Researchers discover the microbiome's role in attacking cancerous tumors | Hacker News Reader

Researchers discover the microbiome's role in attacking cancerous tumors

sciencedaily.com

55 pointsLinuxBender22 comments

The paper Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy [1]:

> We found that intestinal B. pseudolongum modulated enhanced immunotherapy response through production of the metabolite inosine. Decreased gut barrier function induced by immunotherapy increased systemic translocation of inosine and activated anti-tumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required co-stimulation. Collectively, our study identifies a novel microbial metabolite-immune pathway that is activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.

[1] https://science.sciencemag.org/content/early/2020/08/12/scie...

The findings are very interesting - who would one learn of the foods to eat to create a positive gut bacteria environment?

To a good first approximation, this is the crux of Pollan's dictum: "Eat food. Mostly plants. Not too much."

There must be more to it.

That's why I started out by saying "to a good first approximation".

I don't see a lot of value in the kinds of "quantified-self" hyperoptimizations people always seem so anxious to go for around this. Maintaining a good, healthy diet certainly isn't enough for everyone, and of course I see why folks for whom that doesn't suffice go deeper. But if you're starting anywhere else but by investing in the habit of maintaining a good, healthy diet, I think you're starting in the wrong place.

My experience has been that it is truly astonishing how much benefit can be derived simply from the habit of eating well.

Completely agree, there is no point these days to go beyond basic regime of eating healthy, exercising healthy, sleeping well, have good relationships, not too stressful work and maybe few little personal extra things like meditation or similar mood setter.

Each of these can be broken down to 1-2 levels of more details, but it doesn't make sense to go deeper. Ie with food - lots of veggies, then bit of +-healthy everything, ideally BIO, tasty, eat more in first half of the day etc.

The number of people who can consistently manage all of those to a good level would be astonishingly small. But we all can try to cover as much as possible, and it will be good enough for most for good healthy life.

You can keep a journal of your wellbeing to establish a baseline and then start making changes to your diet. For example, adding a green smoothie (mostly leafy greens, some fruit and nuts) to my breakfast every day seems to have ameliorated my IBS after a month or so. I'm still trying to add more vegetables to my diet because it seems like it's actually physically difficult to eat more than an optimal amount of them.

But your personal experience is the most direct data you can gather about this complex topic. Beyond generalities, diet is more likely than not idiosyncratic to each individual.

I think you must be right about that.

For example, while I'm sure I would also enjoy such a smoothie every morning, the probably quite high oxalate content would almost certainly bring about a quick recurrence of the kidney stones which removing all added salt from my diet has relieved. So I won't do that!

Regarding vegetables, have you considered salads? The genre offers far more variety than I think many suspect, and I don't know a more pleasant or more effective way of eating a vegetable-first diet than to get really good at salad.

Oh good call on the oxalate content! I'll be on the look out for that now, though it seems that I've been using low oxalate varieties of kale by preference.

I've been having a salad either as a whole meal or as a side every day as well. I still think I would benefit from eating more vegetables but only experiment and observation will tell.

I mean, you probably don't have to worry too hard about oxalates! The strongest predictor by far for stone forming is a history of stone forming, so I have to be very careful to limit oxalate-rich foods, but unless you've had problems before, you're likely good - although it's still not a bad idea to keep it in mind, because kidney stones suck a lot to have. And be sure to drink plenty of water, of course, but that's a good rule no matter what.

Another way I like to use vegetables is in sauces. It doesn't take much - what I'll usually do is start with a Béchamel (blond roux, add milk or cream) and then once it's well combined add handfuls of well-chopped onion, bell pepper, mushroom, or almost anything else I have on hand. Simmer and stir over low flame until the flavor and texture say "done". If you like spicy, then adding one whole finely minced habanero early on makes for a pleasantly gentle and slow-working heat; if you like umami, a generous dose of gorgonzola or some other strong cheese gives the sauce a unique base note. The juices from the vegetables (especially mushrooms, which are full of water) will join the sauce, bringing their volatiles along, and you end up with a subtle flavor that, depending on what you put in, will complement just about anything.

(If you eat meat and like steak, do be sure also to try it under a mushroom-and-gorgonzola sauce on this base! "That's got to be way too much" of both is about enough, and you can also add fresh crumbled bacon. Done right, it beats out any steakhouse I've ever been to. Enjoy!)

