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A “Who’s Who” of the Gut Microbial Community: Their Origins and Health Effects

Researchers have used new and creative methods to identify specific bacterial strains from the microbial communities of humans, other organisms, and habitats on land and sea; learn how they colonize the gut; and determine their impacts on host health and disease. The human gut is home to an estimated 100 trillion bacterial cells, the composition of which varies greatly between individuals. Unraveling the mystery of which microbes are present in the gut, how they come to reside there, and their health implications for the host is the subject of recent investigations by one research group.

One study focused on the question of how microbes colonize the mammalian gut. Scientists used the inventive approach of testing how microbes from non‑native sources compete for resources and space in the intestinal environment. The scientists transplanted male mice raised under sterile conditions with microbes from a wide range of sources, including the guts of humans, zebrafish, and termites; skin and tongue of humans; or from the soil or a marine estuary. They conducted successive stages of experimentation in which microbes were shared between the original transplanted mice and other mice, using transplantation of intestinal contents and/or co‑housing in the same cage. Over a few weeks, they collected fecal samples from the mice and analyzed the genetic material to identify bacterial species present. In their primary set of experiments, they set up mixed groups of transplanted mice rooming together, with some surprising results. For example, one group living arrangement consisted of four mice—one colonized by soil microbes, a second by termite gut microbes, a third by zebrafish gut microbes, and a fourth without any microbes. In this setup, the gut microbes of the four mice quickly came to resemble one another, with species from the soil and zebrafish gut dominating early on; however, after a week, the soil sample-derived microbiome became predominant in all the cohabitating animals. A single type of soil bacteria, a previously unidentified Ruminococcus, proved particularly successful at seizing the opportunity to colonize the mouse gut, likely aided by its ability to process multiple types of carbohydrates in the gut. In another experiment, mice were transplanted with gut microbes from humans living in three very different environments (urban United States, rural Malawi, and the Venezuelan state of Amazonas, with its large population of indigenous peoples). The mice were then co‑housed to develop a roughly average mix of human microbes. The mice harboring a composite human gut microbial mix were then housed in a cage with both mice transplanted with a composite of mouse gut microbes and mice without any gut microbes. Early on, human gut microbes dominated, even in the guts of mice with native mouse gut microbes. After 4 days, the mouse microbes were starting to overtake the invaders from the human gut, though the human gut microbes remained detectable weeks later. These experiments help to define the “succession” of bacterial species as they come to colonize sequentially and compete with each other in the unique environment of the mammalian gut. In addition, the researchers also measured some of the molecules related to bacterial (and host) metabolism, such as carbohydrates, short chain fatty acids, and bile acids, which help these species succeed in outcompeting others in the gut.

Another research project took a new approach to the problem of conducting a census of gut bacteria and providing valuable insights into their health effects. The scientists used combinations of gut microbes harvested from human stool samples and tested them in male mice raised under sterile conditions to be free of any microbes. Two weeks after transplanting the human gut microbes into the mice, they measured increases in a type of immune cell that prevents inappropriate inflammation in the gut, but they also saw an increase in fat deposits (adiposity). Using one of the human donors’ samples as a representative, the researchers sequenced the bacterial genomes present. They identified 17 unique bacterial strains that, when given to mice, showed effects on immune cells and adiposity similar to the effects of the initial bacterial transplants. To find out which specific combinations of bacterial strain subsets were responsible for these effects, the researchers gave 94 different combinations of the bacteria as well as single bacterial strains to the mice. They then measured immune cells, adiposity, and products of nutrient metabolism, such as bile acids, fatty acids, and amino acids, and compared the results to measurements of the same elements in control mice that remained bacteria-free. Through these experiments, they identified which bacteria, alone or in combination, promoted these immune and metabolic functions. For example, they found several bacterial strains were associated with increased adiposity, including five strains in the bacterial group Bacteroides, two strains of Bacteroidetes, and Escherichia coli. Many of the same Bacteroides strains were also associated with expansion of the population of immune cells called regulatory T cells in the intestine.

These studies add to the storm of new knowledge about the mammalian gut microbial community, in terms of understanding the succession of species during colonization and teasing out effects of individual bacterial strains. This work also provides a new means for scientists to identify which resident gut microbes are helping or hindering their human hosts, in terms of key health indicators such as immune function, nutrient metabolism, and fat mass. These methods could be used in the future to identify probiotics or prebiotics—beneficial bacteria or the nutrients they rely on—to enhance human health and limit disease.