[ad_1]
UVA Discovery Reveals How Gut Microbes Direct
Body’s Biological
Clock
CHARLOTTESVILLE, Va., Aug. 30, 2022
– A new discovery from the University
of Virginia School of Medicineabout how the microbes in
our guts regulate the body’s biological clock could help
us battle sleep disorders, combat jet lag, fight off
foodborne illness and even improve chemotherapy
outcomes.
A research team led by UVA’s Sean Moore,
MD, MS, and Jason Papin, PhD, used miniature “guts in a
dish” and advanced computer modeling to reveal how
microscopic organisms that naturally live in our guts direct
the timing of daily activities of the cells lining our
intestines. These activities, such as absorbing nutrients
from food, are essential to good health; disruptions of the
intestinal cells’ “circadian rhythms” have been linked
to obesity, ulcers, diarrhea, inflammatory bowel disease and
other health problems.
The new research, from UVA’s
TransUniversity
Microbiome Initiative and collaborators, sheds light on
how unique byproducts produced by our gut bacteria reset the
internal clock that sets the schedule for when intestinal
cells carry out their vital jobs. With this information,
doctors may be able to target our gut microbes to improve
patients’ health, battle disease and possibly even reset
our internal clocks when we travel to reduce jet
lag.
“UVA post-doctoral scientist Dr. Deborah
Luzader, research assistant Dr. Jibraan Fawad and pediatric
gastroenterology fellow Dr. Craig McKinney found that
organoids or ‘miniguts’ – derived from either the
small intestine or colon of mice and patients – provide a
new platform for exploring circadian timekeeping between
intestinal epithelial cells and a simplified, but complete,
gut microbiome,” said Moore, a pediatric
gastroenterologist at UVA
Children’s. “Data scientists in the Papin and Moore
labs – Gabe Hanson, Dr. Greg Medlock and Dr. Tom Moutinho
– applied powerful tools from systems biology and machine
learning to narrow down a daunting list of hundreds of
bacterial metabolites to a short list of three of four prime
suspects responsible for the dramatic resetting of
intestinal clock we observed when cells were exposed to
metabolites from certain bacteria. By combining organoid,
microbiome, metabolomic and machine-learning approaches, we
established a chain of causality between specific microbes,
their metabolites and their effects on the
clock.”
Like Clockwork
The UVA scientists
found that gut microbes regulate our intestinal cells by
manufacturing what are called short-chain fatty acids. These
particular fatty acids are only made by gut bacteria and
switch certain mammalian genes on and off as needed over
24-hour periods. That makes them a critical timekeeper for
important biological processes.
The scientists were
able to study this in the lab using “three-dimensional gut
organoids” – essentially, tiny guts in a dish. The
researchers began using mouse organoids but then were able
to reproduce their findings using human
cells.
Determining where to start, though, was quite a
challenge. The interactions between gut microbes and our
bodies are terribly complex. The microbes, for example, make
many “metabolites,” including different varieties of
fatty acids. That’s where Papin’s expertise in computer
modeling was critical. The models allowed the research team
to quickly determine which metabolites might be the most
important for biological timekeeping. That provided vital
direction for the work – and offers a valuable tool for
future research.
“Biology is increasingly a
data-rich science and computational methods are becoming
necessary to understand what the data tell us about
microbial and human physiological systems. Systems modeling
can help us embrace the complexity of these biological
systems to answer questions we have and to help us frame new
questions we didn’t even know to ask,” said Papin, who is
part of UVA’s Department of Biomedical Engineering, a
collaboration of UVA’s School of Medicine and School of
Engineering. “The future is very bright in biomedical
research as we take advantage of the data science and
computational methods being developed.”
By better
understanding the function of various metabolites, doctors
will be positioned to manipulate them to benefit good health
and improve quality of life. Tweaking the body’s
biological clock might benefit night-shift workers, for
example, or might be used to help patients fend off
Salmonella infections that cause food poisoning, as
Salmonella’s ability to invade the body is determined, in
part, by the circadian clock.
“Timing is
everything,” Moore said. “Understanding how the microbes
within us shape biological rhythms in the gut will
ultimately help us choose the right treatment, for the right
patient, at the right time.”
Findings
Published
The researchers have published
their findings in the journal Gastroenterology. The team
consisted of Fawad, Luzader, Hanson, Moutinho, McKinney,
Paul G. Mitchell, Kathleen Brown-Steinke, Ajay Kumar, Miri
Park, Suengwon Lee, David T. Bolick, Medlock, Jesse Y. Zhao,
Andrew E. Rosselot, C. James Chou, Emily Eshleman, Theresa
Alenghat, Christian I. Hong, Papin and Moore.
The work
was supported by the National Institutes of Health, grants
R01 DK117005, U19 AI116491 and R01 AT010253; UVA’s
TransUniversity Microbiome Initiative; and the National
Research Foundation of Korea, grant
2020R1A6A3A03038405.
To keep up with the latest
medical research news from UVA, subscribe to the Making
of Medicine blog at http://makingofmedicine.virginia.edu.
© Scoop Media
[ad_2]
Source link