Highlights from Experimental Biology 2019

BY LUCY MAILING, MD/PHD STUDENT

Two weeks ago, I attended Experimental Biology (EB) in Orlando, Florida, and enjoyed lots of great talks on the gut microbiota, prebiotics, gut barrier function, aging, and more! I finally had a chance to put together some of my highlights from the conference, and I have to say it was by far my favorite EB yet. Read on for some of the latest cutting-edge research in gut health from leaders in the field.

Warning: Some of these are pretty science-dense, but I felt this was the only way to do the research justice without making this three times as long. Feel free to skim the headlines and only read the sections that might interest you, or skip down below for my favorites in Orlando.

1) Antibiotic overuse is leading to a “disappearing microbiota”

Dr. Martin Blaser gave a fascinating talk on Sunday about antibiotics and a changing microbiome. He presented his theory of a disappearing microbiota, highlighting the loss of microbial diversity over successive generations, and with increasing urbanization and development. While antibiotics were one of the greatest discoveries of the 20th century, their overuse, especially during pregnancy and early life, may have long-lasting effects and increase the risk of chronic diseases like diabetes, GERD, asthma, and obesity. Recent estimates suggest that 73 billion antibiotic doses are used worldwide every year, with children receiving an average of 2.7 courses of antibiotics by age two and 10.9 courses by age ten. We are only just beginning to understand the consequences of this widespread overuse and the loss of microbial species that have co-evolved with us over thousands of years.

(Dr. Blaser has written an excellent book on this topic, called “Missing Microbes” which I highly recommend.)

2) Response to prebiotics is highly individualized, but new diagnostic tools may help tailor prebiotic therapy

Dr. David Lawrence from Duke University spoke about how prebiotic fibers shape the gut microbiome. Several research groups have shown that prebiotic responses are highly individualized. His lab has developed a simple assay where a human stool sample can be homogenized, filtered, and combined with 24 different prebiotic solutions on a 24-well plate. They can then measure downstream metabolites, including how much butyrate is produced from each prebiotic. The hope is that these could eventually be used as diagnostic tools to tailor prebiotic therapy to each individual’s gut microbiome! Ongoing human clinical studies are examining how well the prebiotic assay results align with the actual response in an individual.

3) The gut microbiota regulates susceptibility to atherosclerosis

Dr. Federico Rey from the University of Wisconsin-Madison shared some of his lab’s most recent work on the connection between the gut microbiota and atherosclerosis. Using their unique “core communities” model system, they found that Roseburia intestinalis, a key butyrate-producing microbe in the human gut, combined with a diet high in fiber, can inhibit the development of atherosclerosis in genetically susceptible mouse strains. The reduction in atherosclerotic plaque formation may be due to improved barrier function and a reduction in systemic inflammation.

4) The short-chain fatty acid acetate is implicated in obesity – at least in mice

Dr. Rachel Perry from Yale University presented some of her research on the short-chain fatty acid (SCFA) acetate. An intriguing body of work published by her lab in 2016 has shown that chronic acetate infusion increases weight gain in mice by increasing parasympathetic activity in the nervous system. However, I am not convinced that the same holds true in humans, and have written about this before. Human receptors for acetate respond very differently than mouse receptors for acetate, and experiments involving acetate enemas or vinegar consumption have largely shown positive metabolic effects. When pressed on the issue, Dr. Perry acknowledged that are seeing less of an effect in humans than in rodents, and more clinical research is needed.

5) Microbial communities on the skin explain the locations of different skin conditions

Dr. Julie Segre of the National Human Genome Research Institute gave an interesting talk on the bacteria, fungi, and viruses that make up the human skin microbiome. In recent years, she and her research team have particularly focused on surveying areas of dermatological interest for different skin diseases. If you’ve ever wondered why eczema tends to show up on your inner elbows, but acne shows up on your face, it turns out that this can largely be explained by differences in the local environment (moist, oily, dry, etc.) and the different microbes they can support. Skin microbial communities are surprisingly stable over time, but certain opportunistic pathogens may drive changes that are associated with flares. For instance, Staphylococcus spp. has been shown to drive a reduction in skin microbial diversity that is associated with flares of atopic dermatitis.

