We are, simply, chemical reactions

I have recently read this article and it was well discussed how scientists keep discovering new interesting and important facts about our gastrointestinal tract and its effect on our wellbeing (including decision making and brain function).

For example, it has been shown that if people eat more galactooligosaccharide, the fraction of bacteria Lactobacillus and Bifidobacteria in the gut increases among all other strains (because metabolism of these bacteria takes advantage of the excess of this chemical, a known prebiotic). At the same time, these particular strains of bacteria have been shown to produce certain neurotransmitters — chemicals that participate in our brain functioning (because neurotransmitters are responsible for the transmission of electrical signals between neurons). It is indeed possible that by eating certain types of food you can overproduce certain neurotransmitters and, therefore, influence your brain functioning — through bacteria in the gut (Figure 1).

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Figure 1. Feeding healthy volunteers with galactooligosaccharide resulted in the increased population of Lactobacillus and Bifidobacteria in the gut which, in turn, resulted in overproduction of neurotransmitters that affect anxiety, including one called brain-derived neurotrophic factor [1].

What is even cooler, some bacteria have shown to affect people’s mood (possibly, by increasing production of “happiness hormones”, in other words, chemicals responsible for our social behavior). This is reasonable because happy people are more social which leads to a big evolutionary advance for these bacteria: they would obviously tend to spread better between social humans than between loners. Interesting, isn’t it?

Let’s now think about it in an evolutionary context. Do bacteria in the gut understand that they change the social behavior of their hosts? The answer is – NO. They not only don’t know anything about social behavior, but they also don’t know that they have a host and even that they exist! Bacteria are simply self-sustaining chemical reactions capable of changing (mutating) their chemical dynamics. It is not that bacteria have goals to survive, they simply occur. One random mutation in their genome led to the overexpression of a random chemical which, by a myriad of other complicated chemical transformations led to the increase of a random neurotransmitter which, by accident, tended to affect social behavior of their hosts. Now, the bacteria have started to spread faster and still spread “happily” because these chemical dynamics help them to exist or, simply, to occur.

We, humans, are chemical reactions too. All hopes and dreams in our brains are interactions between atoms, molecules and their collections. We just tend to occur because it is evolutionary logical. Our mood is chemistry too: serotonin is happiness, dopamine is pleasure, noradrenaline is concentration (Figure 2).

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Figure 2. The structures of neurotransmitters and their common effects on the mood, concentration, and learning.

So, if all of this is chemistry, then how to study this? Are there techniques that would allow us to investigate gut microbiome and its effect on the brain non-invasively and in real time?

I believe the answer is yes. Non-invasive techniques like NMR and MRI will soon be able to help to answer important questions about gut metabolism with hyperpolarization being one of the main tools to achieve this. The main challenge – fast decay of polarization – will be overcome by using nuclear states that can preserve their “memory” on a timescale of hours. Remarkably, there are already reports on the long-lived hyperpolarized nuclear spin states [2-4]! Long-live the gut! 😉

 

 

[1] “When Gut Bacteria Change Brain Function” bDavid Kohn.

[2] https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201405063

[3] https://pubs.acs.org/doi/abs/10.1021/acs.jpclett.7b00987

[4] https://www.sciencedirect.com/science/article/abs/pii/S1090780717300216

My “Dream Research” Project

If I was asked to identify the most challenging biological question, I would answer immediately. What is the nature of memory and thought? This question always fascinated me as a child. For a long time, I thought only biologists can figure that out. It took me 10 years deeply studying physics and chemistry, becoming a specialist in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI), to realize that actually now we are close to start answering the question which captivated my childish mind.

 

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Metabolic Metro Map. The image is taken from Wikipedia.

 

With all its complexity, the end result of the genetic machinery is to affect the chemistry of the body. Small molecules, metabolites, serve as fingerprints of what is happening inside us. Studying metabolites is almost like looking at someone’s apartment and coming up with a story of their recent lives: we can make guesses about a lifestyle based on what we see! And the chemistry of thinking is not an exception – our thought processes are accompanied by myriads of chemical transformations, and leftover metabolites can tell us about the process behind them.

Studying metabolites is almost like looking at someone’s apartment and coming up with a story of their recent lives: we can make guesses about a lifestyle based on what we see!

Routinely, metabolites are measured through analytical techniques like NMR and mass spectrometry (MS). But a new astonishing era is emerging. With new sensitivity enhancement techniques (signals can be increased by more than 20,000 times [1-4]), MR imaging will become a new tool to study metabolism in vivo and will move beyond morphology onto a platform to visualize molecules. Being fundamentally a quantum mechanical technique, the full potential of MRI is yet to be discovered.

I see my “dream research” project as the development of a new experimental MRI-NMR/MS platform to study metabolomics of memory and thought in living creatures. By developing novel MRI pulse sequences (which will take into account quantum-mechanical nature of molecules) and by applying state-of-the-art signal enhancement techniques, we will be able to “light up” the regions of the brain to study chemistry in them with an unprecedented level of accuracy. I believe that once all new methodologies available today are combined, it will become possible to create functional MRI for metabolomics – a tool to study instant chemical changes in the brain associated with memory and thinking. This will not only revisit the known biochemical processes at a new quantitative level, it will allow unraveling unexpected secrets of metabolism. And it is not only a fun thing to do — understanding the biochemical reasons for making decisions will bring us much closer to a society in which everyone truly enjoys living.

 

[1] J. H. Ardenkjær-Larsen et al. Increase in signal-to-noise ratio of >10,000 times in liquid-state NMR. Proc. Nat. Acad. Sci., 2003, 100 (18), 10158-10163.

[2] R. W. Adams et al. Reversible Interactions with parahydrogen Enhance NMR Sensitivity by Polarization Transfer. Science, 2009, 323 (5922), 1708-1711.

[3] D. A. Barskiy et al. Over 20% 15N Hyperpolarization in Under One Minute for Metronidazole, an Antibiotic and Hypoxia Probe. J. Am. Chem. Soc., 2016, 138 (26), 8080–8083.

[4] D. A. Barskiy et al. NMR Hyperpolarization Techniques of Gases. Chem. Eur. J., 2017, 23 (4), 725-751.