GUT BACTERIA ARE PROTECTED BY HOST DURING ILLNESS
To protect
their gut microbes during illness, sick mice produce specialized sugars in the
gut that feed their microbiota and maintain a healthy microbial balance. This
protective mechanism also appears to help resist or tolerate additional harmful
pathogens, and its disruption may play a role in human diseases such as Crohn's
disease, report scientists from the University of Chicago in Nature on Oct 1.
Both hosts and their
gut microbiota can suffer in the case of sickness, but this mutually beneficial
relationship is guarded by the host," said study senior author Alexander
Chervonsky, MD, PhD, chairman of the Committee on Immunology at the University
of Chicago.
When faced with
systemic illness, animals eat less to conserve energy instead of foraging for
food and to deprive pathogens of nutrients. However, this can harm beneficial
gut bacteria, which have an important role in health and disease.
To investigate how
microbiota might be supported during illness, Chervonsky and his team focused
on a potential internal resource produced by the host -- L-fucose, a sugar
which has been shown to affect gut microbes. A host cannot use L-fucose for
energy, but when bound to proteins, it can be used by microbes as a food
source. Under normal conditions, however, the small intestine of mice produces
almost no L-fucose.
The team exposed
different types of mice to a molecule that mimicked a systemic infection. The
mice became sick -- eating less food, drinking less water and losing weight.
Only a few hours after this induced sickness, the researchers observed that
L-fucose was produced and present on almost every surface of the small
intestine. This effect was seen only in response to illness.
The researchers then
tested genetically engineered mice lacking Fut2, the gene responsible for
L-fucose production. Healthy under normal conditions, mice without Fut2
regained weight after induced sickness -- a measure of recovery -- much slower
than their normal counterparts. However, only mice with both intact gut
microbiota and the ability to produce L-fucose recovered efficiently.
"Mice that can
produce L-fucose recover better than those that can't," Chervonsky said.
"If you remove bacteria the effect goes away."
The team used
genetic analyses to confirm that gut microbes were affected metabolically by
the production of L-fucose. As part of this analysis, they noted that sick mice
without Fut2 had significantly greater expression of harmful microbial genes
than normal mice. Hypothesizing that L-fucose production was somehow preventing
opportunistic bacteria from expressing virulent genes, they exposed mice to a mild
bacterial pathogen and then four days later induced sickness. Under this
condition, mice without Fut2 lost significantly more weight than normal,
suggesting that the production of L-fucose helps the host tolerate or resist
additional harmful pathogens.
Interestingly,
around 20 percent of humans lack a functional gene to produce L-fucose, a
problem that has been associated with the inflammatory bowel ailment known as
Crohn's disease.
"We speculate
that without L-fucose, the activation of virulence genes cannot be blocked, and
that's why bacteria play a role in Crohn's disease," Chervonsky said.
"Whether we can use this toward therapeutics in the future requires
further study."
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