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Whether it's the gut-disease connection or the gut-brain axis, how microorganisms work in the gut is a hot topic—intensely studied.
Dave Burbank
Dave Burbank

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Using the fruit fly as an incredibly instructive model to parallel how microorganisms interact with the human gut, Angela Douglas has made breakthroughs in gut research, particularly the activities that benefit human health.
Dave Burbank
Dave Burbank

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"You can have two insects that are feeding the same amount, on the same food, and the ones with the microorganisms are lean and healthy and the ones without are really fat. They can have five times the lipid content. It's extraordinary."
Dave Burbank
Dave Burbank

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"Biologists often talk about the gut-brain axis, because there's a strong relationship between the gut and the brain."
Beatrice Jin; Dave Burbank
Beatrice Jin; Dave Burbank

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The Douglas lab also studies insect pests—how to interrupt the insect-intracellular bacteria symbiosis as a pest control method. Referring to the insects, "All of them are absolutely dependent on particular bacteria in these special cells."
Dave Burbank
Dave Burbank

How Microbes Benefit Human Health

by Caitlin Hayes

We spend a good deal of energy fighting or avoiding certain microbes—using antibacterial soaps, over-cooking our chicken, and taking antibiotics to fight infection, for example. Over the past decade, however, research has been pointing to the many microbes that are our partners rather than our adversaries.

“When they’re in a hard place, organisms tend to form alliances,” says Angela E. Douglas, Entomology. “I became interested in these mutually beneficial animal-microbial interactions as an undergraduate and never looked back.”

Douglas seeks to understand and elucidate the ways in which our health and the health of animals depends on microbes. She and her team use fruit flies as a model system to study the microbiota of the gut and its effect on metabolism. She also looks at microorganisms essential to the survival of insects that are agricultural pests, searching for new strategies to stop them in their tracks.

Microbes, Cutting Calories in the Gut

One of the major findings in Douglas’ lab is that microbes living in the gut of fruit flies protect them from obesity. “You can have two insects that are feeding the same amount, on the same food, and the ones with the microorganisms are lean and healthy and the ones without are really fat,” Douglas says. “They can have five times the lipid content. It’s extraordinary.”

The microbes contribute to the metabolic health of the insects in several ways. First, they consume some of the calories the animal takes in through its diet, a phenomenon Douglas hypothesizes has a parallel in humans. “In the small intestine in humans, there are bacteria that have similar capabilities, and we strongly suspect that these bacteria contribute to good health by competing for excess calories,” she says.

By mechanisms not yet fully understood, the microbes in flies also promote the degradation of lipid, so that flies with their microorganisms intact degrade fats faster. The whole animal, according to Douglas, is metabolically more active if they have a healthy community of microbes.

Douglas’ team is now probing the mechanisms of this at the cellular and molecular level. “Having established that the microorganisms and microbial communities have this or that effect on the metabolic health of the host—what are the actual molecules involved?”

All this work is done in the Drosophila fruit fly, a model which continues to provide so much information about our own systems, Douglas says. “We can do fundamental work more cheaply and more humanely working with flies,” she adds. “And it’s lovely to see the connections between the different systems.”

The Connection between Gut Microbes and Obesity, Brain Health, and More

If gut microbial communities protect against obesity, those communities are obviously desirable, and a number of products, especially yogurts, are now marketed as promoters of healthy gut flora for people. But another finding in Douglas’ lab points to the idea that not all microorganisms may work for all people.

“It actually matters what the microorganism is. Some are more protective against obesity than others, and it also depends on the genotype of the host,” Douglas says. A microbial community that’s known for protecting against obesity may not work for every genome.

“One of the things we’re investigating is what genes and aspects of the genetic makeup of the insect makes them responsive to a microbial community or less responsive,” Douglas says.

This means looking closely at which microbial genes are responsible for conferring protection and which genes in the insects are affected. Douglas and her team have found that many of the responsive fly genes make perfect sense. They are related to metabolism. There have also been some surprises.

