A Beeautiful Gut Feeling

“Look,” says Tobin Hammer, using a white-light headlamp to illuminate a colony of some 250 bumblebees in the basement of Steinhaus Hall. “They’re a bit agitated.”

He had just opened a box where the bees live in a walk-in “rearing chamber” kept at 80 degrees Fahrenheit and bathed in red lights – which keep the bees calm, since that hue hampers their vision.

It’s what the eyes can’t see that’s the focus of one of Hammer’s main research projects.

The UC Irvine assistant professor of ecology and evolutionary biology, along with a few fellow bug nerds who are his undergraduate, graduate and postdoctoral researchers, is studying the microbiome of the favorite, fuzzy and charismatic American bee.

As it turns out, the scores of bacteria, fungi, viruses and other microorganisms living in the guts of bumblebees have surprising parallels with those of humans.

Exploring them may lead to better gastrointestinal and brain health in humans, as experts like Hammer see how tinkering with the bees’ microbiomes affects their health. And such research also could be critical to bumblebees, because their populations are under threat from climate change, loss of habitat and other factors.

The hum of the bees in the rearing chamber is quieter than the sound bumblebees make as they use vibrations to engage in “buzz pollination,” which is needed by some plants, such as blueberries, to produce fruit. Poppies are a favorite of bumblebees, which are among the most important pollinators of not just blueberry, but cranberry, tomato, eggplant, sweet pepper and other key agricultural crops.

Hammer, back in his third-floor lab, says bumblebees are ideal for laboratory research because their colonies, relatively small at 200 to 300, are easily contained. Honeybee colonies, in comparison, can total in the tens of thousands. Also, honeybees swarm and roam over large areas. Bumblebees don’t do either, confining themselves to patches of flowers and plants. “Bumblebees are our lab rats,” Hammer says above the murmur of an ultra-low freezer, where cryopreserved bacterial cultures and specimens for DNA sequencing are stored.

His lab is filled with bee memorabilia such as books (OMFG, Bees! is a gift from his father), illustrations and jigsaw puzzles. As for bee puns, which are difficult to avoid, Hammer has heard them all. “I try not to encourage them,” he says with the look of someone who has been told too many dad jokes.

Growing up in the Bay Area’s Redwood City, Hammer has had a lifelong fascination with animals and bugs. Zoos and nature documentaries were among his favorite pastimes. For the last 14 years, bees have been his focus. He began studying them as an undergraduate at UC San Diego.

“We see some parallels between humans and bumblebees in terms of how microbes are transmitted. In both cases, we believe social lifestyle is important to maintaining the bacteria from generation to generation.”

– Tobin Hammer

Shortly thereafter, Hammer developed a parallel fascination with microbes, initially investigating deep-sea sediments and saltwater lakes.

His UC Irvine lab – which opened two years ago when he arrived from the University of Texas at Austin, where he had been a postdoc – is now one of the largest in the country devoted to researching the microbiomes of bumblebees, which are native to the United States, unlike the ubiquitous and much-studied honeybees, which come from Europe and Asia.

‘The Invisible Organ’

Researchers have been studying microbes in the human GI tract for decades, and DNA sequencing technology has accelerated discovery dramatically over the last 15 years.

Why all the focus? Gut microbes contribute to human health and prevent disease, and the hope is that, in the future, people will be able to take customized probiotics for certain health issues.

“Researchers, when describing the importance of microbiomes, like to call them ‘the invisible human organ’ or ‘the organ we didn’t know we have,’” Hammer says. “We’re discovering how essential gut microbes are to the functioning of our body.”

Some GI diseases, allergies and autoimmune disorders are blamed on poor or malfunctioning gut microbiomes, and an emerging field of research links gut microbiomes to behavior.

“Some gut bacteria can produce neurotransmitters, which means they can alter the function of the brain and thus mood, stress levels and other things,” Hammer explains. This, in fact, is the gist of a lab project of his that involves probing the effects of microbes on learning and memory in bees.

The species of yellow-faced bumblebee that’s the focus of Hammer’s microbiome study is Bombus vosnesenskii, the most abundant bumblebee on the West Coast – found in natural, suburban and urban landscapes from British Columbia to Baja California. The worker bees of this species are active April through November.

Like humans, bumblebees live in family groups and exhibit complex social structures and behaviors. Unlike humans, bumblebee behavior and microbiomes can be experimentally manipulated in the lab.

That’s where Hammer’s rearing chamber comes in. The two colonies in separate boxes in the chamber were purchased by his lab from companies that mostly sell them to farms to pollinate crops. They are the species Bombus impatiens, not native to Southern California but closely related to Bombus vosnesenskii.

