Bacteria (and their metabolites) and depression | Hacker News Reader

Bacteria (and their metabolites) and depression

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I can’t go into too much detail here, but I interrupted a severe depression by fasting for two straight weeks. It’s hard to say why it worked — my friends assume that the microbiome is implicated because of the dietary change. Plausible, but hardly a proof. This gives me at least one direction to look in.

As an alternate theory, I’ve always thought that deliberate, controlled suffering gives you a mood boost. Or rather, the relief after the suffering has ended. The theory is that it’s not good for us emotionally to be comfortable continuously. Maybe fasting is an example of that?

That’s personality-specific. My Dad is like that and doesn’t understand why nobody else in the family gets off on self-imposed austerity. (He’s a great guy by the way — we all have our quirks.) He loves to say it’s a lack of discipline, but it’s not— I quit smoking after a decade-and-a-half of heavy smoking, lost 20% of my body weight on an 800 calorie per day ketogenic diet, worked many very difficult jobs, and did a number of other things that have required sustained discipline, as have others in the family. He doesn’t understand that the difference is that he enjoys self-imposed misery and the feelings of superiority he gets from it, which not only leads to a lack of balance in his life, sometimes strains his closest relationships.

> My Dad is like that and doesn’t understand why nobody else in the family gets off on self-imposed austerity.

My gut feeling: men of a certain generation seem to have confused the skill of seeming aloof-- like when meeting a stranger or thrust in a new situation-- for being emotionally unaffected in general. One sign I associate with this would be talking only in the past tense about having felt certain emotions, but you never really witness the person feeling or expressing those emotions (outside of anger/frustration). Alternatively, the person may never really engage in discussions about certain negative feelings, unless it's to offer low-effort problem-solving advice to others.

This is difficult because there are obviously times when a small, seemingly insignificant problem can trigger an outsized emotion. It's natural and helpful to be able to sit with that negative emotion-- to feel it, express it and talk about it as an emotion you are experiencing-- to be able to eventually come to terms and get to know better whatever it is that's driving it. It's scary to do, but most people have some techniques for doing it.

If you have few or no tools to do that, it must generate an immense amount of stress. Hence wacky alternative stress-relieving techniques that are more physical and less emotional in nature. (Plus the projection of "lack of discipline" makes me wonder if he'd feel shame from sitting with a negative emotion.)

I’ve seen that in people though I don’t think it really describes him, specifically. He just really enjoys a lot of things in life the way some people really love getting the most punishing workouts possible, and would probably do it even if there were no health benefits.

I don't find it difficult to talk about negative feelings, as long as no one is listening. Talking to other people is mostly useless these days, they're all busy hiding from themselves.

And if you try to point out, even gently, where "the real them" may be hiding, you get an almost violent denial response.

+1 insightful

A good technique to help w this is "affective labeling" (sorry, citation needed, I think I got it from one of Anne Laure Le Cunff's typically awesome newsletters/posts). Set a 5m timer, start writing words that describe your emotions and don't stop writing for even 2s till the 5m are up.

> +1 insightful

As an aside, I miss the slashdot ability to optionally assign a property to a vote. It would be neat to have some sort of indicator in addition to the greying out of downvoted or flagged comments to show specific types of upvotes. This has obviously proven to be the better system overall, but it has its pluses. Too bad it also had a bunch of swastikas and 4-Chan-esque trolls.

I'm not sure I agree this has proven to be the better system.

Slashdot had, for many years, fairly insightful commentary with that system. The fact that it has since become less insightful is, I think, less a reflection on the voting system in comments and more on people moving from the site wholesale for various other reasons.

I don’t mean the more effective voting system — I mean the more effective system overall. I don’t really think that’s controversial. As I said, I like the Slashdot voting system

This reads like a description of someone with an avoidant attachment style.

> One sign I associate with this would be talking only in the past tense about having felt certain emotions, but you never really witness the person feeling or expressing those emotions (outside of anger/frustration). Alternatively, the person may never really engage in discussions about certain negative feelings, unless it's to offer low-effort problem-solving advice to others.

That's really insightful! Thank you. Saving your words in a scratch note for later

That's a lot of psychoanalyzing of people you don't know.

If it helps give you some perspective, I've been through a decade of therapy and years of group therapy, and I haven't found that my interest in "discipline" lessened or became less relevant as I've come to grips with emotional issues and learned to relate to people in different ways. There hasn't been much interaction between the two, except that when I'm doing well at one I tend to do better at the other, for the obvious reasons.

An alternative explanation is that voluntary suffering is a comforting reminder that you can do it when you need to, as well as an effort to maintain that ability. My observation is that people who engage in "gratuitous" suffering are people who were raised by parents who didn't pass on the basic skills of discipline (among which are important emotional skills) and had to learn it from scratch later in life. Since they didn't grow up with it, they don't take it for granted, and they exhibit the "zeal of the convert." Or, if they never achieve it, the persistent lack keeps it at the front of their minds.