“A lot of the genes are related to the function of the nervous system, and there’s increasing evidence that these microorganisms are interacting directly or indirectly with nervous system function,” Douglas says.

“Various neurodevelopmental diseases like autism and neurodegenerative diseases like Parkinson’s or Alzheimer’s have some gut-related symptoms that correlate with the nervous system function.”

Not only do the microorganisms in the gut impact metabolism, they also seem linked to the health of the nervous system, the complex system of nerves responsible for sending signals to and from the brain and spinal cord. “Biologists often talk about the gut-brain axis, because there’s a strong relationship between the gut and the brain,” Douglas says. “In fact, various neurodevelopmental diseases like autism and neurodegenerative diseases like Parkinson’s or Alzheimer’s have some gut-related symptoms that correlate with the nervous system function. Now, people are increasingly thinking that it isn’t just a gut-brain axis but a gut-microbe, gut-brain axis.”

Researchers suspect the microbial activity in the gut, in other words, is related to nervous system and brain health, too. “Our data are saying, you bet,” Douglas says.

Targeting Bacteria in the Cells of Insects for Pest Control

Another branch of research in the Douglas lab investigates a symbiosis of a different sort—that between insect pests and intracellular bacteria. These bacteria live inside special cells of the insects and play a key role in the hosts’ survival.

The insects studied here are the bane of gardeners and farmers—aphids, white flies, scale insects, plant hoppers and leafhoppers, which feed on plant sap. Many also transmit plant viral diseases. “They’re really, major, major pests,” Douglas says. “And all of them are absolutely dependent on particular bacteria in these special cells.”

The bacteria help the insects carry out a crucial nutritional conversion—converting nonessential amino acids produced by the host into essential amino acids that the insect is incapable of producing on its own. “I’ve compared it to alchemy, the low product like lead going in and gold coming out,” Douglas says.

If scientists can interfere with this process, they could provide a new strategy to control these pests. “So we’ve been doing a lot of work to demonstrate that these nutrients are released and to understand what controls their release and production and to identify key ways we can interfere with it,” Douglas says.

Douglas’ team has established that the amount of essential amino acid produced by the bacteria is directly related to the amount of substrate given to it by the host. If scientists can therefore limit the production of the substrate, they may be able to reduce the populations of the insect pests. “We think this is generalizable across many different pests,” Douglas says.

Along the way to this broad solution, the lab has recently made a breakthrough specific to aphids. They found that they can suppress a host enzyme that masks the cell wall of intracellular bacteria from the aphid’s immune system. With the enzyme, the immune system ignores the bacteria, but without it, the immune system attacks. With the bacteria suppressed, the destructive aphids can’t survive. “It’s really very encouraging,” Douglas says.

The lab is also optimizing the use of RNAi (RNA interference) to suppress the activity of the genes that are crucial for symbiosis function. “RNAi offers a route for very specific targeting of the insect pest species, without deleterious effects on other organisms, especially natural enemies of the insect pests and pollinators,” Douglas says. 

The Beneficial Alliances of Animals and Microbes, Now a Popular Topic

Research about the alliances between animals and microorganisms is having a heyday. But when Douglas first started, the field wasn’t yet established—and the beneficial interactions between animals and microbes were seen as trivial, a curiosity of nature maybe, but not a driving factor of health or disease.

“At that time, there was this strong view in the biological disciplines that antagonistic interactions made the world go round,” Douglas says. “Everything was competition, predation, and a little bit of parasitism. But I felt objectively that’s not what I was seeing.”

Douglas observed different organisms entering into mutually beneficial partnerships that enabled them to tolerate stressful conditions. “I felt this notion that life is all about antagonistic interactions was missing a really important thread,” she says.

Now that the world has caught up with her field, Douglas says the questions for her and her colleagues haven’t changed, but more people are interested in the answers. “It’s really very gratifying,” she says.