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Thiamine Acquisition Strategies Impact Metabolism and Competition in the Gut Microbe Bacteroides thetaiotaomicron.
Thiamine (vitamin B1) is an essential cofactor for all organisms. Humans primarily acquire thiamine through their diet, and thiamine deficiencies have adverse neurological effects. However, the role gut microbes play in modulating thiamine availability is poorly understood, and little is known about how thiamine impacts the stability of microbial gut communities. To investigate thiamine's role in the gut, we utilized the model gut microbe Bacteroides thetaiotaomicron. Transcriptome sequencing (RNA-seq) revealed a global downregulation of thiamine and amino acid biosynthesis, glycolysis, and purine metabolism when thiamine was present. Using genetic mutants with thiamine biosynthesis and transport locus mutations, we determined both systems were critical for growth in thiamine-deficient medium. The defect in the double transport mutant suggests an uncharacterized feedback mechanism between thiamine transport and biosynthesis in B. thetaiotaomicron. Mutant phenotypes were recapitulated during pairwise competitions, reinforcing the importance of encoding versatile thiamine acquisition mechanisms when thiamine concentrations are variable. In addition, liquid chromatography-mass spectrometry (LC-MS) analyses corroborate that exogenous thiamine levels affect the internal thiamine pool of B. thetaiotaomicron. Furthermore, we computationally examined the ability of other gut microbes to acquire thiamine and identified lineage-specific differences in thiamine acquisition strategies. Among the Bacteroidetes, the capacities for both thiamine transport and biosynthesis are common. Together, these data show that thiamine acquisition mechanisms used by B. thetaiotaomicron not only are critical for its physiology and fitness but also provide the opportunity to model how other gut microbes may respond to the shifting availability of thiamine in the gut. IMPORTANCE Variation in the ability of gut microbes to transport, synthesize, and compete for vitamin B1 (thiamine) is expected to impact the structure and stability of the microbiota, and ultimately this variation may have both direct and indirect effects on human health. Our study identifies the diverse strategies employed by gut Bacteroidetes to acquire thiamine. We demonstrate how the presence or absence of thiamine biosynthesis or transport dramatically affects the abundance of B. thetaiotaomicron in a competitive environment. This study adds further evidence that altering the presence or concentrations of water-soluble vitamins such as thiamine may be an effective method for manipulating gut community composition. In turn, targeted thiamine delivery could be used therapeutically to alter dysbiotic communities linked to disease. Author Video: An author video summary of this article is available
Comment: Reflections of a Law Dean
https://scholarship.shu.edu/law_newspapers/1006/thumbnail.jp
The Dean\u27s Letter
https://scholarship.shu.edu/law_newspapers/1007/thumbnail.jp
PADAMOT : project overview report
Background and relevance to radioactive waste management
International consensus confirms that placing radioactive wastes and spent nuclear fuel deep
underground in a geological repository is the generally preferred option for their long-term
management and disposal. This strategy provides a number of advantages compared to leaving it
on or near the Earth’s surface. These advantages come about because, for a well chosen site, the
geosphere can provide:
• a physical barrier that can negate or buffer against the effects of surface dominated natural
disruptive processes such as deep weathering, glaciation, river and marine erosion or
flooding, asteroid/comet impact and earthquake shaking etc.
• long and slow groundwater return pathways from the facility to the biosphere along which
retardation, dilution and dispersion processes may operate to reduce radionuclide
concentration in the groundwater.
• a stable, and benign geochemical environment to maximise the longevity of the engineered
barriers such as the waste containers and backfill in the facility.
• a natural radiation shield around the wastes.
• a mechanically stable environment in which the facility can be constructed and will
afterwards be protected.
• an environment which reduces the likelihood of the repository being disturbed by inadvertent
human intrusion such as land use changes, construction projects, drilling, quarrying and
mining etc.
• protection against the effects of deliberate human activities such as vandalism, terrorism and
war etc.
However, safety considerations for storing and disposing of long-lived radioactive wastes must
take into account various scenarios that might affect the ability of the geosphere to provide the
functionality listed above. Therefore, in order to provide confidence in the ability of a repository
to perform within the deep geological setting at a particular site, a demonstration of geosphere
“stability” needs to be made. Stability is defined here to be the capacity of a geological and
hydrogeological system to minimise the impact of external influences on the repository
environment, or at least to account for them in a manner that would allow their impacts to be
evaluated and accounted for in any safety assessments.
A repository should be sited where the deep geosphere is a stable host in which the engineered
containment can continue to perform according to design and in which the surrounding
hydrogeological, geomechanical and geochemical environment will continue to operate as a
natural barrier to radionuclide movement towards the biosphere. However, over the long periods
of time during which long-lived radioactive wastes will pose a hazard, environmental change at
the surface has the potential to disrupt the stability of the geosphere and therefore the causes of
environmental change and their potential consequences need to be evaluated.
As noted above, environmental change can include processes such as deep weathering,
glaciation, river and marine erosion. It can also lead to changes in groundwater boundary
conditions through alternating recharge/discharge relationships. One of the key drivers for
environmental change is climate variability. The question then arises, how can geosphere stability be assessed with respect to changes in climate? Key issues raised in connection with
this are:
• What evidence is there that 'going underground' eliminates the extreme conditions that
storage on the surface would be subjected to in the long term?
• How can the additional stability and safety of the deep geosphere be demonstrated with
evidence from the natural system?
As a corollary to this, the capacity of repository sites deep underground in stable rock masses to
mitigate potential impacts of future climate change on groundwater conditions therefore needs to
be tested and demonstrated. To date, generic scenarios for groundwater evolution relating to
climate change are currently weakly constrained by data and process understanding. Hence, the
possibility of site-specific changes of groundwater conditions in the future can only be assessed
and demonstrated by studying groundwater evolution in the past. Stability of groundwater
conditions in the past is an indication of future stability, though both the climatic and geological
contexts must be taken into account in making such an assertion
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