Gut microbes eat medication | Hacker News Reader

Gut microbes eat medication

chemistry.harvard.edu

185 pointsconse_lad52 comments

The more we know about the microbiome of the gut the more interesting its interaction with our health becomes. This is an example of a bacterium that eats L-dopa (a drug used to treat Parkinson's disease). There are a number of PhD's waiting to be handed out for additional research here I think.

I think there are Nobel prizes for more work here. We know so little about how bacteria affects our bodies and the true roles that they place, despite there being billions and billions of them.

I’m pretty sure if we aren’t careful the same replication crisis that happened in social science will happen here, the interaction of the gut bacteria is so complex it will be very difficult to get consistent results.

I wonder how far away we are from simulating the human gut, so we can introduce a variable, hit 'run', and take a snapshot every x hours.

I'm guessing we're 0.0000001% of the way there, given how complex all the interactions must be.

I work in a lab where some of the researchers are working on the much simpler fly gut. Even in the simpler fly It’s very difficult to get anything approaching causality because they’re are so many variables in gut bacteria populations. It’s a huge ecosystem unto itself.

Flies can eat literal garbage so I am also curious how their guts do not have arbitrary digestive problems (let's just say there's not much quality control on the input). Also whether they develop infections.

I looked around a teeny bit and there's some stuff but what you describe doesn't show up right away.

This is a chemical (?) simulator that's been around since 1993 I believe: https://www.wur.nl/en/product/Simulator-of-Human-Intestinal-...

I also found this numeric simulator: https://learn.genetics.utah.edu/content/microbiome/simulator... but I can't view the content right now.

They already do this to design fighter jets, rockets and space suits.

Those are much, much simpler systems. Your average human microbiome has 30+ trillion cells in it, too say nothing of the intestinal cells. That's not getting into the underlying complexity of the cells themselves.

I think we're still far away from that, but we're trying to get there. Some successful work has been done based on AGORA models [1], where the simulations seem to roughly match the reality of simplified systems. For example, for a five-member community of bacteria, answering questions like "what happens if we remove bacteria B from the community?", but not too much beyond that yet.

[1] https://www.nature.com/articles/nbt.3703

Having lost my own father to Parkinson's Disease (PD), my mother-in-law to a different progressive neurological disease and now watching my father-in-law walk through PD as well, your comment caught my attention. So I wondered if clinicians are doing fecal transplants to restore function in PD patients? A bit of searching and scanning found the following review

Gut microbiota: Implications in Parkinson's disease Parashar, Arun et al. Parkinsonism & Related Disorders, Volume 38, 1 - 7 [1]

Key passage

"This autonomic input from the gut is connected to the limbic system of the brain, which includes the hippocampus, the amygdala, and the limbic cortex. Limbic cortex is of importance since it regulates motor functions, which are impaired in PD. The connection between the limbic system and ANS is a critical factor underlying between gut health and brain & behavior [77]. Recently, it was found that fecal transplant from PD patients exacerbated motor impairment with reduction in Lachnospiraceae and Ruminococceae in recipient mice model of PD. Interestingly, same genera were significantly reduced in fecal samples from PD patients [27] link below [2].

Several case reports of patients with PD, multiple sclerosis, myoclonus dystonia, Alzheimer's disease, chronic fatigue syndrome, and autism have shown that FMT and/or antibiotic regimen was helpful in treating GIT symptoms like constipation, ulcerative colitis, and bowel disorders. Further, the therapy was helpful in relieving several non-GIT symptoms too"

[1]https://www.prd-journal.com/article/S1353-8020(17)30036-6/fu...

[2] https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.26307

I wonder how many diseases are becoming more prevalent because we eat manufactured food on a long term basis. Additives have been approved on the ground that they are not harmful to our body, yet we know very little in which ways they may influence our gut microbes (e.g. [1]).

A higher proportion of North Americans tend to find certain kinds of food/snacks from other cultures gross, yet the perfectly sterilized/packaged/high-sugar food options here are probably much more harmful.

https://www.sciencedaily.com/releases/2018/10/181001101932.h...

Not only is this a period of great extinction, this is also a period of great sterilization where we are trying to kill everything that eats anything that we produce... as if we are not one of those things and somehow separate from it all. In the end this war will either be won in which case we will probably have a number of other health issues to deal with or lost in which we recognize that there is no difference between us and the environment and that we are both part of a whole that we can shape immensely.

For a visceral encounter with extremes on this theme, read Kim Stanley Robinson's novel "Aurora".

The only way I see this being done is by running computer simulations. Knowing how complex our gut is, I'd say this can easily take another 100 years or so to get to the point where we can understand it in full.

Huh? Just survey people’s microbiomes, run cultures and use the drugs in the feedstock.

A number of human microbes aren't culturable yet.

