Creative Minds: The Human Gut Microbiome’s Top 100 Hits

Michael Fischbach

Michael Fischbach

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.

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Simplifying HIV Treatment: A Surprising New Lead

CD4+ cells in the gut

Caption: PET/CT imaging reveals a surprisingly high concentration (yellow, light green) of key immune cells called CD4 T cells in the colon (left) of an SIV-infected animal that received antibody infusions along with antiviral treatment. Fewer immune cells were found in the small intestine (right), while the liver (lower left) shows a high level of non-specific signal (orange).
Credit: Byrareddy et al., Science (2016).

The surprising results of an animal study are raising hopes for a far simpler treatment regimen for people infected with the AIDS-causing human immunodeficiency virus (HIV). Currently, HIV-infected individuals can live a near normal life span if, every day, they take a complex combination of drugs called antiretroviral therapy (ART). The bad news is if they stop ART, the small amounts of HIV that still lurk in their bodies can bounce back and infect key immune cells, called CD4 T cells, resulting in life-threatening suppression of their immune systems.

Now, a study of rhesus macaques infected with a close relative of HIV, the simian immunodeficiency virus (SIV), suggests there might be a new therapeutic option that works by a mechanism that has researchers both excited and baffled [1]. By teaming ART with a designer antibody used to treat people with severe bowel disease, NIH-funded researchers report that they have been able to keep SIV in check in macaques for at least two years after ART is stopped. More research is needed to figure out exactly how the new strategy works, and whether it would also work for humans infected with HIV. However, the findings suggest there may be a way to achieve lasting remission from HIV without the risks, costs, and inconvenience associated with a daily regimen of drugs.

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Creative Minds: Making a Miniature Colon in the Lab

Gut on a Chip

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.

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Nanojuice: Getting a Real-Time View of GI Motility

Nanojuice as it passes through the gut of the mouse

Caption: A real-time image of nanojuice as it passes through a mouse’s small intestine. A laser causes particles in the nanojuice to vibrate, creating vibrations picked up by an ultrasound detector that are then used to generate a black-and-white image. Rainbow colors are added afterward to reflect the depth of the intestine within the mouse’s abdomen: blue is closest to the surface and red is deepest.
Credit: Jonathan Lovell, University at Buffalo

For those of you who love to try new juices, you’ve probably checked out acai, goji berry, and maybe even cold-pressed kale. But have you heard of nanojuice? While it’s not a new kind of health food, this scientific invention may someday help to improve human health through its power to visualize the action of the gastrointestinal (GI) tract in real-time.

It’s true that doctors already have many imaging tools at their disposal to examine various parts of the GI tract—all the way from throat to colon. These include invasive techniques, such as upper endoscopy and colonoscopy; as well as non-invasive approaches, such as ultrasound, magnetic resonance imaging, and X-ray procedures that may or may not involve swallowing a chalky liquid containing barium or other materials that are radio-opaque. There’s even a wireless capsule that can shoot videos as it travels all the way through the GI tract. None of these techniques, however, provides a non-invasive, real-time view of the wave-like muscle contractions that move food through the gut—a crucial process called peristalsis.

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