The Microbiome Podcast returns: Episode 10 with Dr. John Cryan on the gut-brain axis

The Microbiome Podcast has been on a hiatus since June so we wanted to make sure that our first episode back was a good one.  Our conversation with Dr. John Cryan from University College Cork in Ireland was very informative and for anyone interested in how the microbiome and the gut may impact the brain during development or in later stages of life, this is a great listen. 

Listen to the episode on our website. On iTunes. On Stitcher. 

On this week’s episode we discussed: 

• (1:06) Our visit to the White House and the Office of Science and Technology Policy’s microbiome initiative.
• (3:30) A paper describing the “microbial cloud” that individuals emit. Read the paper.
• (6:18) A C. diff treatment that ReBiotix received breakthrough designation from the FDA. Read more. 
• (9:04) We were joined by Dr. John Cryan.  
• (9:20) What is the gut-brain axis?
• (12:00) The importance of the gut-brain axis during early stages of life.
• (13:35) Studies in humans that show how the microbiome may influence brain function. A study from Mike Baley's group on temperament during early childhood. 
• (15:20) Psychobiotics.
• (22:45) The gut-brain axis in neurodegenerative diseases like Parkinson’s and Alzheimer’s disease. A study from Denmark that showed if a person had their vagal nerve removed halved their chances of getting Parkinson’s disease. 
• (27:40) Microbiome mediating hunger and a specific hormone called ghrelin.
• (32:40) Research in the Cryan Lab. Read more. 
• (37:05) The APC Microbiome Institute at University College Cork. Learn more. 
• (41:00) On the aftershow, we discussed our opinions of iPhones and Apple products.

A brief summary of a recent review of the gut-brain axis

Comparison of a normal aged brain (left) and the brain of a person with Alzheimer's (right). 

The gut-brain axis refers to the interplay between the gut microbiome and our behavior.  There are a few mechanisms by which the gut microbiome can affect the brain, such as by directly communicating with it via the vagus nerve, by producing hormones or other metabolites that influence brain function, and by eliciting a systemic inflammatory response.  This past month researchers Timothy G. Dignan and John F. Cryan, both of the University College Cork, in Cork, Ireland, published a review of the recent advances in the gut-brain axis literature.  Many exciting scientific developments have occurred in the past few years, including new advances that connect the microbiome with depression, autism, Alzheimer’s disease, and schizophrenia.  Here, we discuss some of those studies and summarizing the review.

Depression: Studies have shown a possible association between the microbiome and feelings of depression.  It is not clear, however, if these changes are due to drugs that are being taken.  Other studies have shown that probiotics can reduce thoughts of depression, and a separate study showed that eating yogurt improved the moods of oil workers.

Autism:  Again, research has shown a correlation between the microbiome and autism, but not any sort of cause or relation with symptoms.  Multiple studies in mice have shown that a dysbiotic microbiome can lead to autism like symptoms, and that altering the microbiome can alleviate them.  Again, however, there are few mechanistic links between the microbiome and the disease.

Alzheimer’s disease:  Very few studies have linked Alzheimer’s and the microbiome.  Some studies have seen a broad decline in microbiome diversity amongst Alzheimer’s patients, but decreased diversity is known to be associated with many other phenotypes.  Smaller studies on mice have shown some symptoms of Alzheimer’s, such as memory loss, can be somewhat reversed using probiotics, but the results are hardly robust and do not necessarily imply a link with Alzheimer’s.

Schizophrenia:  Like Alzheimer’s, very few studies have linked the microbiome and schizophrenia.  Like all of the above, various associations have been made between the disease and the microbiome, but no strong correlations have been measured.  In mouse models of schizophrenia, antibiotics can alleviate symptoms of the disease.  In addition, there is evidence that antibiotics can also improve the mental state of humans. 

Taken collectively, there is a compelling reason to believe that the microbiome is important to each of these indications, and that it is critical to a healthy mind.  It is still early days though, and much more research is needed to prove mechanisms and pathways.  