6) Many molecules and pathways influence gut barrier function and intestinal permeability

Over the course of the conference, I also heard many talks and visited many posters by researchers that have identified key components in regulating gut barrier function. Dr. Jian-Ying Wang of the University of Maryland presented some particularly interesting data suggesting that certain long noncoding RNAs can regulate gut barrier function. Only about four percent of the human genome codes for proteins, with the remainder transcribed into a number of noncoding RNAs that appear to have regulatory functions. Dr. Wang’s lab has identified two long noncoding RNAs (SPRY4-IT1 and uc.173) that influence epithelial barrier function and mucosal renewal. The hope is that eventually these may be used as therapeutics to help improve gut barrier function in a wide range of chronic diseases.

7) Akkermansia muciniphila and Lactobacillus facilitate epithelial wound healing

On the final day of the conference, Dr. Andrew Neish from Emory University presented some fascinating research on the microbiota and wound repair in the gut mucosa. The gut epithelium is the most dynamically renewing tissue in mammals, and studies in germ free mice have shown that the gut microbiota contributes to repair responses in the gut. Dr. Neish’s lab has found that there seems to be a enrichment of Akkermansia muciniphila, a bacterium that is known to colonize the gut mucus layer, and Lactobacillus spp. in epithelial wounds. These microbes stimulate the production of reactive oxygen species in the local microenvironment, activating signaling pathways that induce stem cell proliferation and enhance epithelial wound healing.

8) The gut microbiota mediates salt sensitive hypertension and autoimmunity

Dr. Dominik Mueller from MDC Berlin presented some fascinating data that suggests that the gut microbiota may mediate salt sensitivity in hypertension and autoimmunity. In a recent publication, Dr. Mueller and colleagues showed that feeding mice a high-salt diet reduced the abundance of Lactobacillus murinus, increased IL-17 cells in the small intestine, colon, and spleen, and increased blood pressure and symptoms of multiple sclerosis in two different animal models. Treating the mice with L. murinus reduced IL-17 cells and partially ameliorated the cardiovascular and autoimmune phenotypes. Diving deeper into the mechanisms, they found that L. murinus produces an indole metabolite that inhibits Th17 cells and reduces inflammation. L. murinus is not native to the human gut microbiota, but in a pilot clinical trial, giving human subjects an extra six grams of salt (about 1 tsp) per day for two weeks caused depletion of several different Lactobacillus species in those who were positive for these populations at baseline. The team next plans to perform a randomized, placebo-controlled clinical study of Lactobacillus spp. as a probiotic supplement in individuals with stage I hypertension.

9) The flavonoid fisetin suppresses cellular senescence to extend lifespan

Dr. Laura Niedemhofer from the University of Minnesota spoke about the evidence that supports DNA damage as a driver of cellular senescence and aging. Nuclear DNA damage that accumulates with age triggers mitochondrial abnormalities, oxidative stress, and damage, leading cells to stop dividing, or become senescent. Senescent cells secrete many damaging molecules, including inflammatory cytokines, and are a major target of interest for anti-aging therapies. Dr. Niedemhofer’s lab has screened for a variety of compounds that are senomorphic, meaning that they modify the inflammatory or secretory phenotype of senescent cells, or senolytic, meaning that they actually kill senescent cells. Of particular interest to me was that the flavonoid fisetin was found to be a particularly potent senolytic agent. In mice, a diet with 500mg/kg fisetin, even started late in life, can improve physical function in old age and extend lifespan!

