Our Cancers are Filled with Fungi

October 2, 2022 9:56 AM

New research shows that many cancers play host to their own unique microbiomes of fungi, which may affect our chances of surviving them.
posted by tiny frying pan (44 comments total)

It's taken *this* long to spot fungi in Cancer tumors? wtf?

This reminds me of when they finally spotted that bacteria (H. Pylori?) that turns out to cause stomach ulcers after how many decades prescribing milk or "reduce stress" or... whatever.
posted by aleph at 10:06 AM on October 2, 2022 [10 favorites]

What is candida good for in the human body?
posted by aniola at 10:35 AM on October 2, 2022 [2 favorites]

Fascinating. Thanks, tiny frying pan! The study in Cell; press release; coverage at Nature: Furthermore, many of the fungal species in question are widespread, which makes sample contamination a serious concern, says [immunologist Iliyan] Iliev. That meant the researchers had to take great care to filter out any potential evidence of contamination or false matches for fungal DNA from their results. For example, Iliev and his colleagues found a DNA fragment misidentified as portobello mushroom (Agaricus bisporus), a common edible fungus, in tumour tissues from across the body.

Both research teams got most of their tissue and blood samples from databases, so the samples were not collected with the aim of minimizing fungal contamination, says [microbiome specialist Ami] Bhatt. Although the researchers developed methods to filter any potential contaminants out of the sequencing data, she would like to see the results replicated using samples taken in a sterile environment.
posted by Iris Gambol at 11:44 AM on October 2, 2022 [10 favorites]

I'm not terribly surprised that this is a new discovery, as it's just been a few years since human biologists discovered an entirely new organ in the human body.
posted by Halloween Jack at 11:45 AM on October 2, 2022 [9 favorites]

Fungi   Cancer cells
     🤝
"You cannot kill me in a way that matters"
posted by acb at 11:56 AM on October 2, 2022 [15 favorites]

I can still eat cheese, tho, right?
posted by symbioid at 12:02 PM on October 2, 2022 [1 favorite]

All cheese is edible. Some cheese is just edible for a limited time.
posted by acb at 12:06 PM on October 2, 2022 [2 favorites]

"...not terribly surprised that this is a new discovery"

They seem to be stumbling all over themselves with a new discovery every week about the role and connections the gut biota have with systems all over the body.

Not real surprising. This

"The era of fast, cheap genome sequencing is here"

We're just finally opening the box for a lot of this. Depressing really. I'll be dead before the benefits start making it out. Though I'll miss the horrors as well.
posted by aleph at 12:08 PM on October 2, 2022 [6 favorites]

about the role and connections the gut biota have with systems all over the body.

Whoops, it might be true generally, but I didn't mean to imply that about this article.

This team also found plenty of fungi nestled within human cancers, with some cancers being more likely to harbor certain fungi than others. In lung cancer tumors, for instance, Blastomyces fungi were more commonly found, while Candida fungi were more common in gastrointestinal cancers.

I just keep hearing about candida overgrowth, which implies there is a normal and acceptable amount of candida, which implies it's gotta be good for something. And then I thought that if we know what it's good for, maybe it can tell us something about things like this, like why it's found in GI cancers.
posted by aniola at 12:20 PM on October 2, 2022 [2 favorites]

I suddenly have a powerful urge to take huge doses of antifungals.
posted by aramaic at 12:39 PM on October 2, 2022 [3 favorites]

@aniola: Naah. I didn't get that implication from the article, or your post. Just my reaction to major discoveries popping up like this. Would have thought we'd have figured out the basics by now and surprises like this emphasis how we still haven't.
posted by aleph at 12:51 PM on October 2, 2022 [1 favorite]

@aramaic you might want to look into the side effects of azole drugs beforehand. Anaphylaxis and permanent liver damage, for example
posted by apathy at 1:16 PM on October 2, 2022 [5 favorites]

Until recently I had a small South American catfish in my aquarium with a massive tumour on its dorsal fin. The tumour would grow quite rapidly for about a year, and then would be attacked by a fungal infection. The fungal infection seemed to destroy almost all of the tumour, then the fish would recover and go back to normal life. And then the tumour would re-grow and the cycle would repeat. It survived that way for about seven years. It's just a random anecdote, but this brought it to mind.
posted by pipeski at 1:43 PM on October 2, 2022 [25 favorites]

One possible benefit of Candida in the microbiome: Candida reduces severity of C. difficile and P. aeruginosa infections in mice.
posted by Emmy Noether at 1:50 PM on October 2, 2022 [2 favorites]

Life is body horror.
posted by Ursula Hitler at 2:01 PM on October 2, 2022 [46 favorites]

Here's a similar article*, from which I'm inferring the thing to do might be to try to maintain a balanced immune system rather than wipe out your funguses. It sounds like there's some sort of predator/prey thing going on with the funguses and bacteria inside us. Even more so with that catfish story!

