Beyond synthetic biology, synthetic ecology improves health by changing the environment

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PICTURE: In a new study from Nature Communications, researchers at BU’s Microbiome Initiative found that providing microbial communities with a greater variety of food sources did not increase the variety of microbial species. After

Credit: Image courtesy of Alan Pacheco and Daniel Segrè.

There is a lot of interest right now about how different microbiomes – like the one made up of all the bacteria in our gut – could be harnessed to improve human health and cure disease. But Daniel Segrè set his sights on a much more ambitious vision of how the microbiome could be manipulated for good: “To help support 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 study microbiomes – microscopic communities of bacteria, fungi, or a combination of those that influence them. on each other and on the surrounding environment. . They want to know how microbiomes could be directed to perform important tasks like 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 forests. other plants despite changing environmental conditions.

“Microbes affect us as humans through their own metabolic processes, they affect our planet through what they consume and secrete, they help create the oxygen we breathe”, explains Segrè, professor of biology and bioinformatics at the BU College of Arts & Sciences and College of Engineering professor of biomedical engineering. “A long time ago, microbes were what made multicellular life possible.”

But unlike many other synthetic biologists who work in the improvement or genetic engineering of microbes directly, Segrè is more interested in how to direct the behavior of a microbiome by altering the environmental conditions in which it lives – a an approach which he believes could best be described as “synthetic ecology”.

“The most traditional synthetic biology approach would be to manipulate the genomes of microbes”, explains Segrè. “But we are trying to manipulate microbial ecosystems using environmental molecules.”

“We know that microbial interactions with the environment are important,” says Alan Pacheco, who obtained his doctorate in bioinformatics at the Segrè laboratory. Some of these interactions benefit multiple microbial species, some benefit only one species in a community, and some can be harmful to certain species, he says. “But there’s still so much we don’t know about why these interactions happen the way they do.”

In a new study published recently in Nature Communication, Segrè, Pacheco and their collaborator Melisa Osborne, a research scientist at the Segrè laboratory, explored how the presence of 32 different environmental molecules or nutrients, alone or in combination with others, would influence the growth rate of microbial communities and the mixing of ‘various species. constituting a given microbiome.

“Deep in our minds we had this idea of ​​a diet, framed by studies that looked at differences in the gut microbiome based on Western diets and hunter-gatherer diets,” says Pacheco, who is now a postdoctoral fellow at ETH Zürich. The hunter-gatherer diets, which are opportunistic and include 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 believed to cultivate a healthier gut. .

But the experimental results surprised the team. They expected to see the growth and diversity of microbiomes increase as “insects” have more access to a variety of foods – a range of carbons, including sugars, amino acids and complex polymers – but that’s not what their carefully controlled experiments revealed. Instead, they observed that competition for food between different species of microbes hampered diversification within the microbial community.

“Our results demonstrate that environmental complexity alone is not sufficient to maintain community diversity and provide practical guidance for the design and control of microbial ecosystems,” write the authors.

So what are the mechanisms that control the diversity of a microbiome? “It’s going to take some time to figure out the cause of all of these interactions,” says Segrè.

Although increasing the variety of food sources did not increase the variety of microbial species in their experiments, more food fueled more microbial growth. “We have found that the yield depends on the total number of carbon sources, but not on the variety of those sources,” says Segrè. “It’s like people at a picnic – if enough people come to a picnic, no matter how spread the different foods are, eventually everything will be eaten. In many of our experiments, the microbial communities have used up to the last bit of carbon source at most. “

Pacheco adds that if someone can consume something, someone else can surpass it. “Our experiments have shown that the crucial modulator of microbial diversity is the extent to which these different organisms compete for resources,” he says. “The more organizations compete, the less diverse this community will be.”

The team plans to do more research on other environmental factors, studying how nutrient access and variety alter microbial communities over time, and how the environment in which the microbial community lives affects their consumption and. their secretion of molecules. They are also exploring how metabolic processes among different microbial species might interact and interact with each other, and how the ability of certain organisms to consume multiple resources sequentially or simultaneously affects the microbiome as a whole.

Unlocking more and possibly tapping into all of those environmental “dials and knobs” could open the door to the use of microbiomes to influence human metabolisms and states of health or disease in people and in natural ecosystems.

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Funders: 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, University’s Office of Interdisciplinary Biomedical Research from Boston

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