Symbiotic Parasites, Bacteria, and Other Microorganisms Keep Us Healthy
by Suzanna Engman
The big picture of ecology shows that while the earth is undergoing a revolution—global warming resulting from modern human activity—the human body itself is also undergoing drastic changes. Lifestyles in industrialized societies have created or are increasing the frequency of diseases and epidemics: obesity; heart disease; and autoimmune disorders leading to asthma, ulcerative colitis, allergies, rheumatoid arthritis, and lupus, to name just a few. Scientists believe that these diseases may be the result of disturbances in the human microbiota, a group of microbes that has specific functions in our bodies.
Usually thought of as harmful to humans, bacteria, yeast, parasite, and virus microorganisms actually have co-evolved with us, in symbiotic relationships. They inhabit our nasal, lung, and oral cavities; and the skin, vagina, and gut in mind-boggling numbers. Scientists estimate that the body’s microbial cells outnumber human cells by a ratio of ten to one, which means that there are about a thousand times as many microbial genes as human genes in our bodies.
María Domínguez-Bello, microbial biologist at the University of Puerto Rico, Río Piedras, simultaneously conducts a half-dozen research projects to discover more about our microbiota. They range from microbial studies of the crop content of a neotropical bird species, to the analysis of fecal matter of Amerindians in Venezuela, to microbiota mapping of newborn babies delivered vaginally and by caesarean section.
“Because microbiology was born by linking microbes to diseases, we viewed microbes as always being infectious. And now we are learning that there are good guys. Even the National Institutes of Health, which was always focused on infectious diseases, now has a new project on the microbiome,” says Domínguez-Bello. The Human Microbiome Project, launched in 2007 with $115 million in funding over five years, is characterizing microbiotia, their genetic makeup, gene expression proteins, and metabolic physiologies in relation to health and disease.
Gene sequencing has allowed Domínguez-Bello and other scientists to characterize complex microbial communities and to ascertain commensal microorganisms (organisms in a relationship in which one partner benefits and the other is unharmed) and mutualistic microorganisms (organisms in which both partners benefit). Evolution in humans has selected for mutualistic interactions that promote human health. However, ecological changes, such as overuse of antibiotics and antiseptic lifestyles, can disturb the balance of symbiotic relationships and lead to disease.
“We are an ecosystem,” says Domínguez-Bello. “We are a human niche to our microbiota. If you disturb the balance you get an infection—the loss of balance of that microbiota. In our studies, we want to find out who are the good guys and try to protect them and protect our microbial biodiversity, too.”
The human microbiota, its processes, interactions, and relationships to the human body and to each other, is a relatively recent frontier of scientific scrutiny, but one that promises answers to many health problems. For example, some members of the human microbiota can secrete molecules that inhibit their host’s pathogens or detoxify harmful compounds, which gives the symbiontic microbes opportunities to multiply; whereas other microbes, such as helminthes (parasites such as hookworm and pinworm), that were previously thought to cause diseases can actually prevent many more.
Domínguez-Bello began her studies of microbes by helping to solve a mystery. While cattle and sheep in Mexico and South America could feed freely from the toxic plant Leucaena leucocephalais without ill effect, cattle and sheep in Australia died after eating the plant. It was known that the foliage and pods of the plant, which is endemic to Mexico and South America, contain the toxic amino acid mimosine. Why didn’t the Mexican and South American livestock succumb to the poison? The answer lay in the microbes of the animals’ rumens, microbes that evolved with the ruminants themselves.
The rumen is the first stomach of cows and sheep. Ruminants have a diet made of cellulose and other polymers, for example, hay and woody plants, that is indigestible to them. However, the bacteria in their first stomach ferments these fibers, so the animals actually obtain their nourishment from the bacteria and bacterial products in the rumen. The researchers found that the key to detoxifying leucaena plants was the bacteria in the rumen.
“When Raymond Jones, the Australian researcher who first hypothesized that the microbes might detoxify mimosine, interchanged rumen contents from tropical sheep and Australian sheep, the problem was solved. So that was a hint that one or more microbes were involved,” says Domínguez-Bello. Eventually scientists identified the microbes that degraded the toxins and now one is routinely given as a probiotic to Australian livestock.
A current project of Domínguez-Bello, funded by the National Science Foundation, focuses on the hoatzin (Opisthocomus hoazin), a neotropical bird species that lives in swamps, riverine forests, and mangroves. It is the only known bird with crop fermentation. The researcher wants to find out how diet selection and the gut microbiota contribute to digestive efficiency. To do so, the group of researchers she works with extracts the crop contents in situ and freezes the contents in liquid nitrogen. Then, in the laboratory, they extract DNA, sequence it, and compare the crop contents of different hoatzins. They have found new bacteria never before documented and remarkable bacterial diversity in the crops. These findings may provide important new insights into how diet affects gut microbial communities, how metabolism of carbohydrates is affected by bacteria, and how fermentation provides sufficient energy to the host. These three aspects are relevant to humans, who also have a fermenting organ, the colon.