The parent poster seems to have quite a lot of discipline but doesn't feel any need to remind himself that he has it. Maybe that's because he learned it as a child from his father?

My father had a hard and restricted life growing up, and he wanted me to grow up in a more free and easy way. He wanted me to feel free to goof off and enjoy myself. I certainly learned that, but I also grew up with a lot of anxiety about my inconsistent ability to apply myself to things I cared about. Sometimes I did, and thrived, but very often I disappointed myself. I was especially poor at boring things and things where consistency mattered, such as taking care of my health, but often, even at the things I was good at, I failed to put in effort at a crucial time and screwed up something that was important to me. My easygoing father wasn't going to tell me I "lacked discipline," but my frequent underperformance and self-failure told me loud and clear.

So I spent years figuring it out and getting better at it. Like anything that doesn't come "naturally" (i.e., wasn't learned in childhood) it has always felt like an artificial bolted-on part of myself that could fall off at any moment. So I consciously tend to it. I don't show more discipline in my life than other people, but I certainly show more interest in it, and I do some things that probably seem weird to other people. Other people probably think it's a meaningless focus that has no impact on my life, since I'm not conspicuously different in my habits and accomplishments. But not being conspicuously different is the accomplishment!

A lot of people can relate to the effort required to maintain a healthy weight after growing up overweight. People who take a healthy weight for granted might think that an above-average amount of attention and effort should yield an above-average physique, or what's the point? They might feel amused or condescending towards their friend who thinks and talks so much about what they eat but looks very average. They might get annoyed that their friend declines an extra round of drinks or skips dessert. What's the point? It's not like they're maintaining a fabulous physique. They look like anyone else, even slightly below average. Clearly their obsession with eating doesn't accomplish anything other than annoying the people around them. But it does accomplish something. It lets them be closer to normal.

“Enjoys misery” is an oxymoron I think. He enjoys joy, which he gets from doing difficult things. I’m just taking your dad’s side on this because I suspect I share some of his tendencies :)

Ok, rather than enjoying self-imposed misery he enjoys the process of imposing and Meta state while experiencing self-imposed misery.

You know, I think you might be right. ;-)

Or challenges, overcoming seemingly impossible obstacles, I need that to feel alive.

But it's all for me, I have no cravings for telling other people. The exception would be if I see a possibility to inspire someone.

Austerity is not the same a misery. In some ways I live an austere life but I am happy. Misery comes from poverty not self imposed austerity; the first is often imposed by the outside world whereas your father's and my austerity are, as you say, self imposed and under our own control.

You’re making arbitrary definitions for those words. Austerity can absolutely lead to misery and some of the happiest times in my life have been some of the most impoverished.

> Austerity can absolutely lead to misery

I didn't say that it couldn't, merely that it doesn't necessarily do so.

Austerity often comes naturally with age, just because spending money requires effort and energy older people don't have.

Does he not understand the situation even when you lay it so bare in front of him? People tend to get off the course sometimes on their own, but smart mature ones prefer honest correcting feedbacks (to certain extent), if it means ie better more stable relationships with closest ones

He’s pretty hard-headed, but so are his middle-aged sons. These days we’re all grown-up enough to know when to sort of shake our heads and change the subject. My mom has her own way of setting boundaries which seems to work for her but unless she wants to talk about something specific, it’s normally nothing I need to even think about. She feels comfortable enough confiding in me though. To be clear he’s a 100% stand-up guy, doesn’t have an anger problem, and even though he can be frustrating to deal with sometimes, there is never a question about him doing what’s best for his family, even if that means swallowing something he’s annoyed by if it’s necessary.

> I’ve always thought that deliberate, controlled suffering gives you a mood boost.

That's not an alternate "theory".

https://www.smithsonianmag.com/smart-news/theres-scientific-...

> People who self-harm, writes Arnold, have “learned that, while the pain peaks with self-injury, it then comes down the other side. The physical pain lessens – as does the emotional pain.”

People don't self-harm because it hurts. They self-harm because it _feels good_. Pain is "pleasure", for lack of a better phrase.

I was a hobby beekeeper for a few years and grew to enjoy getting stung. It still hurts like hell at first but the ride down is lovely.

Spicy foods might be another example.

There's also the not so constructive tendency to punish the body for what the brain comes up with and the feelings that come with it. It's really the only part of yourself you can harm.

Most of them self harm because the removal the pain feels good - and it takes with it some emotional pain.

Though there probably are some masochists that truly enjoy the pain, but that's a different condition than the more common I-hate-myself-so-I-hurt-myself.

> removal the pain feels good

Not quite. The pain causes an endorphin release. It's also addictive (not technically by the DSM sense, but those who do will often call it as such) and has been compared to heroin.

