Nature Sub-Journal: Monitoring bacterial strains, not just species

Every day, billions of bacteria in your digestive system are changing; the food you eat, the medications you take, and the bacteria you are exposed to make some bacteria multiply more than others

In the past ten years, scientists have provided a general description of the human microbiota by describing the types and numbers of bacteria present in the human intestine

Bacterial strains are a bit like dog breeds or tomato breeds.

Pollard, director of the Gladstone Institute of Data Science and Biotechnology and the lead author of the two studies, said: "I think that researchers just focus on microbial species and miss a lot of information

In a study published in the journal Nature Biotechnology, Pollard’s laboratory collaborated with Dr.

Chunyu Zhao (left), Jason Shi (middle) and Katie Pollard (right) are members of the team that devised a new algorithm to identify bacterial strains

In another paper published in the online edition of "Genome Research", Pollard collaborated with the laboratories of Dr.

Make the microbiome meaningful

In your gut, bacteria may not only digest your food

Since every type of bacteria has its own genetic code, scientists rely on DNA sequencing to discover which bacteria are in a person's microbiome

So far, identifying genetic differences in microbiome samples requires high-performance computing power and cloud storage, which most laboratories do not have

"The algorithm for analyzing genetic sequences was developed for the human genome," said Pollard, who is also a professor at the University of California, San Francisco and a researcher at the Zuckerberg Center for Biological Research

Pollard and her colleagues know that long-term genome sequences are common in many bacterial species or strains

The researchers analyzed more than 100,000 publicly available high-quality genomes of about 900 bacteria commonly found in the human intestine

With the proliferation of newly sequenced genomes in the gut microbiota and other environments, we can now create detailed genetic maps for thousands of bacteria.

This field of research has previously been limited because only a few laboratories in the world have funds or computer hardware to analyze microbiome data at strain resolution
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Pollard said: "Our new algorithm opens the door for everyone to achieve this level of resolution on a personal computer
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Before and after antibiotics

In recent years, a question that microbiome researchers have been trying to answer is how much a person’s microbiome changes over time
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This problem has been solved at the species level; scientists have tracked how the species composition of the human microbial community changes with changes in diet, disease, or the environment
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But the results of the study failed to explain how the microbiome acquired new functions, such as antibiotic resistance or the ability to inactivate chemotherapy drugs, because the species composition remained stable every month
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Pollard and her colleagues hope to investigate this issue in depth by analyzing how bacterial strains, not just species, change over time
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They redesigned a method for sequencing individual human cells and used it to encode bacterial DNA molecules
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This allowed the research team to track a single strain in a person during the five-month study
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The research team sequenced the microbiome of a healthy person approximately once a week for 5 months
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During this period, the subject was accidentally diagnosed with Lyme disease and received a 2-week course of antibiotics, which is known to eliminate a variety of bacteria, including those living in the human intestine
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Goode, an assistant professor of applied physics at Stanford University, said: "We assume that many microorganisms will become less abundant under the action of antibiotics and then recover, but the final microbiome will be more or less similar to the microbiome at the beginning
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In some cases, this is true, certain types and strains of microorganisms are very resilient, and at the beginning and end of 5 months, there is almost no change in the genome
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But in other cases, the strains that emerged after antibiotics were genetically different from the strains at the beginning, even though the abundance of the species did not change
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Importantly, if the team only analyzes the species present in each microbiome sample, these differences will be ignored
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Although the GT-Pro algorithm is not yet available for this research, Pollard said it will make similar research easier and cheaper to conduct in the future
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Map new paths for microbiome research

The bacteria in your body is like a jungle-a vibrant, ever-changing ecosystem where organisms coexist in a delicate balance
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When viewing satellite images from above, ecologists can monitor the deepest and most dramatic changes in the jungle, but they will miss the finer complex factors that shape the environment
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Similarly, those who study the microbiome by observing changes in species have a higher understanding of the web and only see the most obvious connections to health and disease
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But Pollard said that with the new perspectives of GT Pro and microbial strains, new connections will become apparent
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Pollard said: "There is still a lot of work to be done to understand the functional consequences of microbiome differences
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But so far, we have not had the right measurement tools to ask these questions, and now we have them
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