*I've been trying to remember to put content notes about whether or not a study involved animal experimentation, like Emmy Noether did above. I didn't notice any in this article, but I know at least one of the cited articles does.
posted by aniola at 2:25 PM on October 2, 2022 [3 favorites]

@acb Should viruses enter the chat?
posted by VyanSelei at 3:20 PM on October 2, 2022 [1 favorite]

Its nice to know my teratoma has taken up mushroom farming as a hobby.
posted by The Power Nap at 3:23 PM on October 2, 2022 [6 favorites]

You Cannot Kill Me In A Way That Matters
posted by lalochezia at 3:33 PM on October 2, 2022 [8 favorites]

What is candida good for in the human body?

Wouldn't surprise me now to learn that it's good for slowing the growth of certain kinds of tumour.
posted by flabdablet at 3:39 PM on October 2, 2022 [1 favorite]

Its nice to know my teratoma has taken up mushroom farming as a hobby.

WARNING. If you are thinking “huh, what’s a teratoma?” and considering doing a google search to find out, let me warn you first that sometimes the human body comes up with these completely FUCKED UP tumors called teratomas that contain, like, teeth and hair and other shit in completely inappropriate places - lungs! Reproductive organs! - and just think on that a minute before deciding whether you want to see pictures of it. FUCKING YIKES.
posted by obfuscation at 3:44 PM on October 2, 2022 [8 favorites]

And the worst are the fetiform teratomas, of which there are only about 20 recorded cases to date.
posted by jamjam at 4:04 PM on October 2, 2022 [1 favorite]

Jesus Christ human body get your shit together
posted by obfuscation at 4:18 PM on October 2, 2022 [13 favorites]

I had a teratoma! It was about the size of my palm and I think it had hair but sadly no eyes or teeth. I foolishly didn't ask for the pictures until later and my doctor no longer had them handy. If it had a mushroom farming hobby that wasn't brought to my attention.
posted by sepviva at 4:43 PM on October 2, 2022 [5 favorites]

Worth noting that the authors of the research paper are careful to stress that their results are only correlative, and they cannot infer any causation, either from fungal infection to cancer or vice versa. In biology, the answer is usually "all of the above," so a good first guess is that in some cancers, the fungal infection played a causal role, while in others, the fungal infection is opportunistic. The key question, of course, is which is more common.

Intuitively, it seems more parsimonious to think that most of these fungal infections are probably opportunistic, because cancerous tumors often involve immune suppression. The study found that many of these fungi are intracellular, meaning they colonize within the interior of the cancer cells. Cancer cells, as one of their primary characteristics, are able to elude the normal immune processes that detect sick/infected cells, so unlike otherwise healthy tissue, fungal infections in tumor cells would probably be safe from the immune system. Cancer cells also lose some of the mechanisms for detecting and responding when something goes wrong internally to themselves, providing another layer of safety to the infecting fungi. It's even possible that certain fungal infections could turn out to be beneficial, if they harm the cancer cells more than they harm non-cancerous tissue.

However, while the principle of parsimony is a good starting point for calibrating your expectations, it's only a starting point, and that doesn't rule out the possibility that fungal infections could play a causal role in some or many cancers. I'd say this study provides good motivation for further follow-ups to try to determine whether such a mechanism does exist, but no strong evidence so far to think that it would.

Regardless, one of the things that's pretty interesting in the study is the finding that different types of cancer have different complements of fungal species, what they term the "mycotype," and furthermore that the mycotype may correlate with clinical outcomes. That means that whether or not the fungi play any role in causing cancer, sequencing the mycotype of a tumor could turn out to be diagnostically useful.
posted by biogeo at 6:30 PM on October 2, 2022 [14 favorites]

Life is body horror.

David Cronenberg is furiously taking notes. "Fungus Among Us" will be released summer 2024.
posted by zardoz at 6:35 PM on October 2, 2022 [4 favorites]

It's even possible that certain fungal infections could turn out to be beneficial, if they harm the cancer cells more than they harm non-cancerous tissue.