This interview about dopamine and homeostasis in the body would support the idea that resetting that system through suffering would likely be a valid approach:

https://youtu.be/R6xbXOp7wDA?si=iUUfMZe05DO0wR5K

When I learned about the hedonic treadmill I thought back to a number of athletic programmers I’ve known who always seemed to be a lot more put together than the rest of us. I always figured the relationship went the other way. That having your shit together meant more time for activities. It may be the other way around.

Physical activity is a life saver for me, it allows me to release energy that would otherwise cause trouble down the line.

If you can handle running 5 miles, you can handle that terrible refactoring task you discovered this morning.

As a person who did 21km run in fasted state (didn't eat for 36 hours before) and then swam in a 7 degrees pond with ice, I can definitely say: NO.

I tried for 8 hours straight to code just a little bit, but was unable to. I guess that is burnout, or, in general, understanding that I am not interested in all this computer stuff anymore after doing it for 15 years.

Yeah, the other stuff sounds like more fun to me as well :)

I read somewhere, if you fast, the body thinks you can't find food, so it gives you more dopamine to motivate you to find more.

Interesting hypothesis. Mental acuity does seem higher while fasting. Is that a dopamine specific effect, or could there be a handful of hormones impacting mental state?

Anecdotally, I've observed I feel better with a certain amount of difficulty in my life and felt particularly bad when there was nothing -wrong- but I still felt depressed. If you don't have any problems you can attribute the bad feelings to, then you naturally start to consider the possibility that the problem is you and you're broken in a way that means you're going to feel bad regardless of how much your life circumstances improve. Which is a particularly despair-inducing thought to have.

Last year I cracked my hip joint and ended up in the hospital for a couple of weeks, doing physio to regain my ability to walk. I certainly don't want to repeat that experience but I was surprised that I felt less depressed during it, because there was clarity in what I immediately needed to do and I was focused on just getting through it, not existential angst.

I'm no stranger to discomfort. I enjoy it. Like, my bed is a piece of plywood with a blanket on it.

The increase in energy and clarity of my thinking, the tingly feeling in my body, and the improved sleep quality -- just to give you a few examples -- are hard to attribute to the mechanism you're talking about. To add to that, I regularly fast for five days at a time and I have not yet experienced the same kind of mental difference. This time I pushed it to two weeks because my energy levels continued to fluctuate upward until the 12th or 13th day.

You do feel a lot of relief that the boredom of fasting is over. But that effect lasts maybe a day or two or three. Certainly not months.

> Like, my bed is a piece of plywood with a blanket on it.

Other than the potential for mold accumulation (you definitely want some air to circulate), this is not actually a bad bed base for sleep quality. Depending on your size, it's likely better for you than some very expensive plush mattresses.

Plywood has give to it that a hardwood wouldn't, so what you're sleeping on isn't entirely rigid anyway.

But drill some holes in it :)

I fast somewhat frequently, and I don't really associate it with pain or discomfort, but I'm also doing it for 24-48 hours.

Extremely long fasts (like your two weeks) should come with a disclaimer, they're not for everyone.

If 14 days is extremely long, what is 382 days?

It's "medically supervised"

It’s also a major accomplishment which can boost your mood and confidence regardless of it’s direct emotional effect.

This... Reads a touch like baby manic depression.

Certainly, the highs feel better if you're coming from a low; but I tend to prefer my highs coming from mids. I will say that, although not a low, the sweet relief of getting through a stressful situation/project is great.

There's a flip side to that, which is anhedonia. If you're always at a mid, it's kind of harder to get the highs. But you avoid the lows, I suppose.

Anhedonia is sometimes used to refer to 'flat affect', which I guess could be taken as 'mid', but usually it is used to describe a lack of joy/desire that is quite common in major depressive episodes.

I believe this is a well-understood feature of the dopamine system? The sensitivity of the receptors is like a balance scale, and will correct to one side if the other is flooded.

Give yourself big dopamine rushes and the scale balances by reducing your sensitivity to dopamine and (crudely put) causes feelings of discontentment, and you’ll need more dopamine released to feel like normal. Alternatively, push down on the pain side of the scale by doing some controlled suffering — fasting, cold plunge, intense exercise — and the receptors become more sensitive, and you feel better.

I’m sure this is too simplistic of a model but it makes sense to me in terms of lived experience.

A two week fast is incredibly difficult, accomplishing it, taking part in etc is very meaningful. Consistently throughout time and history a sense of purpose has been remarked as key to human happiness.

https://en.wikipedia.org/wiki/Asceticism

> Or rather, the relief after the suffering has ended

Good luck if you are suffering from most forms of depression in getting that relief since everything is suffering.

The obligatory “To love is to suffer. To avoid suffering one must not love. But then one suffers from not loving. Therefore, to love is to suffer; not to love is to suffer; to suffer is to suffer. To be happy is to love. To be happy, then, is to suffer, but suffering makes one unhappy. Therefore, to be happy one must love or love to suffer or suffer from too much happiness.”

