During the second half of the semester, Dr. Hemraj presented
his research on evidence that microbiomes have a role in the development of
A-Beta protein deposits and microglia phenotypes typical of Alzheimer’s disease
in a sex-specific manner in mice. His research is part of a novel field that
has only recently been brought to the spotlight and has begun gaining traction
in news articles and opened a new market in consumer health products. Dr.
Hemraj’s research was particularly interesting because it showed how male mice
with differing microbiomes had significant changes in the typical progression
of A-Beta amyloidosis and microglia phenotypes that are markers for Alzheimer’s
disease. Male mice that was given an antibiotic cocktail from birth was shown
to have a wildly different gut microbiome than a wildtype mouse as well as
significantly less, if any of the markers for Alzheimer’s. In addition, upon
transferring a wild-type mouse’s fecal matter to an antibiotic treated mouse,
you could induce changes to the recipient and ‘rescue’ the wild-type condition.
This fecal-transplant mouse would once again exhibit higher markers of Alzheimer’s
than the antibiotic treated mice who did not receive transplants. Essentially,
this research meant that there was something about the wild-types gut flora and
diversity of bacteria, which is absent in the experimental mouse, that was
producing the progression of Alzheimer’s in male mice. This research is quite
thought provoking and in fact was mentioned in The New York Times article Germs
in Your Gut Are Talking to Your Brain. Scientists Want to Know What They’re
Saying (Carl Zimmer) along with a few other similar research papers done by
differing groups. Since the goal of the blog is to avoid an article referencing
the research, I’ll strictly stick to the section regarding the other research
that has been done in this field. First off, the author introduces this field
as exactly what Dr. Hemraj was explaining that the idea of researching the
microbiome in relation to disease and behavior was ‘considered crazy’ as for a
long time we weren’t able to preserve the entirety of an animals gut flora in vitro.
The author quotes Dr. Rob Knight of UC San Diego that “As recently as 2011, it
was considered crazy to look for associations between the microbiome and
behavior.” Dr. Rob Knight was one of the earliest investigators in the field
and discovered that germ-free mice that received a fecal transplant from mice
with a genetic mutation that caused them to be overeat would begin overeating
and gaining weight. This sort of research shows that the microbiome is playing
a very complex role with our bodies and brain backing the idea that Alzheimer’s
could be due to the gut as much as genetic predispositions would, and maybe the
genetic predispositions are affecting the immune system – gut flora
interactions. The article additionally mentions research by Dr. Cryan who found
sterile mice to become loners and prefer staying away from fellow rodents. Not
only did Dr. Cryan find a behavioral change, but a significant change to the
amygdala, the center for emotional processing. According to Dr. Cryan the
amygdala of these germ-free mice made an unusual set of proteins, changing the
connectivity of these neurons. Evidently, being germ-free not only plays a role
in A-Beta clumps but also the genetic expression of neurons in the amygdala as
well. Further behavioral changes are found as we look at the gut flora of
humans and further, those with Autism, who have been shown to “Have unusual
patterns of microbial species in their stool” (Carl Zimmer). Researchers in
this field, like Dr. Sisodia and Dr. Hemraj are confident that these results
are due to the bacterial changes, however, the author brings up a good point of
the limitation to this research done so far. Because these researchers are transferring
hundreds of bacterial species at once in fecal transplants, the experiments don’t
have the ability to know what species the cause of the brain changes are
observed among all these studies. In addition, it is still somewhat unclear if
the disease is causing the changes to the gut flora or rather what these scientists
speculate: the opposite. As the author makes note, this uncertainty is due to
the known fact that those with Alzheimer’s change their diet as the disease
progresses, which could be responsible for changes in the gut flora as well. The
is one study discussed with some certainly though, and that’s one done by Dr.
Costa-Mattioli, who found that feeding mothers a high-fat diet makes it more
likely that their pups develop antisocial behaviors as previously seen in
SHANK3 mutant mice. When they compared the microbiomes of these mice, they
found a specific stain, Lactobacillus reuteri, which was lacking in both
populations. When this stain was added to either animals’ diet, the animals
became social again. The author quotes Dr. Consta-Mattioli’s statement that he “found
evident that L. reuteri releases compounds that send a signal to nerve endings
in the intestines. The Vagus nerve sends these signals from the gut to the
brain, where they alter production of a hormone called oxytocin that promotes
social bonds.” The author states that research points to the gut microbiome
developing before birth as a pregnant mother’s own microbiome releases molecules
that enter the fetal brain as well as other research showing a seeding of
microbes during childbirth and breast feeding. The final section of this
article shows further research showing the microbiomes impact on both epileptic
and Parkinson type symptoms in mice. The author depicts these researchers new struggle
to not be overly enthusiastic about these results as they may be skewed by the
media and the reality is that we’re only just starting to get a glimpse of what’s
going on. The author depicts the problems with emerging OTC probiotic
supplements and the pseudoscience claims of curing depression among other
diseases they have begun to claim. There is still more to be done in research to
figure out what strains should be included in these probiotics and at what dose
which will require many clinical trials. While research like Dr. Hemraj and
others are showing to be quite significant in their effects on our nervous
system, its too early to buy into PR campaigns that are based off these first
signs of importance. The science still has much time to mature, but it is interesting
nonetheless.
https://www.nytimes.com/2019/01/28/health/microbiome-brain-behavior-dementia.html
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