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Tag: lemurs

Lemur Gut Isn’t One Ecosystem, It’s Many

Lemurs like Ferdinand are leaf-eating machines, says Duke microbiome researcher Lydia Greene. Credit: Lydia Greene

DURHAM, N.C. — A jungle. A rainforest. A wetland. A wilderness. Researchers have used various metaphors to describe the complex, interconnected community of microbes (most of them bacteria) living inside your body, and all over it too.

If you were to count up all the trillions of cells inside and out, we are more bacteria than human. Fortunately, perhaps, the microbes that make a cozy home inside your nose, or clinging to your teeth, aren’t the same ones that are living behind your ear or busily multiplying in your belly button.

The same is true for our distant primate cousins the lemurs, particularly in their guts, say researchers Lydia Greene and Erin McKenney in a new study.

Lemurs rely on gut microbes to digest their leafy diets, explains Greene, a research scientist at the Duke Lemur Center. Microbes in lemurs’ GI tracts help ferment plant fiber, detoxify plant chemical defenses, and synthesize vitamins and nutrients that lemurs can’t make for themselves. Our own gut bugs do many of the same things for us.

Greene and McKenney study how lemur gut bacteria are shaped by what lemurs eat, how they evolved and the complexity of the route microbes travel through the body. They hope to better understand how these microorganisms keep lemurs healthy, or — when they’re out of balance — make them sick.

Researchers who do this kind of work spend a lot of time collecting poop. For good reasons, says McKenney, an assistant professor at North Carolina State University. Scientists can learn about lemurs by what they leave behind, and poop can be collected repeatedly without harming the animals. But for this study the team tried something different, made possible by a one-of-a-kind biobank:

When an animal dies at the Duke Lemur Center, veterinary staff determine the cause of death, and blood and tissue samples that might be important for research or education are collected and preserved.

Today, the collection holds thousands of samples, collected over decades from more than two dozen species of rare and endangered primates, which the center stores in super cold freezers in their headquarters in North Carolina. It’s a frozen ark maintained at up to minus 80 degrees Celsius, with redundant backup power.

In the event that any one of these species goes extinct, and the last living parts of them are gone, future generations will still be able to study the genetic and other information they left behind.

Using this bank, the team sampled several sites in the bowels of 52 deceased lemurs, including dwarf lemurs, aye-ayes, ruffed lemurs, bamboo lemurs, brown lemurs, ring-tailed lemurs and sifakas.

A trip through a lemur’s GI tract is a journey through a varied landscape. The long, twisting route from the stomach through the small intestine to the colon serves numerous functions, filtering, digesting, absorbing, detoxifying, fermenting.

Not all lemur guts work the same: Fruit-eaters, like ruffed lemurs, generally have short, simple guts. If you stretched them out, they’d be five times their body length — not much shorter than ours, relative to body size. Leaf-eaters like sifakas have more complex GI tracts with relatively longer colons and a leaf-fermentation pouch called a cecum. Their guts are the lemur champions — up to 16 times body length.

Having whole lemurs to study instead of just poo enabled the researchers to sample different regions of the gut to figure out what kinds of microbes were present in each spot. They used genetic sequencing technology to identify microbes and compare their relative abundance in different sites.

Sampling along the digestive tract, they found that different spots along this long, twisting pathway have their own communities of bacteria doing different kinds of jobs. The complex ecosystem lurking in a lemur’s small intestine, for example, isn’t the same as the microbial menagerie setting up camp in their colon.

Levels of biodiversity varied too. The stomach supports less microbial life because fewer species can tolerate its acidic digestive juices. But if the upper regions of the gut are a garden, the lower regions are more like a tropical rainforest. About two dozen types of bacteria were more abundant in the cecum and colon than elsewhere. Lemurs with relatively longer lower guts host the richest microbiomes, to better ferment high-fiber foods.

“We probably couldn’t have detected these relationships without such an extensive comparative dataset,” McKenney said.

“This kind of lemur research can really only be done at the Duke Lemur Center,” Greene said.