> It’s hard to say why it worked

Behaviour therapy would say that it worked because you took some action to improve your life and counter the depression. (Even cognitive therapy says that small, meaningful actions can have a dramatic impact on one's depression). The motivation and action of fasting, and the positive and noticeable / observable physical effects of fasting changed your focus from your depression, which alleviated your depressive symptoms. Once depression alleviates, you start thinking more clearly (make less cognitive distortions in your thinking) which further leads to a 'normal' mental state of well-being (in an otherwise mentally healthy individual).

Yes. A long fast can reduce overgrowth of harmful bacteria that survives on a continuous supply of food. This paper mentions Morganella morganii, which is an example of harmful bacteria that thrives in a environment full of undigested proteins and carbohydrates.

If your depression remained abated after resuming a healthy diet, I'd say the microbiome hypothesis is intriguing. Otherwise I'd there are way too many complicating factors at work during a fast to dwell on that.

Also, you could toy around with different fermented foods while making no other changes.

I completely cured my severe anxiety and minor depression by eliminating wheat and sugar from my diet. I come from a family where everyone has digestive issues and some type of illness that is tentatively linked to the microbiome.

For how long, is the question though? Depression and anxiety are like the "common cold" of mental health suffering, and everyone endures it a few times in their life.

Well, it's been about 10 years. And I'm still a completely different person with absolutely no signs of it.

The lifetime risk of clinical depression is someething like 30% for men and 40% for women in the west.

Recurrence is about 50% for people with one major depressive disorder occurence, and 80% for people with 2.

That makes it more akin to something like cancer in western countries with regards to lifetime prevalence (but not recurrence)

That may be true for severe cases. But if you consider the checklists used to determine depression, it offers the results on a scale. For example, the Becks depression Inventory (BDI - II) suggests that the depression maybe either "minimal, mild, moderate or severe". Similarly the Burns Depression Checklist (BDC) tests identifies depression as either "mild depression, moderate depression, severe depression or extreme depression". Anxiety is also measured in a similar scale.

The "mild or moderate" segment of depression, or anxiety, is what is said to be a more common short-term occurrence amongst all of us. Most of us manage to often deal with this kind of "situational" depression / anxiety due to some stressful event (losing a job, death, breakup etc.), on our own. But long-term and / or severe / extreme depression is what often requires an outside intervention.

Yeah, no. Please further educate yourself before saying this out loud again.

A lot of people who have no fucking idea what's it's like to have debilitating mental illness apparently.

This has me very curious! How did you decide on eliminating wheat and sugar? Or did you cycle through various eliminations until you found a combination that worked? And how did you know when to keep going/stop?

I was doing a big job for some hippies, and they fed me lunch every day. And even though I thought it was bullshit, I was polite and ate their gluten free, sugar free, organic, free range, etc, etc food. My entire life I hated eating, but I quickly realized that I really enjoyed eating with them, and I felt really good afterwards.

And since then I've done a lot of experimenting and reading other peoples thoughts, and reached the conclusion that simple carbohydrates are fucking terrible for you, for multiple reasons. The biggest is that it causes an insulin spike. If you're then physically active, you'll burn off the sugar you just ate, but your insulin levels stay high, so you'll never start burning your body fat. You just get hungry and eat more sugar.

> My entire life I hated eating

this makes it sound like you have some sort of celiac, gluten allergy, or low-key diabetes

I cured my sugar addiction with a 2 day fast. I found it remarkable tbh

There is also a known phenomenon of "starvation euphoria." I don't know at what point of caloric deficit that kicks in, but it probably varies dramatically.

I assume it was a water fast. Did you supplement with anything? Did you have a doctor's supervision during the 2 weeks? How did you reintroduce food? I've always been fascinated by long fasts, but I'm scared to try them.

I had some electrolytes at first but ditched them on the third day. After that it was just plain water. If I had to do it again, I would take potassium and table salt throughout.

I did have friends and my girlfriend with me for a lot of it.

I didn’t do anything special to break the fast.

Yup, potassium - or part of a banana. I've read that most deaths attributed to crash diets are caused by cardiac problems caused by potassium deficiency.

Not eating for a couple of weeks won't kill healthy people. You don't have to waste your doctor's time unless you're old or frail.

Asking for medical advice is a waste of your doctor's time? I'd rather do that than trust a bunch of random posts from people I don't know on a technology website.

They could be helping someone who actually needs it. Asking for time you don't need is unethical.

Good for you! This is how it all starts. By adding foods back slowly you may start to find what foods are a trigger for gut inflammation and depression.

There is one medical diet, called the FODMAP diet you might want to look into. It helps you find what foods might be causing some bacterial in your gut to become imbalanced.

I am not at all saying it is all you microbiome, foods may affect us in so many more way than only in the gut. It may be that not eating has lowered oxidative stress in your body allowing your mitochondria to recover and are now able to provide the energy you need.

