Episode 20: Dr. Alessio Fasano discusses the gut microbiome and how it affects our health

Dr. Alessio Fasano // Sep 13, 2016

When Alessio Fasano entered medical school at the University of Naples (Italy) School of Medicine, his goal was to eliminate childhood diarrhea. Working with a mentor who’d studied the physiology of the gut, Fasano decided to focus on the microorganisms that cause diarrhea. That opened up his world to specialize in overall gut health, and Fasano became a leading expert in celiac disease and gluten-related disorders.

Following medical school, Fasano spent three years at the Center for Vaccine Development in Baltimore, and later returned to the U.S. to pursue his career. Today the world-renowned gastroenterologist is chair of pediatric gastroenterology and nutrition at Harvard Medical School and director of the Center for Celiac Research and Treatment. He is also the director of the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital.

Fasano was the lead researcher of a seminal 2003 study showing that 1 in 133 Americans have celiac disease, an autoimmune disorder characterized by gluten-induced damage to the small intestine. His book Gluten Freedom has been hailed as “the groundbreaking roadmap to a gluten-free lifestyle.” He is also the author of “A Clinical Guide to Gluten-Related Disorders.”

His lectures at IHMC “The Gut is Not Like Las Vegas,” (November 2014) and “People Shall Not Live by Bread Alone: People Shall Not Live by Bread Alone” have gotten over 70,000 views on YouTube.

Fasano has been featured widely in media, such as NPR, CNN and Bloomberg News. In this episode of STEM-Talk, Fasano talks about his early life as a curious boy in Italy, with a scientist grandfather as his first mentor, the impassioned trajectory of his career, and the underlying importance of gut health in determining our overall health.

00:56: Dawn describes Fasano as “a leading light in the study of the microbiome.” Fifteen years ago, Fasano and his colleagues discovered the pathophysiology of celiac disease and role of the protein zonulin in causing it.

1:10: Ford cites growing evidence that the microbiome content of the intestinal tract influences our metabolism, stress tolerance, immune response, memory and cognitive performance.

2:56: Ford reads five-star iTunes review of STEM-Talk entitled “cognitive satiety:” “Never have all the lobes of your brain been so satisfied. Every episode is fascinating and beautifully orchestrated. The content is interesting and diverse. There’s no room for boredom. The double secret selection committee does a superb job of keeping the listeners educated, engaged and more intelligent with every minute. And the hosts have a linguistic seduction that you wish it would never end. I could listen to STEM-Talk for hours. Thank you, and please keep the talks coming.”

3:51: Dawn introduces Fasano as a world-renowned pediatric gastroenterologist and research scientist. He specializes in treating people with celiac disease, wheat and gluten sensitivities, as well as infants and children with difficult to treat gastro-intestinal problems.

5:15: Dawn welcomes Alessio and Ken to the interview.

5:37: Fasano talks about his childhood in Italy. He was raised largely by his grandfather, a retired physicist who had once worked in Enrico Fermi’s lab. During World War II, Fasano’s grandfather refused to move to Germany as Mussolini had requested, so he ended up teaching high school science.

6:26: “I remember vividly being with him in his lab. [That] sparked an interest in physics and science.”

7:03: Fasano’s initial focus in medical school was eliminating childhood diarrhea— “not a glamorous field to get into.” At that time, five million people died annually from diarrhea, 80 percent of them children.

9:08: On his medical school mentor’s suggestion, Fasano went to the Center for Vaccine development in Baltimore to study micro-organisms in the gut. His two-month term became two years. Afterwards, he went back to Italy for a year and a half, returning to the U.S. in 1993, where he has been ever since.

9:47: Ken points out that Fasano has said that, “Twenty-five hundred years ago, Hippocrates posited all disease begins in gut: emerging understanding of the interplay between gut microbiome, intestinal mucosa and immune and nervous systems seems to support this contention.”

10:05: “Hippocrates was so right, without having all the information that we have right now,” Fasano says.

11:14: Fasano says that his thirty years of studying the gut have boiled down to the past five years, with the emergence of “the perfect storm of knowledge” about the microbiome.

11:50: The intestinal mucosa, a 3,000 square feet interface, negotiates cross-talk between us as human beings, the ecosystem, and our interaction with the environment.

12:30: Besides digesting food, the gut is involved in a continuous discussion with our environment, regulating the friends and foes that enter. The gut is the organ with the most immune cells; it’s also considered the body’s second brain, and has even more neuronal cells than brain itself.

13:28: The gut is a 20-foot-long tube. The epithelial cells interact with various types of immune cells.

16:00: The nervous system cells coordinate the interaction between the immune and epithelial cells, sometimes through messenger cells.

17:17: “Imagine all this decision making,” Fasano says. The epithelial cells have sensors that see who is in the lumen: friends, or if it’s foes, “You have to prepare for war.”

17:50: Commercial break: STEM-Talk is an educational service of the Florida Institute for Human and Machine Cognition, a not-for-profit research lab pioneering ground-breaking technologies aimed at leveraging human cognition, perception, locomotion and resilience.

18:33: Recent information indicates that the microbiome develops in the womb during the last trimester of pregnancy, but the major imprinting happens in the birth canal. That is why full-term, vaginal births are best for healthy microbiome development. Then other things—breastfeeding, for example—should occur to ensure sustained microbiome health.

22:05: The immune system developed to fight micro-organisms.

22:52: The microbiome teaches the immune system to work in a child’s first 1,000 days. A good, balanced microbiome is one that teaches the immune system to set the bar high for infections.