I guess you do an in vivo post hoc analysis then.

In vivo bacterial population data isn't all that accessible yet either. Faecal bacterial samples have turned out to be poor representatives of the gut microbiome, so in vivo sampling requires endoscopy.

Fwiw, there are multiple biomes to sample too, with different types of bacteria lining the intestinal walls and other kinds populating the crypts, for instance.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837114/

> “But this kind of microbial metabolism can also be detrimental,” said Maini Rekdal, a graduate student in the lab of Professor Emily Balskus and first-author on their new study published in Science. According to Maini Rekdal, gut microbes can chew up medications, too, often with hazardous side effects. “Maybe the drug is not going to reach its target in the body, maybe it’s going to be toxic all of a sudden, maybe it’s going to be less helpful,” Maini Rekdal said.

To be fair (to our "hosts"), gut microbes do us far more good than harm. Yet we continue to prescribe antibiotics like they're Pez candies, and hand sanitizer'ed our way to "germ-free" because that's what sold the product.

Yeah but you don't get gut microbiota by eating with dirty hands, quite the contrary, a severe gastric infection can mess with your gut flora

Our concept of "dirty" needs revisiting.

What is the actual chance of getting the infection you describe? And in what conditions?

I wonder if there's actually something to the Raw Foodism movement, not because of their nonsense claims about enzymes, but because raw food contains more viable bacteria.

I've thought similar about microwaves. That is, using them to cook kills microbes - bad ones, but also good ones.

How does a microwave kill microbes more effectively than any other cooking method?

Microwaves. Not the same as gas heat, transfering thought a pan and into the food.

Time. A thorough X seconds in the microwave is more convenient than standing at the stove.

It's the tools. It's how they're most likely used.

If anything I'd expect microwaves' shorter cooking times and lower max temperatures to leave more bacteria alive.

They also don't cook evenly. You can have a TV dinner that is half molten and half frozen if you nuke it without the plastic lid.

Microwave sterilizers depend on steam to sterilize, not radiation. They just get the water to that temperature quicker than boiling in a pot.

Results also vary by organism being eradicated. Hamster in a microwave will end sadly. Cockroaches and ants will survive. Insects have less fatty tissue to absorb radiation I believe. Bacteria has none, so you do the math.

Uneven cooking is because of standing waves within the microwave. Lots of microwaves have rotating platforms to reduce this problem. If they're not being forcibly rotated, small enough creatures can avoid being cooked by staying at the nodes of the standing waves.

It is more complex. It's more about the environment that is created. Raw foods breakdown slower feeding different types of bacteria they have more bacteria but the live ones should be dead after stomach acid.

There was an article here recently about fatty acids in soil that reduce anxiety. Very interesting.

I am going all in on eating strawberries straight from the garden this year. Hasn't hurt in the past, & I know we're not using manure, so I figure it's good. Would love to see some research on this. Carrots from the yard with just a good scrub to get sand off: a microbiotic delight, or what?

If that were the case people would be falling over in masses on the regular. We evolved in a dirt-centric environment. The concept of clean and healthy is essentially a 20th-century invention. How's the working out of us.

Put another way, you might be correct but your analysis is the rare exception and not at all the rule. It's foolish to build ideals and behaviors around outliers.

It's working out really, really, really well for us.

We prevent an enormous amount of death and disease, very cheaply, with hygiene.

This right here. It's easy to talk about optimizing gut bacteria when people aren't dying in the streets of cholera. Not saying we haven't swung too far in the other direction, but we've solved some very big problems with water treatment and hand washing.

This is true but I assume that only a small minority of bacteria (and viruses?) have a negative effect on humans.

I can't refute the statistical point, but even if it is a small minority, the ones that do have a negative effect can be catastrophic. A vanishingly small percentage of wild animal bites transmit rabies, but we still treat the bites seriously with a vaccine because the consequences of being wrong are much worse than the consequences of a false positive.

But you do. That gut bacteria doesn't grow in a vacuum; it has to be introduced. Refusing to eat with shit-hands doesn't save you from possibly requiring a fecal transplant later to compensate for our social constructs.

That said, for the sake of invitation to any future dinner parties I do wash my hands, but while also understanding that if we were meant to be chemically "pure" then antibiotics would not destroy our guts just the same as that gastric infection.

Your initial gut bacteria "infection" most likely comes from your mother (through a couple of possible means), though there seems to be some scientific questions about that.

Otherwise, while you could get good bacteria from the environment, you'll also highly likely to get some bad pathogens as well, especially in urban environments. Or even worse, helminthic infections.

You could have fecal transplant candidates try several unwashed food sources and see what happens.

Medical inertia. Role of gut microbiome is only a recent trend. Soon we'll probably see change in nutrition and medical advices.

