Vitamin Riboswitches

Ever wonder whether there is a better way to understand and approach the use of vitamin supplementation for better health.

Do we really need all the vitamins that is available in multivitamin pill?

Is it easier to buy and take multi-vitamin supplements with the knowledge that others have most likely done the heavy lifting of science to create the product?

OR- Is there a better way to figure out the vitamin supplements that we need for our health – precision medicine of sorts.

The reality is although vitamins are important for human health, they most likely play a much bigger role (and have significant impact) on the bugs that live within us.  This is supported by science, though the specifics on the vitamin influence on bug health and its connection to our health is still a work in progress.  However, there is sufficient information to help navigate the connection between certain vitamins, their influence on the microbiome and impact on human health.

So, why are vitamins critically important for the bugs that are in our gut (microbiome)?  The answer to this question lies in the genetic makeup of the bugs and most likely part of our evolutionary dependence on external sources for food and nutrients to sustain life and health.

Vitamins are micronutrients that the body cannot make but still is required in sufficient quantities to use for various functions such as DNA & protein synthesis, energy production, immune function and overall health.  We typically get vitamins from food and supplements.  The general assumption is that vitamin supplements are readily accessed by the body and used as needed for maintenance of our health. The critical link of vitamins to the microbiome and human utility is part of the microbiome genetic makeup known as “riboswitches”.

What Exactly is a Riboswitch?

Think of a riboswitch as a smart thermostat for the bugs that are in the gut. Just as a thermostat detects temperature and turns heating or cooling on and off, a riboswitch detects specific molecules (like vitamins) and changes how genes work. These microscopic molecular managers sit right on the RNA – the messenger that carries genetic instructions for the bug to make proteins and get them to function properly.

How Do Riboswitches Work?

When a specific molecule – say, a vitamin – comes near a riboswitch, something remarkable happens. The riboswitch changes its shape, kind of like a key fitting into a lock. This shape change can:

  • Turn a gene on

  • Turn a gene off

  • Adjust how much of a protein gets made

Vitamins and Riboswitches: A Perfect Partnership

Many vitamins play a crucial role in activating riboswitches. Here are some cool examples:

Vitamin B12: The Activation Expert

Vitamin B12 is like a master key for certain riboswitches. When B12 is detected, it can:

  • Help bacteria adapt to their environment

  • Control important metabolic processes

  • Regulate how genes related to B12 metabolism are expressed

Thiamine (Vitamin B1): The Energy Regulator

Riboswitches linked to thiamine help cells:

  • Manage energy production

  • Adjust metabolism

  • Respond to changes in vitamin availability

Why Should We Care?

Many companies (list with links below) provide comprehensive microbiome profiling by sequencing the genes of bugs from feces.  This provides a good measure of individual gut health, information for which is provided by the companies so one can take steps to improve their gut and overall health.  Since vitamins have significant influence on microbiome health, the measurement of vitamins, metal co-factors and other chemicals known to influence riboswitches provides opportunity for individuals to monitor and adjust vitamin supplementation for optimal health.

Fun Fact

Riboswitches were only discovered in 2002, making them a relatively new and exciting area of scientific research. There is a lot more to be discovered in the near future.

Disclaimer

While this is exciting science, always consult healthcare professionals about your specific nutritional needs. Vitamins are important, but they're not one-size-fits-all!

Companies Providing Microbiome Profiling (list provided for information purposes only)

References (for scientifically inclined for deep dive into microbiome & health)

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  • Chauvier A, Walter NG. Beyond ligand binding: Single molecule observation reveals how riboswitches integrate multiple signals to balance bacterial gene regulation. Curr Opin Struct Biol. 2024 Oct;88:102893. doi: 10.1016/j.sbi.2024.102893. Epub 2024 Jul 26. PMID: 39067113.

  • Olenginski LT, Spradlin SF, Batey RT. Flipping the script: Understanding riboswitches from an alternative perspective. J Biol Chem. 2024 Mar;300(3):105730. doi: 10.1016/j.jbc.2024.105730. Epub 2024 Feb 8. PMID: 38336293; PMCID: PMC10907184.

  • Pavlova N, Traykovska M, Penchovsky R. Targeting FMN, TPP, SAM-I, and glmS Riboswitches with Chimeric Antisense Oligonucleotides for Completely Rational Antibacterial Drug Development. Antibiotics (Basel). 2023 Nov 8;12(11):1607. doi: 10.3390/antibiotics12111607. PMID: 37998809; PMCID: PMC10668854.

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  • Breaker RR. Riboswitches: from ancient gene-control systems to modern drug targets. Future Microbiol. 2009 Sep;4(7):771-3. doi: 10.2217/fmb.09.46. PMID: 19722830; PMCID: PMC5340290.

  • McCown, P. J., Corbino, K. A., Stav, S., Sherlock, M. E., & Breaker, R. R. (2017). Riboswitch diversity and distribution. Rna, 23(7), 995-1011.

  • Breaker, R. R. (2022). The biochemical landscape of riboswitch ligands.  Biochemistry. 61(3), 137-149.

  • Kavita, K., & Breaker, R. R. (2023). Discovering riboswitches: the past and the future. Trends in biochemical sciences, 48(2), 119-141.

  • Quarta, G., & Schlick, T. (2024). Riboswitch Distribution in the Human Gut Microbiome Reveals Common Metabolite Pathways. The Journal of Physical Chemistry B, 128(18), 4336-4343.

  • Mohsen, M. G., & Breaker, R. R. (2024). Prospects for Riboswitches in Drug Development. RNA as a Drug Target: The Next Frontier for Medicinal Chemistry, 203-226.

  • Kennedy KJ, Widner FJ, Sokolovskaya OM, Innocent LV, Procknow RR, Mok KC, Taga ME. Cobalamin Riboswitches Are Broadly Sensitive to Corrinoid Cofactors to Enable an Efficient Gene Regulatory Strategy. mBio. 2022 Oct 26;13(5):e0112122. doi: 10.1128/mbio.01121-22. Epub 2022 Aug 22. PMID: 35993747; PMCID: PMC9600662.

  • Donovan PD, Holland LM, Lombardi L, Coughlan AY, Higgins DG, et al. (2018) TPP riboswitch-dependent regulation of an ancient thiamin transporter in Candida. PLOS Genetics 14(5): e1007429. https://doi.org/10.1371/journal.pgen.1007429