23:45: An unbalanced microbiome in infancy may be caused by the Western diet, C-section delivery, and infections. These things teach the immune system to have a low threshold for infections, placing infants at risk for chronic inflammatory diseases later in adulthood.

24:50: Fasano comments on the Human Genome Project: As humans, we have 23,000 genes, most of which we share with other animals; 95 percent of our genes are identical to a mouse. Only 400 genes distinguish us from chimpanzees. Other species have many more genes: Worms, for example, have 75,000 genes.

26:07: What are the implications of our relatively shallow gene pool? “We were not supposed to be dominant creatures on earth,” Fasano says.

26:53: Fasano explains his piano player analogy: Our 23,000 genes are like piano keys. There is an infinite combination of notes. The piano player is the microbiome that decides, based on genetic cross-talk, what notes should be played and when—just as genes express or suppress their activities.

28:10: Whereas previously, we were told that having the genes to develop diseases such as Alzheimer’s Disease, cancer, and multiple sclerosis determined our fate—that we would get those diseases—we now know that’s not true, Fasano says. “It all depends on our lifestyle; and how that affects our microbiome, which in turn affects which genes are turned on or off…. If I have the genes for Lou Gehrig’s disease, that does not mean I will get it. It depends on how I live my life.”

29:00: Until recently, we thought our disease destiny was determined by our piano player—assumed to be an outside. Now we understand that the piano player—our microbiome—is living inside of us.

29:57: Now the questions that we can ask are: What kind of player is there? What kind of music does he play? What kind of music is playing as we speak? “Doing mathematical modeling, we can predict if playing certain kind of music, you will end up with that kind of clinical outcome.”

30:48: “We cannot manipulate our genes, but we may eventually be able to manipulate our microbiome so we can keep ourselves healthy for a much longer period of time.” This is primary prevention; or precision medicine.

31:34: Ken comments: “This interaction between our genome and the microbiome is the part that I find most interesting and hopeful for the future. It explains the riddle of how a simple genome produces such a highly differentiated and complex animal; and opens up new pathways for medicine and human performance and resilience.”

32:10: “This is the best time to be in science,” Fasano says. “Technology and knowledge are moving so fast.”

33:18: “It’s up to us to keep [our microbiome] in a compatible, friendly discussion with the genome we inherited from our parents.” But the health of our microbiome also boils down to our lifestyle. “The way we live will dictate the destiny we have.”

34:54: Commercial break: STEM-Talk is an educational service of the Florida Institute for Human and Machine Cognition, a not-for-profit research lab pioneering ground-breaking technologies aimed at leveraging human cognition, perception, locomotion and resilience.

35:30: Two ingredients of auto-immune disease were once thought to be genes and environmental triggers that create inflammation. The question that no one could explain was: “How can these two worlds physically interact to make this happen?”

38:24: Then they stumbled upon zonulin, a protein modulating the permeability of tight junctures between cells in the digestive tract.

39:20: Now zonulin has been linked to a myriad of auto-immune and GI disease such as Crohn’s Disease, as well as multiple sclerosis, cancer, schizophrenia, and autism.

40:12: Larazotide acetate is a promising peptide that blocks zonulin. It is now in in a phase three clinical trial.

44:40: Zonulin negotiates the interaction with the environment when it’s at the forefront of the gut; it also modulates traffic between body compartments, including the blood brain barrier (BBB).

45:00: German scientists have linked the production of zonulin to more advanced stages of glioma; the more compromised the BBB is, the more zonulin is present.

45:30: The microbiome may have a role in autism, since kids with autism have GI upsets. They are trying to understand what the role of the microbiome is in that. Either the activated immune cells create inflammation in the brain; or the microbiome produces metabolites that have a direct effect on the brain.

46:40: The truth of today is the garbage of tomorrow. Science is refurbished every five years. “You need to put yourself in the discussion all the time,” Fasano says. “If you are not open-minded enough, you will go out of business.”

47:35: Fasano’s grandfather told him, “If you want immediate success, science is not your field.” Another attribute of a scientist is humility: you have to question yourself all the time. “Science is a constellation of failures with very few successes, and we live for those. How bored would we be if every experiment that we did was successful?”

49:38: Dawn relays a personal story about scientists’ dedication: As a post-doc, she had a sign in her office that a mentor had given her, which said: “Brick walls are there for a reason. They make you prove how badly you want something.”

50:06: “Science in Italy is a hobby today,” Fasano says. Italy invests less than three percent of its GDP in science. “There’s no way that Italy can keep apace with countries like the U.S. that consider science an investment. Bright people relocate to unleash their creativity and make a difference.”

51:36: He adds, “Italian science has the resources to be at forefront of the story.”

52:47: Fasano recently opened a research institute in his hometown of Salerno called the European Biomedical Research Institute. It is on the site of the first Western medical school, where the first medical school textbook was written; the first diploma to be a doctor was given; and the first female physician practiced.

55:40: This institute is mainly focused on nutritional health.

56:30: Fasano says his biggest adjustment to living in the U.S. has been lifestyle. “Here people live to work.” And of course, the food. “In the beginning I could not adjust to fast food. I am a strong proponent of slow food. Drive-ins in Italy are inconceivable.”

58:00: What he loves about living in the U.S.: “The sky’s is the limit in terms of realizing your potential.”

59:10: Ken wraps up: “We humans appear to be a kind of super organism. Humans and microbes have developed a co-dependency which affects our wellness, including the expression of our genes.”

59:46: Dawn and Ken sign off.