The gut, the nerves, and the microbiome

The human body has around 100 trillion microorganisms. The microbes living within our gut usually live in harmony and help with a variety of important biological functions. Research shows our genes influence our microbes. Our microbes support our neurons, and when imbalanced we might develop certain diseases.

Our microbes used to be thought of as opportunistic invading pathogens, now we are starting to see them in a new light. Animal models engineered to have the brain disease autism have microbes missing from their gut. The mice also behave better when their missing microbes are put back. To test the idea that probiotic bacteria could potentially improve brain function, in 2018 the National Institutes of Health awarded Dr. Frances Lefcort $2.9 million dollar grant award to study the microbiome in FD.

Frances Lefcort and Sarah Ohlen Neurology Research
Dr Frances Lefcort, who was awarded a grant from the NIH to study the microbiome in patients with familial dysautonomia

We also know that the gastrointestinal tract doesn’t function the way it should in FD. Patients suffer from an array of problems like constipation, diarrhea, reflux and bloating. If the 100 million neurons living in the gut could be influenced by the microbiome, this raises the prospect of making sure the microbiome is optimized to the nerve cells survive and function.

While the sophisticated analytics to profile the microbiome requires cutting edge technologies, getting patients to participate fell into the hands of one scientist at the Center. For the last year, Dr. Maria Cotrina has been sending patients stool collection kits and asking their relatives to be controls. At the clinic, patients and relatives give a blood sample to examine their metabolomics. For many patients, the highlight of their visit is seeing their family members also participating in the research too.

Dr. Cotrina, who has an interest in metabolic diseases, was the perfect person to run the project. She sits in on all the yearly check-up visits, notes down any gastrointestinal issues the patients speak about, and goes over with each family what they eat and when. Her attention to detail means that when it comes to interpreting the microbiome data, it will be possible to connect the findings back to that specific patient at that moment in time. We know that the microbiome is influenced by your environment, your genes, your diet, when you last took antibiotics, which is why she collects this crucial information.

For many years, the diets of FD patients have been something that staff at the Center have been grappling with. There are patients that tell us they avoid certain foods hoping they’ll feel better, but this is not always without risk.

Dr. Maria Cotrina, who runs the project at the NYU Dysautonomia Center

A few years ago, specialists in FD around the world began seeing patients with extreme malnutrition caused by eating only very restricted diets. The idea came from avoiding foods with high tyramine, which you can do by skipping things like fermented cheese or Chianti wine. Unfortunately, instead, patients were led into restricting tyrosine, which is a vital amino-acid. The first oath of medicine is to do no harm.  Before telling people with FD what they should or should not eat, we first need to understand what patients do eat, if this changes the balance of gut flora, and whether this has a downstream effect on the millions of tiny enteric neurons that are responsible for the functioning of the gut and beyond that.

For Dr. Cotrina and staff at the Center, the NIH-funded microbiome project has become a chance to dive deeper into understanding the gut in FD. Finding the right diet can be a long process involving nutritionists, gastroenterologists, and a lot of trial and error. Finding potential ways to restore the function of the nerves by tweaking the microbiome is an exciting avenue to explore.

Stay tuned to hear about our progress ….

Funding: National Institutes of Heath (R 01)