How good gut bacteria help reduce the risk for heart disease
Researchers identify a protein responsible for bacteria's beneficial
behavior

Date:
July 8, 2020
Source:
Ohio State University
Summary:
Scientists have discovered that one of the good bacteria found in
the human gut has a benefit that has remained unrecognized until
now: the potential to reduce the risk for heart disease.



FULL STORY ========================================================================== Scientists have discovered that one of the good bacteria found in the
human gut has a benefit that has remained unrecognized until now: the
potential to reduce the risk for heart disease.


==========================================================================
The bacteria's activity in the intestines reduces production of a chemical
that has been linked to the development of clogged arteries. After it's manufactured in the gut, the chemical enters the bloodstream and travels
to the liver, where it is converted into its most harmful form.

The Ohio State University researchers have traced the bacteria's behavior
to a family of proteins that they suspect could explain other ways that
good gut organisms can contribute to human health. In essence, these
microbes compete with bad bacteria for access to the same nutrients in
the gut -- and if the good bacteria win, they may prevent health problems
that can result from how the body metabolizes food.

Much more work is ahead, but the scientists see potential for this
microbe, Eubacterium limosum, to be used for therapeutic purposes in
the future.

Previous research has already shown the bacterium is "good" because it
calms inflammation in the gut.

"Over the last decade, it has become apparent that bacteria in the human
gut influence our health in many ways. The organism we studied affects
health by preventing a problematic compound from becoming a worse one,"
said Joseph Krzycki, professor of microbiology at Ohio State and senior
author of the study. "It's too soon to say whether this bacterium
could have therapeutic value. But that's what we're working toward."
The research appears online and will be published in a future edition
of the Journal of Biological Chemistry.



==========================================================================
The chemical linked to the clogged arteries that characterize
atherosclerosis is called trimethylamine, or TMA. It is produced during metabolism when some intestinal microbes -- generally the bacteria
considered unhelpful to humans - - interact with certain nutrients from
food. Among those nutrients is L- carnitine, a chemical compound found
in meat and fish that is also used as a nutritional supplement to improve recovery after exercise.

Krzycki and his colleagues discovered that E. limosum interacts with L- carnitine in a different way in the gut, and that interaction eliminates
L- carnitine's role in production of TMA (other nutrients also participate
in TMA production in the gut).

The researchers attribute the bacteria's beneficial behavior to a
protein called MtcB, an enzyme that cuts specific molecules off of
compounds to help bacteria generate energy and survive. The process is
called demethylation, and involves the removal of one methyl group -- a
carbon atom surrounded by three hydrogen atoms -- to change a compound's structure or function.

"The bacterium does this for its own benefit, but it has the downstream
effect of reducing the toxicity of TMA," Krzycki said. "Up until now, the
only known gut microbial reactions with L-carnitine involved converting
it into its bad form. We've discovered that a bacterium known to be
beneficial could remove a methyl group and send the resulting product
down another pathway without making any other harmful compounds in the process." In these interactions, L-carnitine functions as a growth
substrate -- a compound consumed so the organism can live and grow,
and also a target for enzyme activity. In the study, the researchers
fed E. limosum cultures an assortment of potential substrates, including L-carnitine. Only when offered L- carnitine did the microbe synthesize
the MtcB protein specifically to lop off L-carnitine's methyl group --
in essence, MtcB is part of the bacteria's natural way to consume the
nutrient.

Krzycki said finding this one significant health benefit in one species
of gut bacteria suggests there is still a lot to learn about how gut
bacteria can influence health outcomes associated with human metabolism.

"MtcB is part of a family of proteins with thousands of representatives
that may use different compounds and change what nutrients bacteria
consume in the gut," he said. "These proteins may behave very similarly chemically, but using different compounds obviously can create big
changes as far as biology goes." This work was supported by grants from
the National Institutes of Health.


========================================================================== Story Source: Materials provided by Ohio_State_University. Original
written by Emily Caldwell. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Duncan J. Kountz, Edward J. Behrman, Liwen Zhang, Joseph A. Krzycki.

MtcB, a member of the MttB superfamily from the human gut acetogen
Eubacterium limosum, is a cobalamin-dependent carnitine demethylase.

Journal of Biological Chemistry, 2020; jbc.RA120.012934 DOI:
10.1074/ jbc.RA120.012934 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200708150606.htm

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