digestion
The Hidden Beauty of Intestinal Villi
Posted on by Dr. Francis Collins
The human small intestine, though modest in diameter and folded compactly to fit into the abdomen, is anything but small. It measures on average about 20 feet from end to end and plays a big role in the gastrointestinal tract, breaking down food and drink from the stomach to absorb the water and nutrients.
Also anything but small is the total surface area of the organ’s inner lining, where millions of U-shaped folds in the mucosal tissue triple the available space to absorb the water and nutrients that keep our bodies nourished. If these folds, packed with finger-like absorptive cells called villi, were flattened out, they would be the size of a tennis court!
That’s what makes this this microscopic image so interesting. It shows in cross section the symmetrical pattern of the villi (its cells outlined by yellow) that pack these folds. Each cell’s nucleus contains DNA (teal), and the villi themselves are fringed by thousands of tiny bristles, called microvilli (magenta), which are too small to see individually here. Collectively, microvilli make up an absorptive surface, called the brush border, where digested nutrients in the fluid passing through the intestine can enter cells via transport channels.
Amy Engevik, a researcher at the Medical University of South Carolina, Charleston, took this snapshot to show what a healthy intestinal cellular landscape looks like in a young mouse. The Engevik lab studies the dynamic movement of ions, water, and proteins in the intestine—a process that goes wrong in humans born with a rare disorder called microvillus inclusion disease (MVID).
MVID causes chronic gastrointestinal problems in newborn babies, due to defects in a protein that transports various cellular components. Because they cannot properly absorb nutrition from food, these tiny patients require intravenous feeding almost immediately, which carries a high risk for sepsis and intestinal injury.
Engevik and her team study this disease using a mouse model that replicates many of the characteristics of the disorder in humans [1]. Interestingly, when Engevik gets together with her family, she isn’t the only one talking about MVID and villi. Her two sisters, Mindy and Kristen, also study the basic science of gastrointestinal disorders! Instead of sibling rivalry, though, this close alliance has strengthened the quality of her research, says Amy, who is the middle child.
Beyond advancing science and nurturing sisterhood in science, Engevik’s work also captured the fancy of the judges for the Federation of American Societies for Experimental Biology’s annual BioArt Scientific Image and Video Competition. Her image was one of 10 winners announced in December 2020.
Because multiple models are useful for understanding fundamentals of diseases like MVID, Engevik has also developed a large-animal model (pig) that has many features of the human disease [2]. She hopes that her efforts will help to improve our understanding of MVID and other digestive diseases, as well as lead to new, potentially life-saving treatments for babies suffering from MVID.
References:
[1] Loss of MYO5B Leads to reductions in Na+ absorption with maintenance of CFTR-dependent Cl- secretion in enterocytes. Engevik AC, Kaji I, Engevik MA, Meyer AR, Weis VG, Goldstein A, Hess MW, Müller T, Koepsell H, Dudeja PK, Tyska M, Huber LA, Shub MD, Ameen N, Goldenring JR. Gastroenterology. 2018 Dec;155(6):1883-1897.e10.
[2] Editing myosin VB gene to create porcine model of microvillus inclusion disease, with microvillus-lined inclusions and alterations in sodium transporters. Engevik AC, Coutts AW, Kaji I, Rodriguez P, Ongaratto F, Saqui-Salces M, Medida RL, Meyer AR, Kolobova E, Engevik MA, Williams JA, Shub MD, Carlson DF, Melkamu T, Goldenring JR. Gastroenterology. 2020 Jun;158(8):2236-2249.e9.
Links:
Microvillus inclusion disease (Genetic and Rare Diseases Center/NIH)
Digestive Diseases (National Institute of Diabetes and Digestive and Kidney Diseases/NIH)
Amy Engevik (Medical University of South Carolina, Charleston)
Podcast: A Tale of Three Sisters featuring Drs. Mindy, Amy, and Kristen Engevik (The Immunology Podcast, April 29, 2021)
BioArt Scientific Image and Video Competition (Federation of American Societies for Experimental Biology, Bethesda, MD)
NIH Support: National Institute of Diabetes and Digestive and Kidney Diseases
Creative Minds: Giving Bacteria Needles to Fight Intestinal Disease
Posted on by Dr. Francis Collins
Cammie Lesser
For Salmonella and many other disease-causing bacteria that find their way into our bodies, infection begins with a poke. That’s because these bad bugs are equipped with a needle-like protein filament that punctures the outer membrane of human cells and then, like a syringe, injects dozens of toxic proteins that help them replicate.
Cammie Lesser at Massachusetts General Hospital and Harvard Medical School, Cambridge, and her colleagues are now on a mission to bioengineer strains of bacteria that don’t cause disease to make these same syringes, called type III secretion systems. The goal is to use such “good” bacteria to deliver therapeutic molecules, rather than toxins, to human cells. Their first target is the gastrointestinal tract, where they hope to knock out hard-to-beat bacterial infections or to relieve the chronic inflammation that comes with inflammatory bowel disease (IBD).
