U. WASHINGTON (US) — For the first time, the vast array of bacteria in the human gut has been studied as a complex, integrated biological system, rather than a set of separate species.
The new approach, which reveals patterns that correspond with body weight, treats the human microbiome as a cohesive “supra-organism,” in which genes from multiple microbial species act in concert, as if they were part of a single organism, says Elhanan Borenstein, assistant professor of genome sciences at the University of Washington.
Researchers know that obese and lean people have differences in their gut microbiome, but a comprehensive, system-level understanding of how these variations affect energy production, use, and storage, remains unclear. (Credit: Elhanan Borenstein)
“Our research introduces a novel framework, applying systems biology and in-silico (computer) modeling to study the human microbiome—the complex ensemble of microorganisms that populate the human body—as a single cohesive system,” he explains.
People harbor more than 100 trillion microbes that live in various habitats on and within the human anatomy; the gut houses the densest population of all, containing hundreds of bacterial species. Their collective gene set is enormous: 150 times larger than the set of human genes.
The gut microbiome helps keep us alive by manufacturing vitamins and the building blocks of proteins, extracting energy from food, and conferring disease resistance.
“Characterizing the gut microbiome and its interactions with its human host has the potential to provide deep insight into normal human physiology and disease states,” says Sharon Greenblum of the department of genome sciences and first author of the study paper published in the Proceedings of the National Academy of Sciences.
Researchers have already observed that obese and lean people have differences in their gut microbiome. What preliminary findings are still missing, according to Borenstein, is a comprehensive, system-level understanding of how these variations in the genetic makeup of the microbiome affect its organization and consequently its metabolic potential (energy production, use and storage) and its effects on the human host.
Borenstein’s team obtained datasets derived from two previous studies describing the set of genes in the gut microbiomes of lean and obese individuals and patients with inflammatory bowel disease.
The team used advanced computational techniques to reconstruct models of these microbial communities and the interactions between the various genes. The group also estimated the change in abundance of enzymes associated with the various host states: lean, obese, or affected with inflammatory bowel disease.
Their models reflected metabolic interdependencies between enzymes, not their physical location in the gut. Certain interactions were central to the microbial community’s metabolism. However, those enzymes that typified obesity or leanness were mostly remote from the core network and its key metabolic functions. These enzymes worked in the periphery of the modeled network. These peripheral enzymes may represent metabolic first steps relying on substances not manufactured by the microbiome or end points releasing products not used by the microbiome, the researchers surmise.
Such enzymes, Borenstein explains, are likely to directly use or produce substances that characterize the gut environment and form an interface between microbial and human metabolism.
“Our results suggest that the enzyme-level variation associated with obesity and inflammatory bowel disease relates to changes in how the microbiome interacts with the human gut environment, rather than a variation in the microbiome’s core metabolic processes,” Borenstein says.
Researchers from Harvard University participated in the research.
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