Microbe/Host Genetic Interactions

Nuclear Receptor

Here's a brand new paper out of Duke University that shows for the first time how gut microbes directly can effect host cells which could lead to human disease. This strengthens my notion that we must maintain a healthy gut flora and avoid upsets that can lead to colonization by pathogenic microbes.

Microbiota regulate intestinal epithelial gene expression by suppressing  the transcription 1 factor  Hepatocyte nuclear factor 4 alpha (Davison et al., 2017).

Sure to get a collective *yawn* from most readers, and even researchers, this paper explores a phenomenon that many seem to ignore:

...the roles of nuclear receptors  in host responses remain poorly understood, and no previous study has defined the impact of microbiota on nuclear receptor DNA binding. Nuclear receptors are a metazoan innovation.

Until recently, it was not believed that microbes could interact with their host more than superficially. A top cancer researcher once told me, "microbes are ubiquitous in nature...there's no way they can cause cancer." This Duke paper maybe proves him wrong! My contention has been all along that if microbes do interact with us on a cellular and genetic (DNA) level, then we must have also evolved ways to regulate this interaction so that we can live in harmony with the trillions of bacteria that inhabit us.

There's been evidence for decades that bacteria and fungi ("microbes") can cause cellular damage and genetic defects leading to disease, but little is known about the mechanisms involved. 

Nuclear Receptors

Nuclear receptors are an interesting area of molecular biology. Not many study them, it seems. And never before in the context of microbe/host interaction.

From Wikipedia:

In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules. In response, these receptors work with other proteins to regulate the expression of specific genes, thereby controlling the development, homeostasis, and metabolism of the organism.

If a hacker was looking for a way past an animal's firewall, it need look no further than the nuclear receptors. From here, you could control nearly every aspect of its host's life. The picture at the top shows a diagram of a nuclear receptor...it's a protein that binds to DNA and causes genetic changes. To go much deeper would entirely tax my day (and brain), but this is all the basis for what you hear described as "epigentics" and requires terms like "ligand" and "transcription factors." I'll spare us both the agony of a lesson.

The Duke Paper

This research demonstrates that certain host genes, in this case HNF4A of the Zebrafish, interact with genes of a microbe in the fish's intestine. If the researchers took away the HNF4A, the fish developed intestinal dysbiosis similar to that seen in human's with inflammatory bowel diseases.

The genes here are not important. The Zebrafish is not important. What is important is that here they are showing a direct mechanism whereby microbes interact with a host's DNA and cause alterations. It also shows that animals have developed defenses against these attacks.

Between the Lines

Reading between the lines, we do not see the names of any specific gut microbe named. We do not even see a differentiation between "bacteria" and "fungi" in the descriptions of gut microbes. These researchers have not identified the microbe that interacts with the host to cause disease. It's possible that there are many.

Another paper recently showed that human inflammatory bowel disease was more likely caused by the lack of gut bacteria responsible for digesting human bile. If this proves to be the case, it means we have been looking completely in the wrong direction for a probiotic treatment for certain bowel disorders. Instead of increasing bifidobacteria or whatever, we should be increasing the gut microbes that degrade bile, though there are virtually no papers describing these microbes.

Takeway

We do not know everything there is to know about gut microbes and how they effect our health. I think it's safe to say that we are up against a formidable enemy, these fungi and bacteria that inhabit us. But we are equipped with ways of dealing with them, making them work for us, even.  Until everything is known, I believe our best bet is to eat a diet filled with lots of plant fiber and whole foods. We should avoid unnecessary antibiotics and drugs. Live a healthy lifestyle. Let our food and our biology take care of us the way nature intended.

How do you know if its working?  What's your gut tell you?  Is it constantly upset?  Do you have a hard time "going?" Are you on meds for gut problems?  Do you have other health problems?  If you can answer "no" to these questions, then you are on the right track. If you answered "yes," then you have some work to do.

And keep in mind...this is not just a "gut thing." It's also about autoimmune diseases, cancer, and brain disorders. Most of the pharmaceuticals being developed for human diseases like these target the host immune system. You can do the same at home by eating right and exercising. But once these diseases get hold in you, all bets are off. So pay particular attention to what your gut is telling you, and keep your firewall updated!

Later!
Tim