10) Butyrate drives hypoxia in the gut, promoting mucosal homeostasis

Dr. Sean Colgan from UC Denver presented an interesting overview of microbial-derived mediators influencing mucosal inflammation. It is well established that the short-chain fatty acid butyrate is the preferred energy source for colonic epithelial cells. When butyrate is present, glucose utilization is inhibited, cellular respiration occurs using oxygen inside mitochondria, and the gut mucosa is maintained in a state of “physiologic hypoxia”. A transcription factor called hypoxia-inducible factor (HIF) senses this low oxygen environment and coordinates protection of the intestinal epithelium. However, if butyrate production is low, gut epithelial cells switch to anaerobic fermentation, diminishing mucosal hypoxia and resulting in impaired barrier function. In the near future, I will be devoting an entire blog article to the oxygen-gut dysbiosis-gut barrier connection.

My travel favorites

And for those who might be traveling to Florida anytime soon, here were my favorite restaurants, health food stores, and things to do around Orlando!

Near Cocoa Beach:

Sunseed Natural Foods Co-op: a great little health food store in Cape Canaveral where we picked up some snacks and toxin-free sunscreen before heading to the beach!

Lori Wilson Beach Park: this place was recommended by our Airbnb host, and did not disappoint. We had a great time swimming and relaxing here the day before the conference!

Brasas Grill: our first experience at a Brazilian steakhouse, and it was incredibly delicious. This place is located on Merritt Island, not too far from Cocoa Village.

In Orlando:

Taste of Peru: a wonderful Peruvian restaurant where we tried “Churrasco a lo pobre” and “Pisco sour” for the first time.

Taverna Opa Orlando: a fantastic Greek restaurant near the conference center. I loved their traditional greek salad with salmon and feta cheese.

Pirate’s Cove Adventure Golf: we largely avoided the touristy stuff along International Drive, but this putt-putt golf course was pretty spectacular.

Hopdoddy Burger Bar: definitely not the healthiest place, but their grass-fed burgers are amazing! We went here with a few docs from Mayo Clinic that I met at the conference.

That’s all for now! Be sure to let me know what you thought of this latest research in the comments and subscribe to my newsletter to be notified of new posts. I’ll continue to write these conference summaries as long as you find them useful!

Support more articles like this:
Become a patron

The Best of DDW 2019

The Best of DDW 2019 BY LUCY MAILING, MD/PHD STUDENT A few weeks ago, I had the opportunity to attend Digestive Disease Week in San Diego, California! DDW [...]

Highlights from Experimental Biology 2019

BY LUCY MAILING, MD/PHD STUDENT

Two weeks ago, I attended Experimental Biology (EB) in Orlando, Florida, and enjoyed lots of great talks on the gut microbiota, prebiotics, gut barrier function, aging, and more! I finally had a chance to put together some of my highlights from the conference, and I have to say it was by far my favorite EB yet. Read on for some of the latest cutting-edge research in gut health from leaders in the field.

Warning: Some of these are pretty science-dense, but I felt this was the only way to do the research justice without making this three times as long. Feel free to skim the headlines and only read the sections that might interest you, or skip down below for my favorites in Orlando.

Dr. Martin Blaser gave a fascinating talk on Sunday about antibiotics and a changing microbiome. He presented his theory of a disappearing microbiota, highlighting the loss of microbial diversity over successive generations, and with increasing urbanization and development. While antibiotics were one of the greatest discoveries of the 20th century, their overuse, especially during pregnancy and early life, may have long-lasting effects and increase the risk of chronic diseases like diabetes, GERD, asthma, and obesity. Recent estimates suggest that 73 billion antibiotic doses are used worldwide every year, with children receiving an average of 2.7 courses of antibiotics by age two and 10.9 courses by age ten. We are only just beginning to understand the consequences of this widespread overuse and the loss of microbial species that have co-evolved with us over thousands of years.

(Dr. Blaser has written an excellent book on this topic, called “Missing Microbes” which I highly recommend.)