I think there are other plausible answers, and I'm generally skeptical of people who believe there are diet cure-alls, especially for depression. I'm not a psychiatrist, but I do have a bipolar 2 diagnosis. I only found out it wasnt a unipolar depression because I had a hypomanic episode. I can only describe a hypomanic episode as a wave of constant energy, and I've also heard it described as: 'being on meth for a week straight'. It gave me the energy to forego food for multiple days because I didn't feel the pain of hunger pangs. I also didn't sleep for a few days, not because I wanted to, but because I just had too much energy.

I'm not a doctor, but hopefully this is an example of other places to look that aren't diet related.

been collecting for a while, happy hunting https://github.com/cutestuff/FoodDepressionConundrum

I certainly agree there's a connection from the gut to the rest of our body (including mood) that we still don't understand... But I'm curious if you've done anything to rule out psychosomatic ? I saw a brief mention that you think there is a link to childhood experiences, which means you do agree there might be a mental connection... Have you tried a blind experiment at all? I could see it being relatively possible if you had someone prepare something liquid, steps were taken to conceal the flavor, and perhaps using a straw to limit how much you can notice.

I did have some experience with dog food, where I'd feed the dog and after a few weeks noticed joint pain. I'd not paid attention, but there were beets in the dog food. That was kinda blind until I noticed symptoms. I realized, I was licking the leftovers on the spoon before I washed it by hand. Not sure this counts as blind testing.

Sadly it feels impossible to find a doctor in germany that knows what to do about it. The last success was with something like oxalobacter. For a few months now I could eat at least some salad, but seemingly that effect weakens over time.

So I think I have found a probiotic that works, but it doesn't stick well. This article mentions genetic traits being connected to the biome. So I think I'll have to have genetic testing eventually, but I'm way paranoid to hand over my genes to some random lab.

Interesting, I had a bout of depression that I believe started when I did a monthlong low carb low calorie diet (with doctors and nutritionist). Gut health is a huge factor.

Low carb and low calorie for a month sounds rough in general. Maybe the depression could be attributed to exhaustion and a suppressed metabolism as well.

Very individualized. I have drastically better gut health, skin health, energy when on a low carb diet for an extended duration.

Maintaining that diet for an extended duration, however, is always the challenge when others in the household do not follow it. Logically, I should stop being a baby and just power on with it. Or at least determine what in my "normal" western diet negatively impacts gut health/skin health and overall energy.

Having dealt with strange neurological states, i somehow got sensitive enough to perceive what could be changes in the gut microbiome (depending on diet, probiotics intake, antibiotics) these would have similar effect as change in serotonine based therapies, albeit short lived.

I'm listening to Brain Energy by Christopher Palmer and he talks about this.

I wonder if people who are questioning if fasting 2 weeks is the main cause of interrupting your depression did ever fasted a week. Would you consider that you "cured" the depression?

Yea. Many of the comments hurt me to read. I'm trying to remind myself that they come from a place of curiosity and wanting to rule out confounding variables. But they do make a lot of assumptions about me and things I know and/or do.

To answer your question: I hesitate to use the word "cure", because 3-4 months on, I'm starting to wonder if certain things have begun to slide back, or if it's just been a challenging week. Time will tell.

A datapoint that I did not mention in my first post was that there was a negative, persistent, digestive side-effect that paralleled the positive mental changes. As that has faded, so have some of the noticeable mental changes. I'm still doing better, but maybe with less energy than a month or so after the fast. I hope not, but maybe this is something I'll have to repeat every now and then.

Negative persistent digestive state could be related to the new digestive context you created after a 2 week fast, which is a huge event in a life. How much, how often, what and when you eat should be adapted, following your feedback rather than theories. Alimentation is specific to each. Good luck dude, you can fully heal!

Just a thought from a random stranger but you might want to consider the possibility of celiac disease. It takes a couple months for antibodies to build up so the time scale you mentioned here stood out to me. Celiac disease has huge impacts on mental clarity and energy.

Have you done any experimentation with pre/pro-biotics? Just wondering if your fasting adjusted your gut biome, but now as you've resumed whatever diet that biome is being modified based on the fuels available to it.

Yeah might be worth regularly eating foods like kimchee or kefir. Or high quality yogurt. It seems to help with my psoriasis which is related to inflammation.

I'm pretty sure vegetable sources are way more potent than yoghurt, fermenting your own veggies is not that complicated. Nor is making your own yoghurt. The thing is, it's alive, so shelf time matters a lot.

I wonder if shorter fasts between the long ones would make a difference?

Ignore the hurtful comments. A good portion of people don't have much empathy for others, combined with the anonymous nature of this forum, makes people say hurtful things.

Good luck on your journey.

Thanks, I appreciate that. And by the way, I had the same thought as you. I’ve been doing monthly 5-day fasts just to see what would happen. So far not much to report, but I’ll wait until 6 months have passed to draw conclusions.