Another project, a collaboration of anthropologists, doctors, and microbiologists from the Venezuelan Institute of Scientific Research, the Amazonic Center for Research and Control of Tropical Diseases (CAICET by its Spanish acronym), NEw York University, Washington University, Cornell University, and the University of Colorado at Boulder, studies the microbiota of Amerindians in Venezuela.
Scientists know that Amerindians, who live in differing degrees of isolation, do not suffer from many diseases common in developed countries. “We now recognize that we may have lost important members of our microbiota, by the use and abuse of antibiotics and by too much hygiene. We have highly impacted our microbiota. My group wants to know how much we have impacted it, compared with Amerindians. We want to study that gradient and see how the microbiota changes.”
The scientists collect the microbiota by swabbing the mouths of Amerindians and taking samples of their fecal matter. Then they freeze the samples in liquid nitrogen, isolate the DNA, and study the bacteria. The DNA samples are transported to Caracas where they are sequenced. “Whatever information we get from the Amerindians that is useful for us is useful for them, too. They could potentially avoid our mistakes as they integrate into Western lifestyles,” says Domínguez-Bello.
Initially, the researchers studied the nutritional status of Amerindians to look at the link between nutrition and microbes. “We chose a community that lives close to a river where they can fish. Although they have a lot of infectious diseases and child mortality is high—they die of diarrhea—they eat well. The children were well nourished. This was independent of the parasite load and the presence of Helicobacter pylori, which is a bacteria that we study, too. It has traditionally been considered a pathogen in humans, but H. pylori is really a part of the microbiota.”
Helicobacter pylori has been found to cause gastric cancer and ulcers in adults. It lives in the stomachs of humans, but has virtually disappeared in most developed countries. “Against our original hypothesis, we found that children with H. pylori had better nutritional status, not worse. Now we think that H. pylori improves their immunity,” says Domínguez-Bello.
“This bacteria is a double-edged sword. We believe that it is good for children, but then you have to pay a toll after you pass reproductive age. When humans all died at 30 or 40, H. pylori was only good. Now that we have doubled our life expectancy, those microbes with a lifelong inflammatory response cause problems in the long term. H. pylori presents a serious risk of gastric cancer and ulcers in adults.”
Other researchers have found that conventional wisdom regarding iron deficiency also needs to be revisited. “We tend to believe that the formulas in our medicine practices are good for everybody. They are not. Our medical solutions are not universal. When doctors go to the Amazon, for example, and find that people are anemic, they provide iron. However, that has been shown to increase the risk of malaria. In a recent issue of the Journal of Infectious Diseases, a study confirms that routine supplementation with iron and foliate in children can result in an increased risk of severe illness and death in Africa. So, ecology is everything.”
Domínguez-Bello says that human health decisions must be evaluated within their ecological context. Where do they live? What are their risks? These questions must be answered to optimize health accordingly. “It might be that in malaria areas what is optimal is to be a little anemic. But then we have to redefine an acceptable low level of iron. What level will guarantee that children develop well and with normal intelligence levels?”
The researcher’s latest project compares the microbiota of babies born by cesarean section with those born vaginally. Domínguez-Bello thinks that women should avoid unjustified cesareans because the trip through the birth canal provides the newborn with infection fighting microbes. “Nature has made of the birth channel a microbiota containing lactobacilli and 250 species of microbes. Nature is clever. A healthy vagina provides the first microbiota to the baby and is the seed colonizer of the skin, mouth, and intestine.”
As she researches, Domínguez-Bello is aware of her ethical responsibilities. Before studying Amerindian microbiota, she obtained permission from the UPR Internal Review Board and promised to keep the samples anonymous and then destroy them after use.
María Domínguez-Bello earned a BSc in biology at Universidad Simón Bolivar in Caracas, Venezuela and a Msc in animal nutrition and Ph.D. in microbiology at Aberdeen University, Scotland. She was awarded a postdoctoral position in Scotland and France and has worked at Purdue University, Universidad Autonoma de Madrid, and Duke University. Before becoming a researcher at UPR-RP, she and her husband lived and worked at the premier science center of Venezuela, El Instituto Venezolano de Investigaciones Científicas (IVIC). She recalls her years working in the isolated scientific community fondly. “IVIC was built far from Caracas up in the mountains, like a monastery. And that was the best environment because otherwise it would be impossible to work in that country. There’s so much unrest, and that’s true for all of Latin America,” she says. After reaching the seven-year residence limit for scientists living at IVIC, she and her family moved to Caracas, but when crime in Venezuela, including her father’s kidnapping, became unbearable and the political situation split the country in two, Domínguez-Bello and her husband sought positions at UPR-RP. She has one daughter, and when asked about the difficulties involved in balancing motherhood with microbial research, she responded, “I only have one child, so that answers your question, in part.” Her daughter would define her as a workcoholic, but the researcher loves traveling, learning about different cultures, reading, movies, and music. She plays tennis at least once a week and has a passion for nature, scuba diving and camping.