Dr. David Lawrence from Duke University spoke about how prebiotic fibers shape the gut microbiome. Several research groups have shown that prebiotic responses are highly individualized. His lab has developed a simple assay where a human stool sample can be homogenized, filtered, and combined with 24 different prebiotic solutions on a 24-well plate. They can then measure downstream metabolites, including how much butyrate is produced from each prebiotic. The hope is that these could eventually be used as diagnostic tools to tailor prebiotic therapy to each individual’s gut microbiome! Ongoing human clinical studies are examining how well the prebiotic assay results align with the actual response in an individual.
Dr. Federico Rey from the University of Wisconsin-Madison shared some of his lab’s most recent work on the connection between the gut microbiota and atherosclerosis. Using their unique “core communities” model system, they found that Roseburia intestinalis, a key butyrate-producing microbe in the human gut, combined with a diet high in fiber, can inhibit the development of atherosclerosis in genetically susceptible mouse strains. The reduction in atherosclerotic plaque formation may be due to improved barrier function and a reduction in systemic inflammation.
Dr. Rachel Perry from Yale University presented some of her research on the short-chain fatty acid (SCFA) acetate. An intriguing body of work published by her lab in 2016 has shown that chronic acetate infusion increases weight gain in mice by increasing parasympathetic activity in the nervous system. However, I am not convinced that the same holds true in humans, and have written about this before. Human receptors for acetate respond very differently than mouse receptors for acetate, and experiments involving acetate enemas or vinegar consumption have largely shown positive metabolic effects. When pressed on the issue, Dr. Perry acknowledged that are seeing less of an effect in humans than in rodents, and more clinical research is needed.
Dr. Julie Segre of the National Human Genome Research Institute gave an interesting talk on the bacteria, fungi, and viruses that make up the human skin microbiome. In recent years, she and her research team have particularly focused on surveying areas of dermatological interest for different skin diseases. If you’ve ever wondered why eczema tends to show up on your inner elbows, but acne shows up on your face, it turns out that this can largely be explained by differences in the local environment (moist, oily, dry, etc.) and the different microbes they can support. Skin microbial communities are surprisingly stable over time, but certain opportunistic pathogens may drive changes that are associated with flares. For instance, Staphylococcus spp. has been shown to drive a reduction in skin microbial diversity that is associated with flares of atopic dermatitis.
Over the course of the conference, I also heard many talks and visited many posters by researchers that have identified key components in regulating gut barrier function. Dr. Jian-Ying Wang of the University of Maryland presented some particularly interesting data suggesting that certain long noncoding RNAs can regulate gut barrier function. Only about four percent of the human genome codes for proteins, with the remainder transcribed into a number of noncoding RNAs that appear to have regulatory functions. Dr. Wang’s lab has identified two long noncoding RNAs (SPRY4-IT1 and uc.173) that influence epithelial barrier function and mucosal renewal. The hope is that eventually these may be used as therapeutics to help improve gut barrier function in a wide range of chronic diseases.
On the final day of the conference, Dr. Andrew Neish from Emory University presented some fascinating research on the microbiota and wound repair in the gut mucosa. The gut epithelium is the most dynamically renewing tissue in mammals, and studies in germ free mice have shown that the gut microbiota contributes to repair responses in the gut. Dr. Neish’s lab has found that there seems to be a enrichment of Akkermansia muciniphila, a bacterium that is known to colonize the gut mucus layer, and Lactobacillus spp. in epithelial wounds. These microbes stimulate the production of reactive oxygen species in the local microenvironment, activating signaling pathways that induce stem cell proliferation and enhance epithelial wound healing.
Dr. Dominik Mueller from MDC Berlin presented some fascinating data that suggests that the gut microbiota may mediate salt sensitivity in hypertension and autoimmunity. In a recent publication, Dr. Mueller and colleagues showed that feeding mice a high-salt diet reduced the abundance of Lactobacillus murinus, increased IL-17 cells in the small intestine, colon, and spleen, and increased blood pressure and symptoms of multiple sclerosis in two different animal models. Treating the mice with L. murinus reduced IL-17 cells and partially ameliorated the cardiovascular and autoimmune phenotypes. Diving deeper into the mechanisms, they found that L. murinus produces an indole metabolite that inhibits Th17 cells and reduces inflammation. L. murinus is not native to the human gut microbiota, but in a pilot clinical trial, giving human subjects an extra six grams of salt (about 1 tsp) per day for two weeks caused depletion of several different Lactobacillus species in those who were positive for these populations at baseline. The team next plans to perform a randomized, placebo-controlled clinical study of Lactobacillus spp. as a probiotic supplement in individuals with stage I hypertension.
Dr. Laura Niedemhofer from the University of Minnesota spoke about the evidence that supports DNA damage as a driver of cellular senescence and aging. Nuclear DNA damage that accumulates with age triggers mitochondrial abnormalities, oxidative stress, and damage, leading cells to stop dividing, or become senescent. Senescent cells secrete many damaging molecules, including inflammatory cytokines, and are a major target of interest for anti-aging therapies. Dr. Niedemhofer’s lab has screened for a variety of compounds that are senomorphic, meaning that they modify the inflammatory or secretory phenotype of senescent cells, or senolytic, meaning that they actually kill senescent cells. Of particular interest to me was that the flavonoid fisetin was found to be a particularly potent senolytic agent. In mice, a diet with 500mg/kg fisetin, even started late in life, can improve physical function in old age and extend lifespan!
Dr. Sean Colgan from UC Denver presented an interesting overview of microbial-derived mediators influencing mucosal inflammation. It is well established that the short-chain fatty acid butyrate is the preferred energy source for colonic epithelial cells. When butyrate is present, glucose utilization is inhibited, cellular respiration occurs using oxygen inside mitochondria, and the gut mucosa is maintained in a state of “physiologic hypoxia”. A transcription factor called hypoxia-inducible factor (HIF) senses this low oxygen environment and coordinates protection of the intestinal epithelium. However, if butyrate production is low, gut epithelial cells switch to anaerobic fermentation, diminishing mucosal hypoxia and resulting in impaired barrier function. In the near future, I will be devoting an entire blog article to the oxygen-gut dysbiosis-gut barrier connection.
And for those who might be traveling to Florida anytime soon, here were my favorite restaurants, health food stores, and things to do around Orlando!