At the most extreme end of the other side, Buddhist monks, in addition to not eating meat (or, often, aliums like onions and garlic), also don't generally believe in dinner—they have to eat all their solid food for the day before noon, so you could view this as fasting for half the day every day.

(There are some caveats... At least for the Tibetan monks I knew, morning prayer is early at like 5am and comes with a sort of pita bread and tea, bedtime is closer to 9pm, and during these 9 hours there will be more tea. With a little googling I am able to confirm that some of the "pita" (pao balep) is consumed at the lunch tea, and I think this is after the lunch meal, so it might be 1pm. I think there's none at the evening tea that you'd have around sundown? Also in terms of calories the Tibetan tea is “bulletproof,” consisting of a very long steep for the leaves to extract maximum bitter flavors, that get mixed with a bunch of yak butter and salt. So liquid calories are very much a thing for them.)

I commented above, Checkout Brain Energy by Christopher Palmer

Very interesting! Did you take in any vitamins/minerals? Did you drink coffee/tea (no milk/sugar of course)?

Interrupted or fixed? And lemme get that regiment?

Did you already exercise regularly?

Would also want to know this, since one probably needs a lot of muscle to go through this 14 day períod, but those muscles would come from exercising, which also help reducing depression.

IIRC the body breaks down stored fat well before it breaks down muscle.

Yea, I'm in good shape. I commute by bike and was spending most of my free time at the gym.

What was your fasting regime like? Did you have water only fasting for 14days straight? Meat only?

strange, I guess bacteria wasn't happy at all during you fasting

fasting changes the population of the microbiome in your gi tract...

Diethanolamine:

General description. Diethanolamine (DEA) is an amino alcohol commonly used in the preparation of soaps and surfactants, agricultural chemicals and in textile processing. It is used as an absorbent for capturing CO2. Its toxic and carcinogenic effect has been studied.

Diethanolamine is widely used in the preparation of diethanolamides and diethanolamine salts of long-chain fatty acids that are formulated into soaps and surfactants used in liquid laundry and dishwashing detergents, cosmetics, shampoos and hair conditioners.

I think it's important to clarify that DEA is used in _industrialized_ processes for soap and detergents. As a person who makes their own at home, I can tell you that no home recipe I've ever seen has introduced DEA into the process unless I'm missing something. I can't speak for shampoo, since I've never tried to make it (I purchase shampoo bars from another home soap-maker).

Please feel free to correct me, since I'd love to be sure.

I worry about this a lot. I also make my own bread for the same reasons; I find that industrialization of consumables is introducing a ton of contaminants into our bodies, the effects of which we are not fully cognizant of. Where possible, I avoid participating in that game because of how I view the trade-off; it does not make sense to me to save time by buying the products instead of making them at the risk of shortening my lifespan.

Again, I'm open to different thinking on this. In recent years, I have just felt a powerful draw to get back to basics and understand what I am consuming in a responsible way.

Do you know if the regulations regarding contaminants in both soaps, as well as consumables, is more stringent in the EU (beyond the "Fanta-to-Fanta" comparison)? In other words, would you feel more comfortable eat something basic like bread and other consumables from supermarkets in the European Union vs the US, or not? Can you eventually share a few thoughts on this?

I am not well versed in EU regulations regarding foods, aside from a recent experience in Iceland which boils down to the Fanta example. That and the fast food chains that we view as ubiquitous in the US were either sparse or did not exist in Iceland. We did not go in the one we saw, so I do not know if the menu was different or not, like one might experience in Japan.

Any thoughts I could share are my own concerns and opinions based on my experience and observations of the food and health industries in the US. It might be best if someone more expert on comparing the regulations between the two regions chimed in.

I mentioned the bread example because that's what started it for me during the Covid Pandemic isolation. I got bored and decided to learn to make bread, but did not have much to work with, so I found really simple recipes. Bread, as it turns out, only needs water, flour, salt and yeast to come out tasting absolutely delicious to the point where a loaf does not last long enough in my house to go stale. When I compared that to industrialized bread (both off the shelf and from the ersatz "bakeries" found in some of our large grocery chains), I was curious then horrified to see the amount of ingredients in those products that offered no discernible nutritional value and existed only to make the product more shelf-stable or more addictively appetizing. I say this as a person who grew up eating Wonder Bread, which I absolutely no longer consider to be "bread," but more of a sponge-cake.

From there, my wife and I started really looking at the products we were consuming and realized that we did not really know what was in 90% of them. We were just trusting the manufacturers and regulations to keep us safe, because that's what we're supposed to do as good consumers, right? It was alarming, to say the least, and even more alarming is the fact that this is not a new fight in the US, dating all the way back the late 19th/early 20th century. When the driving force behind regulation is profit margins, the rules for evaluating risk to the population start to move around in uncomfortable ways, but because of marketing and branding, we're taught at pretty early ages to trust these companies, sometimes even wearing their symbols as a badge of identity.