It appears to me that this may be an opportunity to harness the gut to intentionally deliver multi-stage options: perhaps relying on microbiome-consumption for timing and\or changing strategy mid-digestion?

To what would have been my great loss, I almost gave up on this article after reading the first three paragraphs. They set the stage for an agonizingly long article that would have made me work hard to glean meaningful insight. However, the rest of the article was somehow both consice enough for me to stay engaged, and descriptive enough for me to learn. (This is my humble plea to journalists to please forego this type of writing)

Not that it’s not an interesting workaround, but my reaction to hearing that L-dopa is poorly absorbed by mouth was to wonder if other routes had been tried[0]; seems simpler and more effective for those suffering with Parkinson’s.

[0]:https://www.ncbi.nlm.nih.gov/m/pubmed/28405912/

There's an inhaled form:

https://www.michaeljfox.org/news/inhaled-levodopa-time-moves...

IV will always be king for drug administration, but I'm not too surprised that it's oral absorption is poor considering amino acid absorption is fairly specialized within the GI tract.

“Why would bacteria adapt to use dopamine, which is typically associated with the brain?”

As we train ourself with instant hit of dopemine every 10 seconds using social media and other stuff, we have trained our microbes to do the same :)

I'm amazed that even chemotherapy drugs are consumed by gut microbes. I would assume it's only the pill form taken orally.

>The gut microbiota has the potential to directly metabolise chemotherapeutic drugs and also to modify the host metabolic milieu, indirectly altering host-chemotherapeutic metabolism

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145523/

Reading this, I cannot help but wonder.

We are clueless about the gut microbes in our body, but know a lot about dinosaurs. Most of the ocean floors remain inaccessible, yet we have a picture of the black hole. We have no idea where exactly are airplanes in the sky, but we are controlling rover on the surface of Mars that is sending us selfies.

I cannot help but wonder what if the Rover is actually on some unknown island on Earth itself & the picture of the black hole is actually something else.

FYI: I am just bored & hungry.

Is that the reason why it is advised against washing down pills with grapefruit juice? I know that it can cause overdose of the drug, but I'm not sure if it works by affecting those gut microbes or by blocking some digestive enzyme that normally destroys like 90% of drug's active substance before it can be absorbed.

Grapefruit interferes in a certain pathway in the liver. Some drugs are broken down in that pathway, so they stay longer in the body and build up, dose on dose, if you get too much grapefruit for too long. Other drugs are altered into their active form, or an intermediate; then, interfering with that keeps the drug from working at all. Furthermore, an intermediate form that is not supposed to last may be toxic, so you not only lose the dose, but get poison in its place.

It has lately become difficult to find grapefruit candy in the US. I wonder if there has been a public health directive from the FDA or someone.

After studying pharmacology and medicinal chemistry, I lost a lot of faith in our current pharmacological medicine.

The tl;dr is that chemistry is incredibly complex and then biology is even more complex and messy. Even if we think we understand the mechanism by which a medicine may work, we definitely do not know how something will certainly behave in the wider system OR whether something works the way we truly think it does (by the time a medicine arrives in the place it needs to be is it actually some chemical artifact after being "touched" so many times along the way).

We have a complex system, and we don't have the author or source code to hand, and we're still quite limited in how we can observe any changes. Any time we do try to introduce something we basically have to pray that there are no side effects

> After studying pharmacology and medicinal chemistry, I lost a lot of faith in our current pharmacological medicine.

My reaction was just the opposite. There are so many aspects of physics or other physical sciences that we take as basic knowledge and learn in grade school, but which were discovered years ago by some of the greatest thinkers of the past. It’s deceptively easy to wonder what it would have been like to live back then when the science was young and discoveries seemed more readily available. When you didn’t need to build a massive supercollider to validate theories. Of course much of this thinking is probably a fallacy... hundreds of years from now people will think similar thoughts about where we are.

And yet medicine quite clearly seems at this earlier stage. Think about how far we’ve come in just the last century... we’ve only known about antibiotics for 100 years and the structure of DNA for half that long. That’s not a reason to be dismissive, medicine right now is in its early days and the people doing the research are pioneers. Medicine today has so many opportunities for smart people to contribute.

Right and that's fine - I agree an optimistic way to look at medicine is that we have yet so much more to discover.

But I look at the massive pro-medicate industry that is incentivised to get us to take medicine which is built upon disappointingly unrigorous discipline and the confidence some doctors carry themselves on matters which really aren't as clear cut as they think and I kind of want to nope out of the system - I'd rather lean on my body to fix itself whenever I can.

(ironically the best doctors I know generally advise the same, the exception being all the obvious cases where medicine has successfully intervened)

Does this mean that people from Awakenings could have prolonged their state of being functional through intravenous delivery of l dopa?

Reply on news.ycombinator.com