This is what I was thinking, too. Complete with all your caveats. Caveat the following as needed: But the fungus would probably never want to kill off the cancer entirely, right? As seen with the catfish mentioned above? It sounds like that cancer is dinner! And shelter!
posted by aniola at 8:21 PM on October 2, 2022

One of the most carcinogenic classes of substances known happens to be produced by various subspecies of Aspergillus:

Aflatoxins are among the most carcinogenic substances known.[13] After entering the body, aflatoxins may be metabolized by the liver to a reactive epoxide intermediate or hydroxylated to become the less harmful aflatoxin M1.

Aflatoxin poisoning most commonly results from ingestion, but the most toxic aflatoxin compound, B1, can permeate through the skin.[14]

Some of those subspecies, such as Aspergillus parasiticus, are also known to infect people

2] In humans, exposure to A. parasiticus toxins can cause delayed development in children and produce serious liver diseases and/or hepatic carcinoma in adults.[3] The fungus can also cause the infection known as aspergillosis in humans and other animals. A. parasiticus is of agricultural importance due to its ability to cause disease in corn, peanut, and cottonseed.[2][4]

Causing developmental delay and also "stunted growth" seem unusual, but they would be understandable if the immune system was attacking the fast dividing cells of children which had been transformed into a cancerous or precancerous state by aflatoxins.

I think the fact that Aspergillus produces one of the most carcinogenic substances known supports the idea that fungi can live in cancers because otherwise the benefits to the fungus of inducing cancer would be much more indirect.
posted by jamjam at 9:27 PM on October 2, 2022 [1 favorite]

I’m sure this line of thinking is too reductive to be scientifically useful, but I’ve always thought of cancer as a kind of unchecked “death-curse” dwelling inside a body.

Not surprising that such a thing would harbor opportunist fungi.
posted by Doleful Creature at 9:59 PM on October 2, 2022 [1 favorite]

David Cronenberg is furiously taking notes.

Hyphae are the New Flesh!
posted by flabdablet at 10:31 PM on October 2, 2022

I think the fact that Aspergillus produces one of the most carcinogenic substances known supports the idea that fungi can live in cancers because otherwise the benefits to the fungus of inducing cancer would be much more indirect.

That seems to be a bit of a red herring for two reasons.

First, aflatoxins are activated by liver enzymes: most of the toxic effects occur specifically in the liver not because there are Aspergillus in the liver but because liver enzymes (specifically cytochrome P450s) process the secreted aflatoxin precursor that reaches the liver, and that forms the particularly nasty aflatoxin epoxides that do much of the damage. Liver enzymes aren't produced all over the body; I wouldn't necessarily expect much aflatoxin activation to happen in an Aspergillus infection that wasn't liver-localized (or in some other P450-rich environment.)

Second, unusual enrichment of Aspergillus in general and known aflatoxin producers specifically simply wasn't reported in these papers. There were genera commonly detected by both studies (and given the amount of variability one sees in microbiome studies, I'd put more weight on species and genera found in both studies.) But Aspergillus strains weren't actually notable ones. The study from Iliyan Iliev's group found Candida dominating gastrointestinal tumors, Blastomyces in lung tumors, and Malassezia in breast tumors. A second study from Ravid Straussman's group found mostly the same 3 genera - along with Streptomyces cerevisiae which you know well from bread and beer. There were a few other genera associated with other tumors - Cladosporium in breast cancer, Phaeosphaeria in ovarian cancer, etc. Aspergillus do get mentioned in the paper from the Straussman group, generally in similar contexts to Candida strains, but neither Aspergillus flavus nor Aspergillus parasiticus are mentioned (and given that other strains are identified at the species level (they did whole genome sequencing and were able to get coverage sufficient to ID a bunch of strains), and that they actually used some techniques targeted towards identifying Aspergillus strains, that absence seems potentially meaningful: it isn't that they weren't looking for Ascomycota, or for Aspergillus, or that they weren't able to detect any strains at the species level.) So at least in these studies, there doesn't seem to be anything to support this specific aflatoxin/Aspergillus-focused hypothesis.

More broadly, the fact that there exist fungal strains that produce carcinogens doesn't mean that those specific strains are actually members of tumor microbiome populations; the same can be said for bacterial strains that produce carcinogens. (Given how frequently carcinogens are secreted from microbes, there's not necessarily any need for a carcinogen-producing microbe to be anywhere near the final cancer location, and cancers generally require a cascade of multiple mutations: the carcinogen-producers can be long gone (or were never nearby to begin with) before enough mistakes accrue to turn a cell cancerous.) biogeo's point regarding parsimonious interpretations is a really important one - I'd certainly hazard a guess that S. cerevisiae shows up more because we're around a lot of it than because it's a major carcinogen producer. Along the same lines, I'll also note that different tumor environments might be associated with different metabolite profiles that different fungal strains are particularly well-placed to exploit. None of this rules out a more direct carcinogen connection (that goes for prokaryotes associated with tumor microbiomes too!) - more work is definitely merited! - but the data in these papers, at least, aren't sufficient to either show that there is any kind of direct carcinogen connection or rule it out.
posted by ASF Tod und Schwerkraft at 11:49 PM on October 2, 2022 [5 favorites]

