This research article is titled "Sinus Microbiome Diversity Depletion and Corynebacterium tuberculostearicum
Enrichment Mediates Rhinosinusitis".
It was published by Susan Lynch's group at the University of California in San Francisco
in Sept 2012 in Science Translational Medicine.
It may be surprising for some of you to hear that our bodies are not only composed of human
cells but we are in fact made up of MORE bacterial cells than human cells!!
The collection of bacteria that live in our bodies (on our skin, in our intestinal tract,
lungs, mouth, etc.) are termed "the human microbiome" . Although some bacteria can cause
disease, the bacteria that compose our microbiome are for the most part harmless.
So what is their purpose?
Why have we evolved to act as a host to so many bacteria?
Well, the role that this microbiome is playing with regards to our health is only now starting
to emerge thanks to new technological breakthroughs that I will come back to.
But before I do, It's important to understand that our microbiome is composed of bacteria,
fungi and viruses but we'll focus on bacteria for now.
in the microbiome there are VERY MANY different species of bacteria.
and its composition is ever changing and can be influenced by many factors: for example
what we eat, viral infections, our immune state, our general health, genetics etc. so
as you can see it's often very difficult to analyze changes in the microbiome because
its composition can vary A LOT from person to person and from time to time.
The lynch lab aimed to study the microbiome composition in the sinuses of patients affected
with chronic sinusitis.
Chronic sunisitis affects more than 30 million americans and is defined as a state of chronic
inflammation of the sinuses.
We are not exactly sure what causes sinusitis but some have speculated: allergies, nasal
polyps, bacterial, viral, or fungal infections, which as you can see if not very specific
and for the most part we are not very sure of the exact cause...
So how do we treat sinusitis in the clinic?
Because CS is a state of chronic inflammation, treatments include steroids which reduce inflammation,
antibiotics to kill bacteria that may be causing disease in the sinuses, or surgery, but this
is often not effective in the long term and symptoms tend to reappear.
so as you can see, we still have a lot to learn about the cause and mechanism of disease
to provide more targeted and effective therapies.
So in this study, the scientists isolated bacteria from the sinuses of patients that
happened to be undergoing sinus surgery for a variety of reasons.
They collected samples from 10 patients with CS and 10 patients without CS and looked at
the types & abundance of bacteria that were present in each patient using an advanced
method able to measure the abundance of over 8500 different bacterial species.
What the scientists found was that the sinus microbiome of CS patients was very different
than that of healthy patients:
The sinus micorbiome of healthy patients had a wide variety of different bacterial species
And the distribution of the bacteria was very even throughout all of the different species.
This is typical of what is thought to represent a healthy microbiome: one in which many different
species are represented and evenly distributed among the different groups
In contrast:
The sinus microbiome of CS patients had much fewer different types of bacteria
The distribution of the bacteria in the different species was very uneven (dominated by few
organism)
Overall, the sinus microbiome of CS patients was much less diverse than that of healthy
patients.
What was most surprising though was the over abundance of a specific type of bacteria:
CT in CS patients compared to healthy patients.
Healthy patients also had CT bacteria in their sinuses but it was not as abundant as in CS
patients.
In fact, CT bacteria is very abundant on normal human skin as part of the skin microbiome,
so it's surprising that CS patients have A LARGE amount of this bacteria in their sinuses
... Prior to this study CT had never been thought of as a pathogen, but merely as a
harmless resident bacteria of the skin.
Next, the scientists were interested in seeing if the abundance of CT in the sinuses of CS
patients could potentially be causing sinusitis symptoms.
To do this, they used the mouse as a disease model.
They treated the mice a few different ways:
1 - untreated mice
2 - since most CS patients receive antibiotic tx, they treated a group of mice with antibiotics
alone
3 - mice treated with CT alone
4 - mice treated with CT and antibiotics.
so what did they find?
Well, mice in groups 1 &2 did not develop sinusitis-like symptoms, as expected.
however, mice in group 3 developed more mucous secretion, which is a hallmark of CS and their
microbiome contained more CT bacteria.
