Gut microbes in humans and other mammals heavily influenced by diet, says new study

You are what you eat whether you're a lion, a giraffe or a human -- at least in terms of the bacteria in your gut.

A new study led by the Washington University School of Medicine and involving the University of Colorado Boulder shows gut microbial communities in humans and in a wildly diverse collection of mammals carry out core physiological functions that are heavily influenced by whether they are carnivores, herbivores or omnivores.

The researchers sequenced intestinal microbes in stool samples from 33 mammalian species living in the wild or in zoos in St. Louis and San Diego. In addition to identifying the bacterial species living in the mammalian intestines, they characterized the pool of genes present in each microbial community and their related functions, said senior study author Dr. Jeffrey Gordon of the Washington University School of Medicine in St. Louis.

CU-Boulder professor and study co-author Rob Knight said despite the wide variation of mammals selected for the study, the different gut microbial communities share a set of standard metabolic functions common to all species that play a key role in digestion and immune health. Understanding the variation in human microbial intestine communities holds promise for future clinical research, said Knight, a faculty member in the chemistry and biochemistry department and the computer science department.

A paper on the subject was published in the May 20 issue of Science. Other co-authors on the study included CU-Boulder's Justin Kuczynski, Dan Knights, Jose Clemente and Antonio Gonzalez, Washington University School of Medicine's Brian Muegge and Luigi Fontana, and Bernard Henrissat of the Archictecture et Fonction des Macromolecules Biologiques in Marseille, France.

"This was the first time we were able to relate the microbial community members to the specific metabolic functions that were being performed," said Knight, who also is a Howard Hughes Medical Institute Early Career Scientist. "This is surprising because even members of the same bacterial species can have genomes that are up to 40 percent different in terms of gene content."

The team extracted DNA from the mammals and humans and used powerful computer methods to sort gene fragments and match them to the DNA of known organisms.

While there was considerable variation of bacterial gut communities between animals, the study showed many of the same microbial genes were found in all of the digestive tracts, with differences in their relative abundance dependent on whether they were meat-eaters, vegetarians or omnivores. Among the mammals whose fecal material was used to sequence gut bacteria microbes included giraffe, bighorn sheep, gazelle, kangaroo, hyena, lion, polar bear, elephant, gorilla, baboon, black bear and squirrel.

The team also showed how diet influences microbial communities in the human gut by sampling 18 lean people who purposely had cut their caloric intake by 25 percent or more using many different dietary strategies. The researchers found that the functions of gut microbes varied according to how much protein the individuals ate, and the bacterial species varied according to how much fiber was consumed.

In a related 2009 study led by CU-Boulder's Knight, researchers developed the first atlas of microbial diversity across the human body, charting wide variations in microbe populations from the forehead and feet to noses and navels of individuals. One goal of human bacterial studies is to find out what is normal for healthy people, which should provide a baseline for studies looking at human disease states, said Knight, who also is a fellow at CU's Colorado Initiative for Molecular Biotechnology.

"If we can better understand this microbial variation, we may be able to begin searching for genetic biomarkers for disease," said Knight. It might someday be possible to identify sites on the human body, including the gut, that would be amenable to microbial community transplants with either natural or engineered microbial systems that would be beneficial to the health of the host, he said.

"Because the human microbiome is much more variable than the human genome, and because it also is much easier to modify, it provides a much more logical starting point for personalized medicine," he said.

The latest findings emphasize the need to sample humans across the globe with a variety of extreme lifestyles and diets, including hunter-gatherer groups, said the researchers. Such studies could provide insight into the limits of gut bacteria variation and the possibility that human microbes co-evolved with human bodies and cultures, shaping our physiological differences and environmental adaptations.

Members of Knight's lab and their many collaborators are studying how the human microbiome -- all of a person's hereditary information -- is assembled in different people and how it varies in conditions such as obesity, malnutrition and Crohn's disease. In addition to financial support from HHMI, Knight also has been supported by National Institutes of Health funds to develop new computational tools to better understand the composition and dynamics of microbial communities.

The Science magazine study was supported by the NIH and the Crohn's and Colitis Foundation of America.

-CU-

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