Episode 6 of The Microbiome Podcast: The microbiome, autism, and serotonin production with Dr. Elaine Hsiao

The sixth episode of The Microbiome Podcast is now available. We had a great chat with Dr. Elaine Hsiao, a new professor at California Institute of Technology. Elaine was the first author on the seminal paper from 2013 that showed a connection in mice of the microbiome and autism spectrum disorder related behaviors. We talked with her about that work as well as more recent work that she published from her own laboratory describing the microbiome’s role in regulating serotonin production.

Listen to the podcast here on our website. Here on iTunes. And here on Stitcher. 

Below are more detailed show notes:

• (2:20) Last week’s guests Erica and Justin Sonnenburg were featured in a New York Magazine article. Read the article. 
• (3:48) The Gates Foundation’s Grand Challenges in Global Health launched a grand challenge titled Addressing Newborn and Infant Gut Health Through Bacteriophage-Mediated Microbiome Engineering. Learn more. 
• (6:22) uBiome launched a clinical laboratory. Read more. 
• (7:56) Second Genome partnered with the University of Cork in Ireland to develop therapies for inflammatory bowel diseases. Read more.
• (9:02) Dupont recently acquired Taxon Biosciences, a microbiome company. Read more. 
• (11:15) A caller asked how long his microbiome would take to recover to it’s previous state after taking antibiotics. We based the answer on a paper by David Relman published in 2010. Read the paper.
• (16:19) We start the interview with Elaine Hsiao. Check out her laboratory webpage.
• (18:00) We talked with Elaine about her seminal paper on the microbiome and it’s possible connection to autism spectrum disorders. Read the paper.
• (31:06) We talked with Elaine about her recent paper showing that gut bacteria are important for production of serotonin. Read the paper.

We will be back in two weeks with Drs. Eugene Chang and Vanessa Leone from the University of Chicago discussing how the microbiome may be involved in the complex relationship between disruptions to circadian rhythms and obesity. Please call in with any questions for Bill and David or for Drs. Chang and Leone to 518-945-8583. 

The role of the gut microbiome in Down Syndrome

Down Syndrome is the most common genetic cause of intellectual disability and occurs when there is an extra 21st chromosome, trisomy 21. Down Syndrome patients often experience premature aging and are therefore at early risk for age-related conditions like Alzheimer’s disease. Scientists from Italy published a study in November in PLOS One that compared the gut microbiome of Down Syndrome patients with that of healthy individuals.

The scientists hypothesized that the gut microbiome of Down Syndrome (DS) patients was contributing to the aging of the patients and would present similarly to the microbiome of an aged individual. They compared the gut microbiome of 17 patients with DS with previously published data for 16 age-matched individuals as well as 5 elderly individuals and 3 individuals who were 100 years old.  Interestingly, they found that the microbiomes of patients with DS were very similar to the microbiomes of healthy individuals. In this case, their hypothesis did not end up as they predicted. 

It is important to note that this study only included 17 test subjects who were all under the age of 35.  Future studies will need to be conducted with larger patient cohorts as well as older patients to truly get a good understanding of the gut microbiome profiles of the entire population of patients and better understand this hypothesis. 

There was, however, an unexpected finding that I found to be quite interesting. While the general makeup of the DS patients' microbiomes were similar to those of healthy individuals, there were subpopulations of bacteria that were more or less abundant in DS patients. Individuals with DS had elevated levels of Parasporobacterium and Sutterella and reduced levels of Veilonellaceae. This increase of Sutterella and decrease of Veilonellaceae has previously been described in autistic children with stomach problems. Specifically in this study, Sutterella abundance was positively correlated with Aberrant Behavior Checklist (ABC) scores for the DS individuals. The ABC test is a 58 item report checklist used to assess maladaptive behavior in people with developmental disabilities. 

This positive correlation tells us that this bacterium in the gut may play a role in maladaptive behavior in patients with various conditions. Although the original hypothesis was not confirmed, this very interesting result will need to be further explored to better understand the role of the gut microbiome in individuals with autism spectrum disorder and Down Syndrome.

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.