Researcher studying squid-human bacteria connection

by Tim Crosby

CARBONDALE, Ill. -- Take a look at the probiotic movement among health-conscious people today -- from fermented foods like yogurt to pills containing bacteria -- and it’s easy to see how far humans’ thinking on bacteria has come.

While we spent many years as a culture thinking of bacteria as one of the “bad guys,” the scientific outlook has begun leaning more and more in the direction of our co-existence being more of a partnership than a battle.

Bacteria and their host animals influence one another in fundamental and profound ways, said Bethany Rader, assistant professor of microbiology at Southern Illinois University Carbondale. She focuses on the mechanisms that have evolved to establish and maintain this relationship, with special emphasis on the host’s innate immune system and how it negotiates this beneficial relationship.

“All animals have bacteria that live in them and on them, and these bacteria help our bodies function normally and help keep us healthy,” Rader said. “Thinking about them as the good guys is still a new and exciting topic, and in fact has really started to change how we think about health and medical treatment.”

While all higher order animals -- metazoans -- have lifelong relationships with bacteria, Rader and her students use what some might consider to be an unusual platform to study this symbiotic relationship between a host and so-called “good” bacteria: the Hawaiian bobtailed squid, housed in laboratories on campus.

The squid has a specialized organ that houses a dense bacterial culture. In return for a safe nutrient rich place to live, the bacteria, known as Vibrio fischeri, produce light that camouflage the squid from its predators swimming beneath. It’s a perfect example of an animal and bacteria living together in a mutually beneficial way.

It may seem strange, but squid and humans have a lot in common, on other levels. We share what is known as an “innate immune system,” which is sort of the “first responder,” and it is what causes initial inflammatory response during an infection.

Because of those similarities, researchers expect both human and squid innate immune systems to act in similar ways when they are deciding whether to mount a response against symbiotic bacteria.

Another reason for looking at squid is that the symbiotic organ -- or light organ -- of the squid, is similar to organs in the human body that are colonized by beneficial bacteria. The symbiotic relationship that occurs inside this organ is similar to the symbiosis in its gut, as both involve large populations of bacteria residing in the lumen of an epithelia-lined organ.

Squid also are smaller than rodents, easier to house and they can produce a large number of egg clutches containing a large number of hatchlings, Rader said. Her first group of adult research squid, for example, produced about 4,000 hatchlings in four months, which is something that rodent models could not do. The high numbers allow for more experiments and higher confidence in the results of those experiments, Rader said.

“Since it is unethical and impossible do many of the experiments to answer these questions on humans, we mainly utilize the squid as a model for humans in our lab,” Rader said. “It may seem a little weird to use a squid as a proxy for humans, but they share a lot of organs, organ systems and the innate immune system with us that are similar in structure and function, and are simpler than humans.”

Rader also is looking at how enzymes made by the squid can detoxify a substance known as “endotoxin” that is found in the cell walls of the bacteria in its light organ. Endotoxin exists in the gut of both squid and humans, but usually neither host mounts an immune response to its presence. Understanding this non-response may unlock further treatments for gut maladies.

“We can then collaborate with researchers in drug development and clinical work to apply the knowledge we’ve gained from the squid to develop treatments for people who are undergoing inflammatory bowel diseases that are a result of the endotoxin that is not properly detoxified,” Rader said. “So we are hoping that with this particular project and with other projects in the squid, that we can understand the process of correct partnership so we can develop ways to help people where the partnership has turned toxic.”

Rader and her team also are looking at questions such as how our bodies choose our bacterial partners -- or perhaps how our bacterial partners pick us -- when we are born. Another question she is researching -- how our bacterial partners influence our nervous system during development or after injury – is a cooperative effort with Michael Hylin, assistant professor of psychology at SIU.

Most of the research takes place in the basement at Lindegren Hall, where a series of tanks with cubicles house the male and female squid as well as an egg hatching operation. The National Institutes of Health is funding the research with a three-year, $433,650 grant that is renewable. Eventually, the research may expand to the new Aquatic Research Laboratory in the McLafferty Annex on the far west edge of campus, which would provide room for more collaborative study.

Understanding more about our symbiotic relationship with bacteria, including the bacteria found in our digestive systems, can lead to better treatments for conditions associated with that area, and with other diseases not typically associated with our bacteria, Rader said. Altered intestinal bacterial communities, for instance, are associated with diseases such as rheumatoid arthritis and cirrhosis, and at least in rodents, associated with elevated stress and anxiety-related behaviors.

Overall, the work also could ultimately help medical professionals develop better treatments for ailments such as inflammatory bowel disease, Crohn’s disease, and metabolic disease such as obesity and diabetes, among others.

“We are already implementing what we are learning about the microbiome in the clinical setting,” Rader said.

An extreme, slightly disgusting example that has gained some attention lately is fecal transplant, which involves directly implanting a healthy person’s fecal microbiota into an unhealthy person. Fecal transplants are being utilized as a treatment for severe intestinal inflammatory conditions.

Or it can be as simple as following a doctor’s recommendation to eat yogurt to recover from a course of antibiotic treatment, which can negatively alter microbiota community in the gut.

“It’s a really, really exciting time to be a scientist in this field,” Rader said. “Now everyone can love their bacteria as much as I do!”

Rader’s work soon will be featured on a website called bioGraphic, a multimedia magazine powered by the California Academy of Sciences created to showcase both the wonder of nature and the most promising approaches to sustaining life on Earth.