Rodelinda, a Coquerel’s sifaka lemur, munches on leaves at the Duke Lemur Center. Credit: Lydia Greene.

This research was supported by the National Science Foundation (DBI PRFB 1906416) and by a Duke Lemur Center Director’s fund.

CITATION: “Gut Site and Gut Morphology Predict Microbiome Structure and Function in Ecologically Diverse Lemurs,” Lydia K. Greene, Erin A. McKenney, William Gasper, Claudia Wrampelmeier, Shivdeep Hayer, Erin E. Ehmke, & Jonathan B. Clayton. Microbial Ecology, May 14, 2022. DOI: 10.1007/s00248-022-02034-4

When the gut’s internal ecosystem goes awry, could an ancient if gross-sounding treatment make it right?

Lemur researchers make a case for fecal transplants to reduce the side effects of antibiotics. Photo by David Haring, Duke Lemur Center.

Dr. Cathy Williams knew something wasn’t right. The veterinarian had felt off for weeks after her 2014 trip to Madagascar.

At first she just felt bloated and uncomfortable and wasn’t interested in eating much. But eventually she developed a fever and chills that sent her to the emergency room.

When tested, doctors found that what she had wasn’t just a stomach bug. She was suffering from an infection of Clostridium difficile, a germ that causes severe diarrhea and abdominal pain and can quickly become life-threatening if not treated promptly.

“It was horrible,” Williams said.

The condition is often triggered when antibiotics disrupt the normal balance of bacteria that inhabit the gut, allowing “bad” bacteria such as C. difficile to multiply unchecked and wreak havoc on the intestines.

To get her infection under control, Williams asked her doctors if they could try an approach she and other veterinarians had used for decades to treat lemurs with digestive problems at the Duke Lemur Center. The procedure, known as a fecal microbiota transplant, involves taking stool from a healthy donor and administering it to the patient to add back “good” microbes and reset the gut.

At the time it was considered too experimental for clinical use in human cases like Williams’. She was prescribed the standard treatment and was sent home from the hospital, though she wouldn’t feel well enough to go back to work for another month. But now new research in lemurs is confirming what Williams and others long suspected: that this ancient if gross-sounding treatment can help an off-kilter gut microbiome get back to normal.

In a recent study in the journal Animal Microbiome, a research team led by Duke professor Christine Drea, former PhD student Sally Bornbusch and colleagues looked at the gut microbiomes of 11 healthy ring-tailed lemurs over a four-month period after receiving a seven-day course of the broad-spectrum antibiotic amoxicillin.

The lemurs were split into two experimental groups. One was a wait-and-see group, with continued follow-up but no further treatment after the antibiotics. The other group was given a slurry of their own feces, collected prior to antibiotic treatment and then mixed with saline and fed back to the same animal after their course of antibiotics was over.

“It sounds crazy,” Williams said. But she has used a similar procedure since the 1990s to treat illnesses in Coquerel’s sifaka lemurs, whose infants are known to eat their mother’s poop during weaning — presumably to get the microbes they’ll need to transition to solid food.

A baby Coquerel’s sifaka tries some of her first solid foods. Photo by David Haring.

Drea, Bornbusch and team used genetic sequencing techniques to track changes in the lemurs’ gut microbiome before, during and after treatment.

As expected, even a single course of antibiotics caused the numbers of microbes in their guts to plunge compared with controls, briefly wiping out species diversity in both experimental groups before returning to baseline.

“Antibiotics had dramatic effects, even in healthy animals,” Drea said.

But in terms of which types of bacteria bounced back and when, the patterns of recovery in the two groups were different. Lemurs that received the “poop soup” treatment started to stabilize and return to their pre-antibiotic microbiome within about two weeks. In contrast, the bacterial composition in the wait-and-see group continued to fluctuate, and still hadn’t quite returned to normal even after four months of observation.

This kind of therapy isn’t new. Reports of using fecal transplants to treat people suffering from food poisoning or diarrhea date back as far as fourth century China. The evidence for its effectiveness in captive settings has Bornbusch advocating for freezing stool at Smithsonian’s National Zoo, where she is now a postdoctoral fellow.