Consistently eat different kinds of plant fibers.

If you only eat the same thing, you'll lose diversity in your microbiota. Though we don't know yet which strains are "good" or "bad" (it's context-dependent), having diversity makes sure that all niches are filled and an usurper won't come in and cause problems.

This paper may help you, but it was done in germ free colonized with human microbiotas, so the results may not directly translate to humans:

Interspecies Competition Impacts Targeted Manipulation of Human Gut Bacteria by Fiber-Derived Glycans https://www.cell.com/cell/fulltext/S0092-8674(19)30899-2

Research shows that the best thing you can do is not be born and living in the industrialized world. https://www.nature.com/articles/d41586-020-00193-3

Very cool how we are learning that the microbiome seems to play a significant role in -so- many previously unexpected bodily processes.

Does anyone know of some other interesting findings to share?

There's a long and fascinating story about cancer as a metabolic disease. Turns 98% of modern cancer research on it's head.

I wish I could give a 200 word summary, but that would not do justice to the decades of research behind this approach.

Instead, I direct you to a book that could well save your life or the life of your friends and family: Tripping Over the Truth: The Metabolic Theory of Cancer[0]

[0]: https://www.goodreads.com/book/show/23496164-tripping-over-t...

For comparison, what kinds of diseases are not metabolic?

I'm not an expert in any means. I'm a software developer who has had some friends died of cancer, and then two years ago I read "Tripping over the Truth" and felt a sense of rage.

To take a stab at your question, at least in the context of cancer, cancer is almost never seen as a "cell metabolism" problem, it's viewed as a "damaged DNA" problem

Quoting from an article[0] that discusses the somatic vs. metabolic theories of cancer. This is how the "somatic theory of cancer" describes the cancer pathways:

> Cancer is caused by damage to DNA, which leads to damaged genes. Those genes, oncogenes, are responsible for the reproduction of cancer cell lines (which one could think of as multi-generation families), which grow unchecked to the point of being a tumor. Those tumors can be tested for damaged genes and will allegedly show those genes.

[0]: https://colleenhuber.com/metabolic-theory-of-cancer-and-comm...

As a cancer biologist, separating the metabolic from the somatic causes is complicated. Yes, ultimately cancers arise from the replication of cells with mutations in their DNA. But our immune system is on constant lookout for such cells and kill them once identified. So in a sense cancer is a failure of the immune system, and many things can depress the immune system, including metabolism.

I appreciate your response! I'm a layperson, so I am the last person qualified to give an informed response to your comment.

That said, I perceive a conceptual gap between your response, and my understanding of the metabolic theory of cancer.

I believe this gap exists because the 'metabolism' piece refers not to human metabolism, but cellular metabolism, specifically how mitochondria create energy.

I would be thrilled and honored if you'd read "Tripping Over the Truth"[0], but I know we all live in resource-constrained environments. You're not going to read a book because a random person on HN suggested it.

Because of this, and the fact that I dislike even hinting at "do unpaid labor", I am paying people to read this book.

I've allocated $5000 (5% of my pre-tax annual income when working, though I'm on a sabbatical right now) to getting certain well-positioned individuals to read Tripping Over the Truth[1].

Not to force or coerce anyone into agreeing with me, but I find the general theory to be so persuasive, I wonder if others might as well. I want expert insight into this topic.

Would you be willing to accept some of that "fund" and read the book? If, after reading, you'd be willing to give me a paragraph of your commentary on the book, I'd be eternally grateful.

I'd pay you $500 to read the book. If $500 isn't compelling, how about $1000? I'd send half when you agree to reading it, half when done (paypal, venmo, bitcoin, whatever).

I hope you're interested. My email is in my profile!

[0]: https://www.goodreads.com/book/show/23496164-tripping-over-t...

[1]: https://josh.works/mike-clayville-can-have-a-huge-impact-on-...

Did you have a look at this article?

"Here we show that metabolic alterations that occur with age can produce a systemic environment that favours the progression and aggressiveness of tumours."

https://www.nature.com/articles/s41586-020-2630-0

Genetic diseases, those caused by random mutations ie due to exposure to various radiation, and probably tons more.

Even those eating very healthy do get ie cancer, just less than average.

I'm hopeful we can look back on our primitive cancer fighting days when we simply take a booster shot for what ails us and we go back to work.

Fast track this

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