See also this earlier FPP: Our warm-blooded natures - in brief: our warm-bloodedness helps protect us from fungal infections - if we were plants or reptiles then we would be much more scared of them. But fungi are still there waiting for an opportunity and cancel tumours may well give them that "in" they seek. Interesting.
posted by rongorongo at 1:49 AM on October 3, 2022 [1 favorite]

This reminds me of when they finally spotted that bacteria (H. Pylori?) that turns out to cause stomach ulcers after how many decades prescribing milk or "reduce stress" or... whatever.

Some stomach ulcers are caused by bacteria. Not all.
posted by srboisvert at 5:24 AM on October 3, 2022

aniola: It sounds like there's some sort of predator/prey thing going on with the funguses and bacteria inside us.

In David Brin & Gregory Benford's novel "Heart of the Comet," a crew burrows into Haley's Comet in order to mine it resources. A weird infection takes over, and the humans reorient to fighting the crud just to survive. (It's not as grody as it sounds.)

The story spins out over a long period of time, but even years after reading the book, I remember the descriptions of one scientist, Saul, who allows himself to be colonized by the comet's microbes as part of his research and ends up covered in weird growths that everyone just sort of accepts because they need him and it keeps him alive.
posted by wenestvedt at 6:47 AM on October 3, 2022 [2 favorites]

I’ve been reading up a bit on lichens, which as it turns out are actually algae and fungi in a symbiotic relationship that doesn’t resemble either the original algae or the original fungi… wonder if this could have any relation to that extremely trippy process.
posted by showbiz_liz at 7:25 AM on October 3, 2022 [2 favorites]

When I read "biome" I assumed bacteria and was surprised it turned out to be fungus. I'm still holding onto hope that there will also be bacteria.
posted by Nancy Lebovitz at 7:31 AM on October 3, 2022

I'm lichen your theory.
posted by aniola at 8:49 AM on October 3, 2022 [2 favorites]

> When I read "biome" I assumed bacteria and was surprised it turned out to be fungus. I'm still holding onto hope that there will also be bacteria.

You don't have to hold out any longer! The pop science reporting on this hasn't been great: it's not just fungi in tumor microbiomes. The presence of fungal strains was unexpected (and the tumor-specific correlations as well), and so these papers are getting a bunch of attention. But we already knew there were bacteria associated with tumors, though again the cause and effect of their presence and their tumor association is often still unclear. Here's the Straussman group two years ago on bacterial components of tumor microbiomes. Their current study actually explicitly discusses bacterial components of tumor microbiomes and makes it really clear that bacteria are by far the predominant microbes (and discusses how you also see some specific co-occurrence patterns between fungal and bacterial strains.) The takeaway from the current papers should be "huh, there are some fungal strains too?!" not "the tumor microbiome is composed of fungal strains."
posted by ASF Tod und Schwerkraft at 9:30 AM on October 3, 2022 [4 favorites]

@srboisvert:

"Some stomach ulcers are caused by bacteria. Not all."

Is there any consensus on how much of each?
posted by aleph at 10:10 AM on October 3, 2022

90%+ are caused by bacteria.
posted by Mitheral at 11:45 AM on October 3, 2022

I'm lichen your theory.

algaet you for that.
posted by flabdablet at 12:16 PM on October 3, 2022

@Mitheral
Thanks. Was my impression but didn't have data.

"It causes more than 90 percent of ulcers..."

It's amazing (to me) that this was unrecognized for so long.

"Before 1982, when this bacterium was discovered, spicy food, acid, stress and lifestyle were considered the major causes of ulcers."

I wonder if it suffered from bleed over from being partially thought of as a "mental" condition. Those tend to be ignored/minimized a lot.
posted by aleph at 2:26 PM on October 3, 2022

NSAIDs also cause ulcers.
posted by aniola at 5:43 PM on October 3, 2022

“…as aflatoxin metabolites may intercalate into DNA and alkylate the bases through epoxide moiety.”

Meanwhile, work has been proceeding on a chemical pathway that would canalize the interstitium using modial lysis, rather than through the interaction of franked exzymes and cross-boomed lipid walls; such a process is known as bioencabulation.
posted by sixswitch at 8:22 PM on October 3, 2022 [3 favorites]