I'm never going to be one to say "Food company X is trying to kill us!" because that does not make good business sense. I've said it before on HN, but I'm not convinced that a lot of this regulatory slack and the declining qualities of our food is meant to intentionally harm us, but more born from the short-sighted thinking that allows executives to say something like "well, nobody has died from chemical X in product 1, yet, and chemical X can displace some of the more expensive chemical Z, so, maybe we can increase the amount a bit to bolster our profit margins?" Then they do it, quietly, and nobody dies, so they do it again...and a again. Longitudinal studies are cast aside in favor of only focusing on immediate results.

And so, we have things like canned pulverized Parmesan cheese that contains sawdust as a filler, which might arguably be harmless, but being robbed of product for the same price as the old version should also spark our inner consumer to go "hey, wait a minute..." even if we ignore the possible long term heath effects on the population as a whole. Our term for this now is shrink-flation, but it's definitely a very old tactic. This became another driving force behind my wife and my decision to try and set aside time each week to make certain products. We know what we are getting for our money, we know what to expect, and we know what is going into each one. Do we still buy other soaps or get the occasional shelf-stable pie? Yes, of course. But is our consumption of these items has plummeted to a last resort of convenience or just a rare treat.

Sorry, this turned into a blog post and I'm still skipping a lot of the nuances in my thoughts on this matter so pardon any disjointed structure in my narrative.

In the end, the lesson I learned can be summed up as _pay attention_. Read the labels, do the homework, and decide as best you can with the information you have at the time. We vote with our dollars, so spend them wisely.

I thank you for the blog-post length reply and I am sorry I triggered that with my simple question in disguise. I knew it was hard to answer.

It is funny that you specifically mentioned the bread. I go a fair bit between Austria, Spain, Greece, the UK and all around Asia.

We have a lot of really dark and heavy bread in Austria. Austrian bread frequently incorporates a variety of whole grains, including rye, spelt and whole wheat. Darker, denser loaves like Roggenbrot (rye bread) and Dinkelbrot (spelt bread) are the norm here. Austrian bread is typically made with just flour, water, salt, and natural leavening (sourdough or yeast).

I didn't ask you the question to gleam with that, am I'm apologizing in advance if its coming through like this. My point is the additives. And it might get back to that Fanta-to-Fanta comparison, but with so many other products, many American store-bought breads contain added sugar or high-fructose corn syrup, whereas Austrian breads rarely do.

I also think that a lot of additives or chemicals are simply banned in the EU leading to a lower shelf life of products, but generally more natural products. Like Potassium Bromate, ADA, BHA & BHT etc which are banned in the EU. Together with the corn syrup found seldom in eupean products, or Austrian.

Spain and Greece have less of the black and dark breads, but that movement is slowly coming. Spain has a lot of really really really great food, and very high quality.

Asia is a different story. There are some artisanal bakeries popping up in places like Hongkong, Singapore, Thailands larger cities, Malaysia etc. But in general, stores have these softy loafs of what we call toast bread. But then, they don't eat a lot of bread :)

Not sure where I'm going with this, if at all anywhere, next time you come to europe, try some of our bread.

My friend, I have considered going to Europe specifically for the bread! And bakeries in general, of course :)

Stay healthy!

Iceland is also interesting because they don't have over the counter drugs (iirc not even acetaminophen). But anyone can walk into a clinic, tell them what's wrong and if they think it appropriate they'll give you whatever drug they think you need.

Got a bread recipe you particularly enjoy that you'd like to share?

If you haven’t baked bread before and want a great starting recipe, try Jim Laney’s no-knead bread.

Some tips:

1. You can halve the amount of salt. (1 bakers’ percent of salt is plenty. I don’t know why most recipes call for 2%.)

2. Active dry yeast is obsolete, but that doesn’t stop it from being prominently sold in grocery stores. Get instant yeast instead. SAF Red or SAF Gold are excellent choices. Instant yeast will work in a recipe written for active dry yeast, but active dry yeast may not work in a recipe written for instant yeast.

3. Get a scale and use it.

4. You don’t actually need King Arthur Bread Flour, but you should use a high quality bread flour. I experimented once (quite a while ago), and IIRC Gold Medal worked well and Pillsbury was okay. King Arthur does make a consistent product, which is nice.

Pretty much any of Ken Forkish's recipes. Linked below is one that I find really accessible and a great intro for folks new to bread baking who want to get a bit more into the finesse side of the experience. The way the dough is handled is important, I've found, since it's very easy to overwork it. Ken does a good job of describing the process.

If you were to buy only one bread book, I would highly recommend _Flour, Water, Salt, Yeast_.

[1]https://www.epicurious.com/recipes/food/views/saturday-white...