And surprisingly, mice in group 4 had EVEN MORE mucous secretion in the sinus cavities...
so what does this mean?
First of all, this means that CT is able to induce sinusitis symptoms when present in
overabundance.
This would explain why antibiotic treatment can temporarily alleviate symptoms in CS patients,
by killing off all of the bacteria, including the CT bacteria.
But how could the presence of antibiotics in combination with CT actually worsten the
sinusitis symptoms?
Well, the scientists postulate that the antibiotics are able to clear the microbiome from the
sinuses and that this provides an opportunity for the added CT bacteria to take over and
grow better.
This suggests that something in the sinus microbiome may actually be preventing CT from
growing too much and producing very severe symptoms.
In fact, there was one bacterial species that was greatly REDUCED in abundance in CS patients
compared to healthy patients: L Sakei.
when the scientists added both LS and CT in the sinuses of antibiotic-treated mice, no
sinusitis symptoms developed...
this proved that L.sakei prevents CT from growing too much.
This is very surprising!!
because it highlights the incredible level of competition that occurs in the microbiome
between different species to maintain a healthy balanced state and prevent outgrowth of single
species which may affect the health of the patient (in this case CT).
So what did this study show?
Overall, this study provides both a model for the development of sinusitis, and a potential
treatment.
1- According to this study, CS may be caused by the overabundance of CT in the sinuses,
which somehow triggers activation of the immune system, skewing the body towards an inflammatory
state.
CT is found in normal healthy people so its presence is NOT pathogenic, what's pathogenic
is its overabundance.
Q1- Exactly HOW CT ends up becoming so abundant is unclear, but it could be due to a viral
infection, a weakened immune state, such as fatigue or some underlying disease, or antibiotics
which clear the microbiome giving a few species the opportunity to grow and become highly
abundant.
Q2- Also, its unclear HOW the overabundance of CT activates the immune system.
this will be an interesting question to follow up on.
2- According to this study, treatment with antibiotics, although it works in the short
term, could be detrimental in the long term because it could clear away some of the bacterial
species that are trying to keep CT in check and may in the long-term allow for an even
greater opportunity for CT to grow and induce more inflammation and stronger sinusitis symptoms!!
3- An alternative treatment for CS may actually be to supplement the sinusitis microbiome
which has very low diversity, by adding more LS, to try to return the microbiome to a healthy
balanced state.
What's also very impressive in this study is that, despite the amazing diversity of
everyone's microbiome, the scientists were still able to find ONE SINGLE species that
was over abundant (corynebacteria) that seemed to cause CS and ONE SINGLE species that was
depleted (l.sakei) that seemed to protect from CS in patients!!
So what does this mean to you?
This all sounds great as a model for the cause and treatment of sinusitis and it certainly
worked in their mouse system.
However, the scientists induced sinusitis solely by providing CT in the mouse sinuses.
this may not be the ONLY cause of sinusitis in humans, and it's definitely possible that
other bacterial species, viruses, or fungi could also contribute to causing sinusitis.
in which case, addition of LS may not be all that effective in all cases.
Also, CT may be providing some benefits when at normal levels as part of a health microbiome...
suggested by its presence in healthy people so its total elimination may be bad.
Empashing the importance of a balanced/diverse microbiome composition
Lastly, it's important to be cautious in our use of antibiotics because we may be killing
off some good bacteria and allowing a few species to outgrow, which decreases the diversity
of our microbiome and could be detrimental to our health.
All together, this study does provide overwhelming evidence that the search for a greater understanding
of the role of microbiome communities in our health could lead to some very interesting
discoveries related to the causes of disease, especially those involving inflammation.
these discoveries then provide a basis for the design of targeted therapies for a diseased
microbiome as this article demonstrates.
Thinking ahead, it may even be possible to profile an individual patient's microbiome
and determine which species are depleted or overabundant in that individual patient that
may be causing their disease; a step forward for personalized medicine.