Hammer and his researchers study Bombus vosnesenskii in the field and Bombus impatiens in the lab. They pluck untainted cocoons from the lab colonies and introduce pathogens and genetically engineered strains of bacteria to study the baby bees’ microbiomes and how they affect behavior.

First, team members use glue to attach printed QR codes to the backs of the bees and place about 50 of them in coffeemaker-sized contraptions called bee surveillance chambers. A computer records videos of the bees’ interactions that are saved on a thumb drive for later analysis.

“We see some parallels between humans and bumblebees in terms of how microbes are transmitted,” Hammer says. “In both cases, we believe social lifestyle is important to maintaining the bacteria from generation to generation.”

The gut structures of humans and bumblebees are roughly analogous, he says. The bee has a foregut; we have an esophagus. The bee midgut is comparable to our small intestines, and the hindgut of a bee equates to our large intestines. In both bees and humans, the bacteria and millions of other gut microbes live almost entirely in the hindgut – past the region where humans and bees absorb most nutrients.

“The bacteria do similar things – principally, they digest complex plant material,” Hammer says. “The fiber we get in our diets bees also get in the form of pollen. Their diet is pretty much entirely nectar and pollen from wildflowers.”

Lactobacilli and Bifidobacteria, considered probiotic bacteria, are present in the guts of both humans and bumblebees.

A Probiotic for Bees

Nancy Moran, Hammer’s postdoctoral advisor at the University of Texas, is a professor of integrative biology and an evolutionary biologist and entomologist who is credited with pioneering the field of research into gut microbiomes in bees.

Moran, whose research mostly is focused on honeybees, points out another similarity between bumblebees and humans. “For both,” she says, “the gut bacteria are highly specialized to live in the host gut and nowhere else. These are not just bacteria picked up here and there in the environment. They come from other hosts, directly or indirectly.”

Moran and Hammer note, of course, that there are also many differences between bee and human microbiomes. And they say the main reason to study bumblebee microbiomes is not necessarily to learn about the human microbiome.

“Disrupted microbiomes are almost always linked to poor health, in bees and in humans,” Moran says. “So understanding the bumblebee microbiome is basic to understanding bumblebees and potentially useful in understanding, and hopefully reducing, the threats to their populations.”

About one-fourth of the 250-plus species of bumblebees worldwide are at risk – Bombus vosnesenskii and Bombus impatiens are not among them – and some are approaching extinction, Hammer notes.

Certain species that were plentiful 50 years ago, based on museum collections, are now almost impossible to find, while others remain abundant, Moran says. In California alone, there are eight species threatened or vulnerable to extinction, she adds.

“Toby’s work is key to understanding what underlies bumblebee health and what threats are impacting their populations,” Moran says. “The gut microbiota has been shown to play a big part in protecting bumblebees from environmental threats, such as newly introduced parasites. Toby’s research group is producing information that is essential for us to discover why certain bumblebee species are disappearing.”

Annika Nelson, an ecologist and postdoctoral researcher in the Hammer lab, currently is studying whether probiotics can be developed for bumblebees to help them thrive. “Many bumblebees in the wild have disrupted gut microbiomes,” she says. “We’re interested in understanding what is causing those disruptions, as well as what the consequences are for bee health.”

Hammer lab manager and researcher Kristal Watrous says she’s keen to work with all the bees she can get her hands on and to learn more about their microbes. She’s a frequent visitor to a vibrant patch of bumblebee habitat at the Niguel Botanical Preserve in Laguna Niguel.

“Professor Hammer’s lab at UCI is a fun and exciting place to work,” Watrous says, noting that research ranges from fieldwork to conducting experiments with bumblebee microcolonies to culturing bacteria from bumblebee guts. “I like that we can run experiments in the lab that help us to understand patterns we observe out in nature.”

And bumblebees are large for insects, which makes them fun to work with, she adds.

“Understanding the bumblebee gut microbiome and how it can change gives us another way to understand their overall health at individual and community levels,” Watrous says. “California has a few species of threatened or endangered bumblebees, and while we aren’t working directly with those species, what we learn in our research could give us tools to help support them.”

Alejandro Vazquez Rodriguez, a fourth-year ecology and evolutionary biology major, has been a member of Hammer’s lab for a little over a year.

“From stingless bees in the tropics to native bumblebees in California, the subject of bee microbiomes is one with many unanswered questions,” he says. “I’m personally interested in learning how these microbial communities impact the health of their hosts, because that’s a relationship that can be expanded to all sorts of animal groups. It’s a component of ecological systems that we know very little about.”