“If we can bank feces from animals when they’re healthy, that can be a huge benefit down the road,” Bornbusch said. “It can help the animals get better, faster.”

And now if any of her lemur patients were to get sick with C. difficile like she did, Williams said, “I would absolutely go with a fecal microbiota transplant.”

“People are put off by it,” Drea said, “But the disgust for this approach might actually have been holding up a fairly cheap and useful cure.”

Ring-tailed lemurs at the Duke Lemur Center in North Carolina. Photo by David Haring, Duke Lemur Center

This research was supported by the National Science Foundation (BCS 1749465), the Duke Lemur Center Director’s Fund, and the Duke Microbiome Center.

CITATION: “Antibiotics and Fecal Transfaunation Differentially Affect Microbiota Recovery, Associations, and Antibiotic Resistance in Lemur Guts,” Sally L. Bornbusch, Rachel L. Harris, Nicholas M. Grebe, Kimberly Roche, Kristin Dimac-Stohl, Christine M. Drea. Animal Microbiome, Oct. 1, 2021. DOI: 10.1186/s42523-021-00126-z.

By Robin Ann Smith

Scents Are Key to Lemur Nightlife

LEMUR SUPERPOWER #457:  Some lemurs can safely digest cyanide in amounts sufficient to kill an elephant. Others can enter hibernation-like states to survive periods when food and water are in short supply. To add to their list of superpowers, lemurs also have especially keen powers of scent.

Buried in the nose of Fuggles the mouse lemur are specialized pheromone receptors that help her distinguish friend from foe in the dark of night, when mouse lemurs are active.

By Robin Ann Smith

If you could pick one superpower, consider taking inspiration from lemurs. Some lemurs can safely digest cyanide in amounts that would kill an elephant. Others can enter hibernation-like states to survive periods when food and water are in short supply. Still others have keen powers of scent, with the ability to find mates and avoid enemies in the darkness by smell alone.

Research by biologist and Duke Lemur Center director Anne Yoder suggests that the molecular machinery for sniffing out pheromones — much of which has gone defunct in humans and many other primates — is still alive and well in lemurs and lorises, our distant primate cousins.

Lemurs use scents to mark the boundaries of their territories, distinguish males from females and figure out whether another animal is friend or foe. When a lemur gets a whiff of another animal, specialized pheromone receptors in the lining of the nose transmit the information to the brain, triggering instinctive urges like mating, defense and avoiding predators.

The receptors are proteins encoded by a family of genes called V1Rs. First identified in rats in the mid-1990s, V1R genes are found in animals ranging from lampreys to humans. But the proportion of these pheromone-detection genes that actually functions varies greatly from one species to the next, Yoder said last week in a roundtable discussion hosted by Duke’s Science & Society program.

Randy the ring-tailed lemur scent-marks his territory. Photo by David Haring.

Randy the ring-tailed lemur scent-marks his territory. Photo by David Haring.

Studies suggest that as much as 90% to 100% of the pheromone-detection genes in humans consist of disabled pieces of DNA, called pseudogenes.

“Our pheromone-detection genes are so boring — we don’t have many of them, and almost all of them are broken,” Yoder said.

But in lemurs and lorises — whose ancestors split off from the rest of the primate family tree more than 60 million years ago — the proportion of pheromone-detection genes that is still intact is much higher.

In a study published this year, Yoder and colleagues analyzed the DNA of 19 species and subspecies of lemurs and lorises, looking for subtle differences in their V1R genes. They found that one group — the mouse lemurs — has the highest proportion of intact V1R sequences of any mammal yet studied.

To find out which genes are linked to which scents, Yoder and her colleagues plan to take DNA sequences from pheromone-detecting genes in lemurs, insert them into mice, and expose the mice to different scents to see how they respond.

An ability to sniff out the right mates — and avoid being seduced by the wrong suitors — may have served as a mating barrier that allowed lemur species to diverge after arriving in their island home of Madagascar, helping to explain how the more than 70 living species of lemurs came to be, Yoder says.

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