Transforming Blood Transfusions

Blood is essential. It carries the oxygen you breathe throughout your body and to your lungs, keeping you alive and invigorated. However, our body can only produce so much blood in a day, and when we undergo serious blood loss through car accidents, genetic disorders, or surgeries, we need to replenish our body’s blood supply. People around the world donate their blood to those who are in desperate need and each year, 4.5 million lives are saved thanks to blood donations.

The transfer of one person’s blood to another person’s body is called transfusion, and in the United States alone, someone needs a transfusion every two seconds1. Currently, blood transfusions are limited by the type of blood one has – and therefore needs. Blood has four major types: ‘A’, ‘B’, ‘AB’, and ‘O’, and each of these major types has two subtypes, positive or negative. This means there are a total of eight blood types: A+, A-, B+, B-, AB+, AB-, O+, O-. These types are determined by different molecules called antigens (you can think of them as tags or signs) on the outside of the blood cell (see image below, different blood types have different molecular patterns or “tags”). 

The four major blood types are defined by the antigens, or “tags”, on their surfaces. The “H” antigen of blood type “O” is the most common, and can be converted by enzymes to “A” or “B” antigens. If you don’t have “A” or “B” blood types, it is because you don’t have the enzymes that can convert antigen “H” to the other antigen types.

Blood transfusions are limited by these specific antigens (tags) because the antigens are recognized by a person’s immune system or, the body’s defense system. If you have blood type “B”, and now have blood type “A” in your body, due to a transfusion, your immune system will recognize that “A” is not part of your body, and will trigger an immune response which attacks and destroys the blood that has been transfused.

A group from the University of British Columbia in Canada identified a bacterium in the human stomach that can convert blood type ‘A’ to the universal donor type, ‘O’2. By screening thousands of microbes in our stomachs, the scientists identified a particular obligate anaerobe (can only survive when oxygen is not present), Flavonifractor plautii. Inside F. plautii, two enzymes were found to work together to change the molecules on the surface of red blood cells of blood type ‘A’ to molecules of blood type ‘O’.

But how can blood types be changed from one blood type to another? 

Below is a diagram of blood type ‘A’ and blood type ‘O’. They have some “tags” in common (the blue squares, orange circles, and grey diamonds), and some that differ (green pentagon). The enzymes in F. plautii are able to cut off the extra molecular tag of blood type ‘A’, which then leaves blood type ‘O’! First, the enzyme FpGalNAcDeAc changes the ‘A’ blood type molecules to a slightly different molecule, which can then be recognized and cut by the second enzyme, FpGalNase, leaving blood type ‘O’. Not only can these enzymes change blood type ‘A’ to ‘O’, but they can do it fairly efficiently, which could greatly increase the blood supply for transfusions. 

Blood Type “A” to Blood Type “O” Conversion Pathway. FpGalNAcDeAc enzyme recognizes the “A” antigen, and changes it to a different molecule. This new molecule is recognized and removed by FpGalNase, leaving only the “H” antigen which characterizes blood type “O”.

The group from British Columbia are not the first to try changing blood type3. A previous study converted blood type ‘B’ to blood type ‘O’, albeit very inefficiently. So inefficiently, in fact, that the conversion would never have practical use4

Since the enzymes from F. plautii are bacterial, and only small amounts of the enzymes are needed for conversion of blood type ‘A’ to blood type ‘O’, it could be possible to mass produce the enzymes to be able to transform large quantities of blood for transfusions, increasing blood supply for medical procedures and saving more lives.

Sources:

  1. https://www.redcrossblood.org/donate-blood/blood-types.html
  2. Rahfeld, P., Sim, L., Moon, H., Constantinescu, I., Morgan-Lang, C., Hallam, S. J., Kizhakkedathu, J. N., and Withers, S. G. (2019) An enzymatic pathway in the human gut microbiome that converts A to universal O type blood. Nat. Microbiol. 10.1038/s41564-019-0469-7
  3. Goldstein, J., Siviglia, G., Hurst, R., Lenny, L. & Reich, L. Group-B erythrocytes enzymatically converted to Group-O survive normally in A, B, and O individuals. Science 215, 168–170 (1982).
  4. Kruskall, M. S. et al. Transfusion to blood group A and O patients of group B RBCs that have been enzymatically converted to group O. Transfusion 40, 1290–1298 (2000).

Peer edited by Abigail Agoglia

How Your Gut Bacteria May Be Talking To Your Brain

Bacteria are a big part of who we are as humans. They live all over us, forming distinct communities, or microbiomes, on our skin, in our hair, in our mouths, and in our guts. We host these microbes, and increasingly we’re learning that in turn they have a profound effect on our health. This is particularly true when it comes to the gut microbiome, which has been linked to conditions like Crohn’s disease and Irritable Bowel Disease.

The idea that the bacteria making a home in our guts have a role in our intestinal health doesn’t seem that far-fetched, but for several years there have been intriguing suggestions that our gut bacteria may also have an influence on our mental health.   

This has lead to a lot of hype around the idea that our gut bacteria may be controlling our moods or appetites to further their own ends. Experiments in mice and small-scale human studies have shown correlations between mood disorders like anxiety and depression, and alterations in gut microbiome composition.

source: www.mattniederhuber.com/PublicImages/gutbrainaxis.jpg
The gut-brain axis is like a high-speed connection between your central nervous and digestive systems.

It’s long been known that there is an intimate connection between the gut and the brain. Often termed the gut-brain-axis, this connection is like an eight lane highway facilitating a constant exchange of chemical information between the central nervous system and your belly. Ever since it was discovered in the 1980’s that bacteria produce compounds that have significant similarity to human hormones like insulin, scientists have wondered if gut bacteria may influence our mental state by producing their own sets of chemical signals.  

But the field hasn’t quite gotten far enough to definitively say how exactly that process might be taking place. This problem is particularly challenging because of how hard it is to make observations in the human gut. How can we work out what gut bacteria are doing if we can’t directly see them?  

Now, recent work from a group in Belgium has made one of the first efforts to address this question and functionally characterize how bacteria might influence mental state.  

By comparing the gut microbial compositions  and quality of life scores among a cohort of 1,054 Belgians, the group was able to test if particular bacteria were correlated with different mental health markers. While this type of association study isn’t new,  what is most exciting about their work is that they have developed a method for characterizing the neuroactive potential of certain gut bacteria.

The group built what they call “gut-brain modules,” which are essentially groups of genes associated with the synthesis of compounds with potential to interact with the human nervous system. They constructed 56 such modules, all centered around a different neuroactive molecule, such as dopamine or serotonin.  

By applying this gut-brain module framework to the gut microbial makeups of patients diagnosed with depression, they were able to identify and verify a single gut-brain module correlated with higher scores for social functioning. This module is associated with metabolism of Dopamine, a neurotransmitter that has been linked to pleasure and depressive disorders.

While this study doesn’t go so far as to argue a causative role for gut microbes in mental health, it does demonstrate a feasible approach to studying the black box of the human gut and that we may be one step closer to  understanding the role microbiomes play in our health.

Peer edited by Gabrielle Dardis.

Follow us on social media and never miss an article: