The microbiome and autism

I want to discuss a really important paper from December 2013 published in Cell by the Mazmanian lab at Cal Tech that links the microbiome to autism spectrum disorders (ASD).  We already know that there is link that is becoming well-established between the gut and behavior.  It has also been shown by other researchers that humans with autism also have high levels of IBD and other intestinal disorders.  This suggests microbiome dysbiosis may be linked to autism, and was the motivation for this research.

In the paper the researchers induced ASD symptoms in mice by using a known method in which  a mother is infected with a virus-like molecule, and the offspring of that mouse have a high likelihood of having ASD symptoms.  After doing this procedure they directly demonstrated that those mice with ASD symptoms had reduced GI tract integrity, and had elevated levels of some metabolites in their blood when compared to offspring mice from the same mothers without ASD symptoms.  Furthermore, some of the metabolites that were elevated are thought to be biomarkers for autism in humans (they are also elevated in humans with autism).  Finally, when the offspring mice with ASD symptoms were given a probiotic, their symptoms were reduced, and those same metabolites were also reduced.  

This research is especially exciting given that the probiotics were therapeutic for mice already displaying ASD symptoms, suggesting a possible cure for autism, but obviously let's not get ahead of ourselves. 

A nice round-up of the article, which was co-authored by our friend Rob Knight, has a great summary of research, and I suggest anyone with further interest to read it.

The great fecal microbiota transplant debate

An article was published today in the Atlantic that does a really nice job of describing the controversy surrounding fecal microbiota transplants (FMTs).  Basically, FMTs have been highly effective (>90% effective) in treating C. Difficile infections, and this efficacy has been even used as proof of the causal role of dysbiosis in C. Diff infection.  

The problem though, is that FMTs are currently unregulated, and the real question is how does the FDA regulate this new treatment, especially with how little is known about the microbiome.  The first question the FDA has to answer is whether or not fecal microbiota is a drug or a tissue.  Currently it is considered a drug but many common definitions would call it a tissue.

In addition, no one knows any long term consequences with FMTs, or what diseases to look for in donors, or how to screen FMTs at all.  Fecal microbiota is obtained just as you would imagine, through stool samples, and everything in that stool is transferred, the entire microbiota, including viruses.  It is a really complex issue that comes down to ethics, the responsibility of government, and the science of the microbiome.  Without guidance though, many have resorted to DIY FMTs which is not a good idea!

At the AMI we are aligned with the editorial written by a consortium of microbiome scientists, including our very own Marty Blaser and Rob Knight.  They support the FDA's cautious approach and note that past transplant procedures, like with blood, have resulted in unexpected disease transfer.  They also do see the benefit of FMTs and want to move forward with research to develop proper protocols, registries, and databases, as well as thorough clinical trials.  

A fellow non-profit here in Cambridge, Open Biome, based out of Eric Alm's lab at MIT, has created the first stool bank.  Organizations such as this will be essential to centralizing data and clinical outcomes, and we support their efforts.

Finally, drugs are being developed for C. Diff infection that are working.  Seres Health is a start-up in Cambridge, that has had great success in an oral treatment to C. Diff.  This may very well be the treatment for C. Diff in the future, but with so many diseases being linked to the microbiome, FMTs will again be at the forefront of therapeutics, even if they have not been successful for more complex diseases such as IBS and ulcerative colitis.

The gut-brain axis - microbiome and depression

Today I will be discussing a review from a little more than a year ago that discusses research that links the microbiome with stress, anxiety, and depression.

First, it should be noted that a 2-way communication between the gut and brain has already been established.  The review goes on to mention studies in mice where not only are germ free mice associated with higher stress responses, but stress and anxiety early in life are associated with long-term changes in the microbiome.  There was efficacy in reducing stress by treating stressed mice with probiotics.  Other studies however have shown germ-free mice to have reduced stress when compared to their counterparts.  In addition, multiple studies showed that inflammation of the gut caused by dysbiosis or a pathogenic gut bacteria increased stress and anxiety levels in mice.

There are many mechanisms by which the microbiome communicates with the brain and may affect the stress levels.  I encourage anyone interested to read the paper to learn more.  In the end, more research is needed to discover just how important the microbiome is to our mental health.

The microbiome and vaccine effectiveness

The relationship between the development of the immune system and the microbiome has long been the subject research, and many scientists believe that a healthy microbiome is essential to a strong immune system.  This type of research is normally performed on infants and toddlers because those years are the most critical for the immune system.  It is no surprise, that many scientists feel the microbiome may also be influencing how the immune system responds to vaccines, and a new review in Trends in Immunology presents many ways in which the microbiome has already been linked to vaccine effectiveness, as well as other mechanisms by which the microbiome could be impacting vaccine effectiveness.  The article also calls for more research to be performed on this link.

The review comments on studies which show that oral vaccines are not as effective in areas of the world where malnutrition is common, and the review suggests the microbiome to be the cause.  The authors suggest that new adjuvants could take advantage of the microbiome, and even suggest the use of microbiome derived molecules for use in adjuvants.

Home is where the heart...and microbiome is.

A fascinating study was published today in the journal Science that discusses the results of the home microbiome project.   The study tracked 7 families over the course of 6 weeks and sampled the microbiome of their homes, hotel rooms, and everywhere else they resided (3 of the families moved homes in the 6 week period).  They then linked these microbiomes with the hand, nose and feet microbiomes of the people who lived in each space.  The results showed that wherever we go, we take our microbiomes with us.  Basically, when moving to a new home, within days the microbiome of that family is established in the new abode (very rapid!), and was stable thereafter.  These bacteria are not random; they come directly from our hands, feet, and other areas of contact between our bodies and our environment.  Furthermore, there is variation between the microbiomes of each family and their home, meaning that a home microbiome could act as an identifying characteristic (fingerprint) as to who lives there.

Some other notes from the study, the floor microbiomes of our homes vary the most.  If you share a home you have similar hand microbiomes as those you share with.  Couples share more of a microbiome than individuals who are merely living together, but cohabitating does increase similarity in microbiome.

This work, along with many other studies, is happening because of the microbiome of the built environment project (MoBE) created and funded by the Alfred P. Sloan Foundation.   As the United States and world continue the trend towards urbanization it is vital to learn about the microbiome of the environment we create and interact with, and how this can affect our health.  So far the major findings from the MoBE project have demonstrated that the microbiome where we live looks an awful lot like our microbiome!

Editors note: I wonder if this home microbiome contributes to the fact that homes smell differently depending on who lives there?

Pregnancy and the microbiome

There have been a number of studies that discuss the importance of the microbiome transfer between mother and child; however few studies have looked into the changes that occur to the mother's vaginal microbiome during pregnancy.

A new paper published in the journal Microbiome by AMI Scientific Advisory Board member Dr. Jacques Ravel of the University of Maryland School of Medicine presents a longitudinal study of the vaginal microbiome of women during the course of pregnancy and compared that with women who were not pregnant.  The overall findings of the study conclude that there are statistically significant differences in the vaginal bacterial populations between pregnant and non-pregnant women.  Furthermore, the microbiome of pregnant women was more stable in non-pregnant women.

While there is a difference in the microbiome between pregnant and non-pregnant women, the authors stress that this difference in microbiomes may NOT be exclusive to pregnancy; therefore  at this point, not suitable for diagnostic purposes (say determining pregancy).  Furthermore, it is not known if these differences in any way benefit pregnant women or are just the result of different vaginal environments, for example higher estrogen levels in the vagina.

Finally, another paper that was possibly from the same longitudinal study showed no statistical connection between the vaginal microbiomes of women who go into pre-term labor and those who carry their child full term.