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Genes, early environment sculpt the gut microbiome

Date:

November 28, 2016

Source:

Lawrence Berkeley National Laboratory

Summary:

Environment and genetics
determine relative abundance of specific microbes in the gut, new research
shows. The findings represent an attempt to untangle the forces that shape the
gut microbiome, which plays an important role in keeping us healthy.

Genetics and
birthplace have a big effect on the makeup of the microbial community in the
gut, according to research to be published in the journal Nature
Microbiology.

The findings by a team
of scientists from the Department of Energy’s Pacific Northwest National
Laboratory (PNNL) and Lawrence Berkeley National Laboratory (Berkeley Lab)
represent an attempt to untangle the forces that shape the gut microbiome,
which plays an important role in keeping us healthy.

In the study,
scientists linked specific genes in an animal — in this case, a mouse — to
the presence and abundance of specific microbes in its gut.

“We are starting
to tease out the importance of different variables, like diet, genetics, and
the environment, on microbes in the gut,” said PNNL’s Janet Jansson, a
corresponding author of the study. “It turns out that early life history
and genetics both play a role.”

Scientists studied
more than 50,000 genetic variations in mice and ultimately identified more than
100 snippets that affect the population of microbes in the gut. Some of those
genes in mice are very similar to human genes that are involved in the
development of diseases like arthritis, colon cancer, Crohn’s disease, celiac
disease, and diabetes.

The abundance of one
microbe in particular, a probiotic strain of Lactobacillales, was
affected by several host genes and was linked to higher levels of important
immune cells known as T-helper cells. These results support the key role of the
microbiome in the body’s immune response, and suggest the possibility that
controlling the microbes in the gut could influence the immune system and
disease vulnerability.

“We know the
microbiome likely plays an important role in fighting infections,” said
first author Antoine Snijders of Berkeley Lab. “We found that the level of
T-helper cells in the blood of mice is well explained by the level of Lactobacillales in
the gut. It’s the same family of bacteria found in yogurt and very often used
as a probiotic.”

To do the research,
the team drew upon a genetically diverse set of “collaborative cross”
mice that capture the genetic variation in human populations. Scientists
studied 30 strains of the mice, which were housed in two facilities with
different environments for the first four weeks of their lives. The scientists
took fecal samples from the mice to characterize their gut microbiomes before
transferring them to a third facility.

The researchers found
that the microbiome retained a clear microbial signature formed where the mice
were first raised — effectively their “hometown.” Moreover, that
microbial trait carried over to the next generation, surprising the scientists.

“The early life
environment is very important for the formation of an individual’s
microbiome,” said Jian-Hua Mao, a corresponding author from Berkeley Lab.
“The first dose of microbes one gets comes from the mom, and that remains
a strong influence for a lifetime and even beyond.”

In brief, the team
found that:

• Both genetics and
early environment play a strong role in determining an organism’s microbiome

• The genes in mice
that were correlated to microbes in the gut are very similar to genes that are
involved in many diseases in people

The researchers also
found indications that moderate shifts in diet play a role in determining
exactly what functions the microbes carry out in the gut.

“Our findings
could have some exciting implications for people’s health,” said Jansson.
“In the future, perhaps people could have designer diets, optimized
according to their genes and their microbiome, to digest foods more effectively
or to modulate their susceptibility to disease.”

Story Source:

Materials provided by Lawrence Berkeley National Laboratory. Note:
Content may be edited for style and length.

Journal Reference:

1.    Antoine M. Snijders, Sasha A. Langley,
Young-Mo Kim, Colin J. Brislawn, Cecilia Noecker, Erika M. Zink, Sarah J.
Fansler, Cameron P. Casey, Darla R. Miller, Yurong Huang, Gary H. Karpen, Susan
E. Celniker, James B. Brown, Elhanan Borenstein, Janet K. Jansson, Thomas O.
Metz, Jian-Hua Mao. Influence of early life exposure, host genetics and
diet on the mouse gut microbiome and metabolome. Nature
Microbiology, 2016; 2: 16221 DOI: 10.1038/nmicrobiol.2016.221

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