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Comment by will_brown | Hacker News Reader

>Many diseases are as simple as your eyes being brown vs blue - you simply have or lack particular proteins.

I think the other half of this is the microbiome. I have been speaking to physicians about leaky gut recently and a great analogy is the protein genes are like a piano and the microbiome is like the musician.

As you suggest the genes/piano is sort of the hand you are dealt (you have the gene for certain disease or not), but the microbiome is what will typically unlock those diseases or not given the gene set. Another way of explaining this is that humans have about 20,000 genes, the most genes in any animal are about 35,000, and wheat has 164,000-334,000 genes. Obviously we are much more complex with the potential to carry many more diseases which physicians explained to m through humans having a microbiome.

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> the microbiome is what will typically unlock those diseases or not given the gene set

If true, that would be a Nobel-worthy finding. I don't think this is true, but do you have a citation supporting this for the "typical" genetic disease?

I’ve heard reports that changing out a microbiome has resulted in a few bald people regrowing their hair.

If you've "heard it", but you can't recall where, you should absolutely not believe your own claims. Either find the source again, or concede that you might have made it up. Because you are the easiest person to yourself to deceive into thinking something that isn't true.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290017/

https://www.nature.com/articles/nrg.2017.63

http://blogs.sciencemag.org/pipeline/archives/2017/09/13/wed...

Well I know without anyone reading or commenting on anything I link to I’ll be downvoted into oblivion for even trying to support conversations I’ve had with multiple physicians, still as a physician yourself I ask you to at least weigh in on the following...is it not true that while genetic mutations can be the sole cause of disease that most disease are triggered by a combination of genetics and environmental factors (i.e. not the same as a protein dictating whether you have brown or blue eyes)? To my point re the microbiome google points to multiple studies including but not limited to:

> Here are just some of the health conditions that involve our microbes: Acne Antibiotic-associated diarrhea Asthma/allergies Autism Autoimmune diseases Cancer Dental cavities Depression and anxiety Diabetes Eczema Gastric ulcers Hardening of the arteries Inflammatory bowel diseases Malnutrition Obesity

http://learn.genetics.utah.edu/content/microbiome/disease/

>Recent microbiome genome-wide association studies reveal that variants in many human genes involved in immunity and gut architecture are associated with an altered composition of the gut microbiome.

https://www.nature.com/articles/nrg.2017.63?WT.feed_name=sub...

>Researchers have discovered that a powerful guardian gene known to protect against a variety of autoimmune diseases, including type 1 diabetes, is triggered by the bacteria in our gut.

https://newatlas.com/guardian-gene-gut-bacteria-diabetes/511...

We can agree on many of the things that you wrote:

- You need a combination of genetics + environment to have a phenotype (whether disease or otherwise)

- Several conditions have a relationship with the gut microbiome

Also, I think you will enjoy this absolutely amazing study that found that the gut microbiome drives cerebral cavernous malformations(!!!) by interactions with TLR4: https://www.nature.com/articles/nature22075

So, I just don't think that "typically" the gut microbiome is the driver of disease. In fact, it's a rare enough find that people get Nature papers out of it. But, if it is actually typical, then I stand by my assertion that someone will eventually get a Nobel prize from proving it.

"microbiome" therapies has been one of the hottest areas in biotech the last five or so years. some of the hype has died down, however. microbiome therapies work well in c. difficile infections and some other gut diseases. in this case, you give a patient a set of "good" microbes that fight the "bad" microbes (c. diff).

people are studying microbiome therapies for cancer, autoimmune disease, cns disease, etc, but its way too early to tell if any of it is real. there are many challenges: how do you ensure the microbes you administer stay in the body, colonize, and actually produce the molecules you want them to? how do you manage the risk that they interact with other microbe populations in ways that are impossible to predict accurately, but potentially very harmful? how do you manufacture these things in a consistent, high quality way? what is the regulatory path? how do you justify a huge risky r&d investment when you can't patent a microbe? not to mention the biology risk; the "microbiome thesis" sounds nice, but how confident are we that microbes can treat cancer, depression, parkinsons? right now, not very

I don't think that is far-fetched. The gut contains about 70% of the cells of your immune system.

I have a genetic disorder. Working on my gut health has gone a long way towards reversing my symptoms.

I don't talk about it as much as I used to because it was a constant shit show from people being completely dismissive, outright calling me crazy and asserting utterly illogical things in the name of their "scientific" bias, like "Your 13+ years of steady forward health progress in the face of your degenerative condition is merely wild coincidence and doesn't prove that you know anything at all. Stranger things have happened!"

Cuz, yeah.

People who see themselves as scientific and logical are very often not remotely objective. They just have college degrees or whatever to justify their ugly personal prejudices, and don't confuse them with the facts.

I don't think there is a relationship between your personal experience and the OP's claim that diseases, broadly, are typically mediated by the gut microbiome.

So explain to me how 70% of the body's immune cells being in the gut is unrelated to how diseases are typically mediated. Pretty please.

The gut contains 70% of immune cells because your gut is actually the main point of contact between your body and the external environment. The surface area of your gut is somewhere from 20x to 100x that of your skin.

One could just as well argue that because the immune system is so well developed and robust in the gut that it's the last place to look for dysfunction. Or one could argue that a 70% share of immune cells is rather low considering the relative ratio of environmentally-exposed surface area.

We could say all kinds of things if we're free to make unsubstantiated conjectures. But we really can't say anything of substance without context and evidence. The human organism is ridiculously complex and consistently defies intuition.

Thank you for taking my question seriously.

I don't agree, but I appreciate the expanded perspective.

The way I used to describe it was that your genes are like the blueprints for a house and what you eat is like local building materials. The blueprints may specify 2 bedrooms, one bathroom, but exactly how that will look will depend a lot on the vernacular architecture. Is it adobe brick because you live in the American Southwest? Is it made of blocks of ice because you are an Inuit? Etc.

So, different building materials have different strengths and weaknesses. This will significantly impact things like ceiling height and room size because what shapes the material supports will vary, depending on the material.

I'm sorry some people are reflexively downvoting. I hate it that so many people who imagine themselves to be scientific are so incredibly dismissive of stuff like this.

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