Near Cocoa Beach:

Sunseed Natural Foods Co-op: a great little health food store in Cape Canaveral where we picked up some snacks and toxin-free sunscreen before heading to the beach!

Lori Wilson Beach Park: this place was recommended by our Airbnb host, and did not disappoint. We had a great time swimming and relaxing here the day before the conference!

Brasas Grill: our first experience at a Brazilian steakhouse, and it was incredibly delicious. This place is located on Merritt Island, not too far from Cocoa Village.

In Orlando:

Taste of Peru: a wonderful Peruvian restaurant where we tried “Churrasco a lo pobre” and “Pisco sour” for the first time.

Taverna Opa Orlando: a fantastic Greek restaurant near the conference center. I loved their traditional greek salad with salmon and feta cheese.

Pirate’s Cove Adventure Golf: we largely avoided the touristy stuff along International Drive, but this putt-putt golf course was pretty spectacular.

Hopdoddy Burger Bar: definitely not the healthiest place, but their grass-fed burgers are amazing! We went here with a few docs from Mayo Clinic that I met at the conference.

That’s all for now! Be sure to let me know what you thought of this latest research in the comments and subscribe to my newsletter to be notified of new posts. I’ll continue to write these conference summaries as long as you find them useful!

Support more articles like this:
Become a patron

The Best of DDW 2019

The Best of DDW 2019 BY LUCY MAILING, MD/PHD STUDENT A few weeks ago, I had the opportunity to attend Digestive Disease Week in San Diego, California! DDW [...]