdy people who are taking up chairs,
you need to get rid of those first,
if the healthy and short-chain fatty acid
producing bacteria,
are able to take up residence without being shouldered out
and kept out of being able to take
up residence.
So, essentially what's called filling a microbial
niche.
So I think that's where FMT aims to do a little
bit of both.
Get enough of the good bacteria in, that they
cannot only dominate in terms of number,
but also hopefully shoulder out the more pathogenic organisms as well.
Fecal transplants can vary in length,
however,
more research is still needed in order to improve treatment
options.
Dr. Pai explains how the number of transplants may differ amongst different patients
We were giving 12 treatments over the span of 6 weeks.
We, our trial is one of the more frequent ones
that have been done in the patient,
but it still seemed that after 12 treatments,
we had a time point when they went up to 30
weeks, there were some patients,
who did well up until 30 weeks,
but then they started to show symptoms again.
So,
I think the issue is that like,
for some reason,
the microbiome tends to kind of bounce back to its
kind of pathologic state in many,
many, patients.
Although fecal transplants can be effective, there are still some limitations regarding their application and
the number of transplants needed. There has been some thought that maybe FMT
doesn't work
so well in people who are super sick,
who have really severe disease.
I guess I challenge that a little bit though,
because if you think about like the messy details of
how FMT's done, you're like
putting this liquid,
that has like a lot of healthy bacteria, or a
capsule
sometimes, into someone and hoping that it gets absorbed and
sticks. When you're really sick with Crohn's Disease or Ulcerative Colitis,
everything you take in is just pouring right through you.
So maybe it's not so much that they don't,
that it's not going to work,
but you need to treat them more frequently at the
beginning. And if only 10% of what I gave managed
to stick and
90% just went right down
the toilet, eventually, 10% is going to become 30% because
that's
like that really leaky sponge that's going to start to absorb
things better and then gradually,
it's going to become less and less frequent because what
you've given them is staying.
So,
so maybe going back to your question.
If you have milder disease,
perhaps you don't need to give it as frequently,
but when you are not doing so well,
you have to give a few back-to-back treatments.
Fecal transplants
also paved the way for bacterial infection treatments and can
pose as a viable option to reduce antibiotic use.
They can serve as a useful tool, especially with the
emerging issue of antibiotic resistance.
Fecal transplants also transmit various fungi and viruses,
like,
bacteriophages and eukaryotic viruses,
which impact the transplants efficacy. Host factors such as an
individual's age, diet,
and genetics,
can effect the efficacy of the transplant and the type of transparent used.
Though difficult to predict, a healthy microbiome can most easily be regulated
by diet. Eating fermented foods like yogurt, or prebiotic foods like bananas,
asparagus, and oats. As well as incorporating diverse types of food high in fibre
such as legumes and beans, can be beneficial.
Overall,
Fecal microbiota transplants
serve as an effective and viable option to alter gut
bacteria, that may be associated with Crohn's,
Disease. Further research can explore the implementation and effects of fecal transplants
on patient health.