BU scientists are studying how environmental molecules can be used to create “designer” microbiomes to fight disease, pollution, and more
Photo credit: Image courtesy of Alan Pacheco and Daniel Segrè.
There is currently a lot of interest in how various microbiomes – like the one made up of all bacteria in our gut – could be used to improve human health and cure diseases. But Daniel Segrè has a much more ambitious vision in his sights on how the microbiome could be manipulated in a sustainable way: “To preserve our planet, not just our own health.”
Segrè, director of the Boston University Microbiome Initiative, says he and other scientists in his field of synthetic and systems biology are studying microbiomes – microscopic communities of bacteria, fungi, or a combination of these that affect each other and the environment. They want to know how microbiomes could be directed for important tasks such as absorbing more atmospheric carbon, protecting coral reefs from ocean acidification, improving the fertility and yield of agricultural land, and supporting the growth of forests and other plants despite changing environmental conditions .
“Microbes influence us as humans through their own metabolic processes, they influence our planet through what they consume and secrete, they help create the oxygen we breathe,” says Segrè, professor of biology and bioinformatics at the BU College of Arts & Sciences, and a College of Engineering Professor of Biomedical Engineering. “A long time ago, microbes made multicellular life possible.”
But unlike many other synthetic biologists who work to directly improve or genetically modify microbes, Segrè is more interested in how to control the behavior of a microbiome by optimizing the environmental conditions in which it lives – one approach which, in his opinion, could be better described as “synthetic ecology.”
“The more traditional synthetic biology approach would be to manipulate the genomes of the microbes,” says Segrè. “But we try to manipulate microbial ecosystems with environmental molecules.”
“We know that microbial interactions with the environment are important,” says Alan Pacheco, who did his PhD in bioinformatics in Segre’s laboratory. Some of these interactions benefit multiple microbial species, others only benefit one species in a community, and some can be harmful to specific species, he says. “But we still don’t know why these interactions work out the way they do.”
In a new study recently published in. has been published Nature communication, Segrè, Pacheco, and their collaborator Melisa Osborne, a researcher in Segre’s laboratory, studied how the presence of 32 different environmental molecules or nutrients, alone or in combination with others, would affect the rate of growth of microbial communities and the mix of different species forming a given microbiome.
“We had this idea of nutrition in the back of our minds, framed by studies that examined differences in the intestinal microbiome based on Western nutrition compared to hunters and gatherers,” says Pacheco, who is now a postdoctoral fellow at ETH Zurich. Hunter-gatherer diets, opportunistic and with a wide range of plant-based food sources, are considered to be much more diverse than the Western diet, which is why the hunter-gatherer diet is said to promote a healthier bowel.
But the experimental results surprised the team. They expected the growth and diversity of microbiomes to increase as the “beetles” had more access to a variety of foods – a range of carbons, including sugars, amino acids, and complex polymers – but their carefully controlled experiments did not reveal that. Instead, they observed that competition for food between different species of microbes hampered diversification within the microbial community.
“Our results show that the complexity of the environment alone is not enough to sustain the diversity of communities and offer practical guidelines for the design and control of microbial ecosystems,” the authors write.
So what are the mechanisms that control the diversity of a microbiome? “It will take some time to find out the cause of all these interactions,” says Segrè.
Although increasing the variety of food sources did not increase the variety of microbial species in their experiments, more food promoted microbial growth. “We found that the yield depends on the total number of carbon sources, but not on the diversity of these sources,” says Segrè. “It’s like a picnic – if enough people come to a picnic, no matter how the different foods are distributed, everything will eventually be eaten. In many of our experiments, the microbial communities have completely used up every last bit of carbon source. “
Pacheco adds that if someone can consume something, someone else can surpass them for it. “Our experiments have shown that the key modulator of microbial diversity is how much these different organisms compete with one another for resources,” he says. “The more organisms compete with each other, the less diverse this community will be.”
The team plans to explore more environmental factors to study how nutrient access and diversity change microbial communities over time, and how the medium in which the microbial community lives affects their consumption and secretion of molecules. They also study how metabolic processes between different microbial species interact and can interact with one another and how the ability of some organisms to consume multiple resources in succession or at the same time affects the microbiome as a whole.
The further development and eventual use of all of these environmental “dials and buttons” could open doors to the use of microbiomes to affect human metabolism and the health or disease states of humans and natural ecosystems.
Sponsor: Howard Hughes Medical Institute, National Academies of Sciences, Engineering, and Medicine, Ford Foundation, US Department of Energy, National Institutes of Health, National Science Foundation, Human Frontiers Science Program, Boston University Interdisciplinary Biomedical Research Bureau
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