A refined microbiome 'fingerprint' method tracks sub-strain variants of
a single gut microbe strain
An absence of sub-strain variation over a short period was seen in sick patients, which may signal impending gut dysbiosis

Date:
April 27, 2022
Source:
University of Alabama at Birmingham
Summary:
A previously developed a microbiome 'fingerprint' method that
identifies single strains of particular gut bacteria through
analysis of metagenomics data from fecal samples, has been
refined to include looking for single-nucleotide variants in the
KEGG metabolic pathways of a particular strain. This magnified
analysis shows a short-term difference in sub-strain dynamics of
two Bacteroides species between healthy individuals and hospitalized
COVID-19 patients.



FULL STORY ========================================================================== Casey D. Morrow, Ph.D., and colleagues at the University of Alabama
at Birmingham previously developed a microbiome "fingerprint" method
called WSS that identifies single strains of particular gut bacteria,
through analysis of metagenomics data from fecal samples. They have
shown that particular strains in adults tend to remain stable over time,
unless perturbed by events like antibiotics or obesity surgery. They also
saw that a donor fecal transplant strain given to treat drug-resistant Clostridium difficile infections persisted in the recipient for as long
as two years after the transplant.


========================================================================== Morrow and Hyunmin Koo, Ph.D., refined the fingerprint method to include looking for single-nucleotide variants in KEGG metabolic pathways of a particular strain. These variants can identify sub-strains of a single
strain identified by WSS. To look at sub-strains of a Bacteroides vulgatus strain, for example, Morrow and Koo examined 23 different KEGG metabolic pathways present in that bacteria.

They have now applied this magnified analysis to monitor changes in
sub-strains over shorter periods of time, days or weeks, in two key gut bacteria -- B.

vulgatus and Bacteroides uniformis. Comparing a small number of healthy individuals and hospitalized COVID-19 patients, they see a difference
in sub- strain dynamics that they say foreshadows a slowing down of the intrinsic rates of strain variation in the sick patients. This slowing
could eventually lead to a dysbiosis in the microbial strain community
that may portend a shift in the dominant strains of the gut microbiome.

Both of the Bacteroides species are found in high abundance in the gut
flora, and they may be keystone species, organisms that help define an
entire ecosystem.

Koo and Morrow's study, "Early indicators of microbial strain dysbiosis
in the human gastrointestinal microbial community of certain healthy
humans and hospitalized COVID?19 patients," is published in the journal Scientific Reports.

Koo and Morrow first analyzed previously published metagenomics data
from 41 individuals sampled one year apart and 11 individuals sampled
90 days apart.

They looked at a single dominant strain of B. vulgatus in each individual
at the two time points to see if they had showed different KEGG metabolic
sub- strain patterns, as detected from analysis of single-nucleotide
variants in KEGG metabolic pathways, or PKS. In general, most showed
a different sub-strain PKS pattern between the two time points of each individual.



==========================================================================
The UAB researchers then analyzed previously published metagenomics data
from six healthy individuals sampled every few days over three to 10
weeks, again analyzing sub-strains by single-nucleotide variants in 23
KEGG metabolic pathways. Three individuals showed a different sub-strain
at every time point, while three showed sub-strains had PKS patterns
that appeared, disappeared and reappeared at different time points.

Shared PKS patterns were also seen in two of three hospitalized COVID-19 patients who were sampled multiple times.

"We suggest that gut microbial communities under stress, such as those
found in COVID-19 hospitalized patients, might be in a state indicating
the potential shift in which the dominant strain would be outcompeted by
a minor strain," Koo said. "Disruptions of the gut microbial community resulting from a strain variation might, in turn, alter the community
structure and impact the functions in metabolism and colonization
resistance." "One of the features of a complex biological system is
that, as it approaches a critical transition, there is a slowing down
of the intrinsic rates of change," Morrow said. "The system enters
a condition that is related to autocorrelation, where the patterns
would be repeated between time points. It is possible that the shared
KEGG metabolic pathway clusters represent a state of autocorrelation
in the gut microbial strain community that portends a strain change."
Support came from the Marnix E. Heersink School of Medicine at UAB.

Morrow is a professor emeritus of the UAB Department of Cell,
Developmental and Integrative Biology, and Koo is a bioinformatician in
the UAB Department of Genetics.

The KEGG database is an acronym for the Kyoto Encyclopedia of Genes
and Genomes.


========================================================================== Story Source: Materials provided by
University_of_Alabama_at_Birmingham. Original written by Jeff
Hansen. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Hyunmin Koo, Casey D. Morrow. Early indicators of microbial strain
dysbiosis in the human gastrointestinal microbial
community of certain healthy humans and hospitalized
COVID-19 patients. Scientific Reports, 2022; 12 (1) DOI:
10.1038/s41598-022-10472-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220427154104.htm

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