Creative Minds: Potential Diabetes Lessons from Binge-Eating Snakes
Posted on by Dr. Francis Collins
Stephen Secor/Credit: Secor Lab
Many people would do just about anything to avoid an encounter with a snake. Not Stephen Secor. Growing up in central New York State, Secor was drawn to them. He’d spend hours frolicking through forest and field, flipping rocks and hoping to find one. His animal-loving mother encouraged him to keep looking, and she even let him keep a terrarium full of garter snakes in his bedroom. Their agreement: He must take good care of them—and please make sure they don’t get loose.
As a teen, Secor considered a career as a large-animal veterinarian. But a college zoology course led him right back to his fascination with snakes. Now a professor at the University of Alabama, Tuscaloosa, he’s spent 25 years trying to understand how some snakes, such as the Burmese python shown above, can fast for weeks or even months, and then go on a sudden food binge. Secor’s interest in the feast-or-famine digestive abilities of these snakes has now taken an unexpected turn that he never saw coming: a potential treatment to help people with diabetes.
Creative Minds: The Human Gut Microbiome’s Top 100 Hits
Posted on by Dr. Francis Collins
Michael Fishbach
Microbes that live in dirt often engage in their own deadly turf wars, producing a toxic mix of chemical compounds (also called “small molecules”) that can be a source of new antibiotics. When he started out in science more than a decade ago, Michael Fischbach studied these soil-dwelling microbes to look for genes involved in making these compounds.
Eventually, Fischbach, who is now at the University of California, San Francisco, came to a career-altering realization: maybe he didn’t need to dig in dirt! He hypothesized an even better way to improve human health might be found in the genes of the trillions of microorganisms that dwell in and on our bodies, known collectively as the human microbiome.
Creative Minds: Making a Miniature Colon in the Lab
Posted on by Dr. Francis Collins
Caption: Top down view of gut tissue monolayer grown on an engineered scaffold, which guides the cells into organized crypts structures similar to the conformation of crypts in the human colon. Areas between the circles represent the flat lumenal surface.
Credit: Nancy Allbritton, University of North Carolina, Chapel Hill
When Nancy Allbritton was a child in Marksville, LA, she designed and built her own rabbit hutches. She also once took apart an old TV set to investigate the cathode ray tube inside before turning the wooden frame that housed the TV into a bookcase, which, by the way, she still has. Allbritton’s natural curiosity for how things work later inspired her to earn advanced degrees in medicine, medical engineering, and medical physics, while also honing her skills in cell biology and analytical chemistry.
Now, Allbritton applies her wide-ranging research background to design cutting-edge technologies in her lab at the University of North Carolina, Chapel Hill. In one of her boldest challenges yet, supported by a 2015 NIH Director’s Transformative Research Award, Allbritton and a multidisciplinary team of collaborators have set out to engineer a functional model of a large intestine, or colon, on a microfabricated chip about the size of a dime.
Creative Minds: New Piece in the Crohn’s Disease Puzzle?
Posted on by Dr. Francis Collins
Gwendalyn Randolph
Back in the early 1930s, Burrill Crohn, a gastroenterologist in New York, decided to examine intestinal tissue biopsies from some of his patients who were suffering from severe bowel problems. It turns out that 14 showed signs of severe inflammation and structural damage in the lower part of the small intestine. As Crohn later wrote a medical colleague, “I have discovered, I believe, a new intestinal disease …” [1]
More than eight decades later, the precise cause of this disorder, which is now called Crohn’s disease, remains a mystery. Researchers have uncovered numerous genes, microbes, immunologic abnormalities, and other factors that likely contribute to the condition, estimated to affect hundreds of thousands of Americans and many more worldwide [2]. But none of these discoveries alone appears sufficient to trigger the uncontrolled inflammation and pathology of Crohn’s disease.
Other critical pieces of the Crohn’s puzzle remain to be found, and Gwendalyn Randolph thinks she might have her eyes on one of them. Randolph, an immunologist at Washington University, St. Louis, suspects that Crohn’s disease and other related conditions, collectively called inflammatory bowel disease (IBD), stems from changes in vessels that carry nutrients, immune cells, and possibly microbial components away from the intestinal wall. To pursue this promising lead, Rudolph has received a 2015 NIH Director’s Pioneer Award.
Who Knew? Gut Bacteria Contribute to Malnutrition
Posted on by Dr. Francis Collins
A child suffering from kwashiorkor.
Source: CDC/Phil
Here’s a surprising result from a new NIH-funded study: a poor diet isn’t the only cause of severe malnutrition. It seems that a ‘bad’ assortment of microbes in the intestine can conspire with a nutrient poor diet to promote and perpetuate malnutrition [1].
Most of us don’t spend time thinking about it, but healthy humans harbor about 100 trillion bacteria in our intestines and trillions more in our nose, mouth, skin, and urogenital tracts. And though your initial reaction might be “yuck,” the presence of these microbes is generally a good thing. We’ve evolved with this bacterial community because they provide services—from food digestion to bolstering the immune response—and we give them food and shelter. We call these bacterial sidekicks our ‘microbiome,’ and the latest research, much of it NIH-funded, reveals that these life passengers are critical for good health. You read that right—we need bacteria. The trouble starts when the wrong ones take up residence in our body, or the bacterial demographics shift. Then diseases from eczema and obesity to asthma and heart disease may result. Indeed, we’ve learned that microbes even modulate our sex hormones and influence the risk of autoimmune diseases like type 1 diabetes. [2]