That’s a good book and has lots of good recipes, but…

IMO autolyze is at best a minor improvement compared to just not doing it (maybe called “fermentolyze” in this context). (In my experience at least some degree of pre-kneading/aggressive mixing rest makes a big difference, but this recipe and Laney’s no-knead don’t do that.) But autolyze is quite the complication, especially for new bakers making simple bread! With the autolyze step, you have the complication of trying to mix yeast and salt into dough, which is not so easy. Without the autolyze step, you just mix the dry ingredients, stir, and add water.

So I wouldn’t recommend this recipe as a first serious bread for a new baker.

My favorite is Russian Borodinsky bread with caraway seed. You can find a standard GOST recipe for it online, but be warned that it's a 48 hour process that includes scalding the dough.

Yes, you are incorrect. DEA is in many products, and here is a website that show which products do not contain them. Diethanolamine used in some dishwashing soaps as a foaming agent and emulsifier.

https://www.skinsafeproducts.com/search/products?brand_ids=&...

This does not look correct. For example [1]:

  DEA (diethanolamine) and DEA compounds are used to
  make cosmetics creamy or sudsy. DEA also acts as a
  pH adjuster, counteracting the acidity of other
  ingredients. DEA is mainly found in moisturizers
  and sunscreens, while cocamide and lauramide DEA
  are found in soaps, cleansers, and shampoos.

[1] https://davidsuzuki.org/living-green/the-dirty-dozen-dea-rel...

Apologies, I'm not clear on what you're pointing out in my comment as incorrect. I specified that DEAs are used in products that come from industrialized processes, that you won't find them in home-made products of the same nature.

I'm using "industrialized" to mean "mass-produced" here, as in stuff that comes from a factory rather than a small work station in a DIYer home. I wonder if this may be causing confusion?

The article you linked is likely speaking of mass-produced products, but does not go so far as to specify that (they should). I separate the two since they really are quite different. If you put one of my bars of soap up against Dove, for example, you'll notice that mine do not lather nearly as much a Dove, nor do they have that "buttery" texture of commercial soaps. DIY soaps typically only need lye, distilled water, and olive oil then whatever you want to add for scent. DEA does not enter the equation in a home-made version.

I’ve taken to rinsing my glasses and bowls before using them for liquids. I figure the transfer from a plate to a sandwich can’t be bad enough for me to go full OCD on this (and wet sandwiches are weird), but if it’s coffee or soup I’m definitely getting a dose of any residues the dishwasher leaves. The higher efficiency ones have been clocked leaving more detergent residue behind.

from https://www.fda.gov/cosmetics/cosmetic-ingredients/diethanol...:

The following are some of the most commonly used ingredients that may contain DEA:

    Cocamide DEA
    Cocamide MEA
    DEA-Cetyl Phosphate
    DEA Oleth-3 Phosphate
    Lauramide DEA
    Linoleamide MEA
    Myristamide DEA
    Oleamide DEA
    Stearamide MEA
    TEA-Lauryl Sulfate
    Triethanolamine

I can't believe Lauryl Sulfate is in nearly every toothpaste. I don't know if I'm some rare case freak, but that stuff butchers my mouth.

It takes less than three days of accidentally using toothpaste with that stuff to cause me two weeks of miserable mouth hell from all the ulcers that form.

I'm not sure how rare it is, but as an anecdote when I was a teen I knew a kid who had a speech impediment and slurred their words really bad/was kind of mush mouthed.

We were on a group trip for about a week and had forgot their toothpaste and had borrowed someone's 'natural toothpaste' stuff. By the end of the week they were far more intelligible in speaking and were stating it felt like they mouth deflated. They had an undiagnosed allergy to toothpaste their entire life and no one had recognized it.

> I don't know if I'm some rare case freak, but that stuff butchers my mouth.

Yes, and also get a generalized allergenic test since you are obviously alergic to something and it might be a lot bigger group than you think.

The connection between canker sores and SLS is pretty well known and not rare or caused by some other allergy.

I don’t know where my parents picked up this trick, because everyone looks at me like I’m crazy when I mention it:

Relatively dry mouth. Milk of magnesia. Q-tips. Paint the sore spots with MoM. It thickens and forms a film, which cuts down on the tenderness.

I would try one spot if I were you. As bad as you described it, if that helps more than it hurts you might try gargling the stuff.

I came here wondering if I am the only one not knowing what Diethalothingythings are. Thanks.

I've checked a few shampoos i have at home and fortunately none of them had it (they had SLES which has its own problems but seems benign in comparison).

I don't think you'd see it on the ingredients list. It would be used in the factory for some of the raw ingredients, and wouldn't be on the ingredients list because the intention is that none ends up in the final product.

Just like you don't see "grass" on the ingredients list of yogurt...

It is on the ingredient list when present. I’ve seen it on many body soaps and shampoos. It could be listed as DEA, or as one of the many other items listed in an earlier comment in this chain

Ouch that seems very bad.

That's how ingredients work, since they should not be in there they are not on the ingredient list ... and there should be random testing to make sure there is no contamination (if you live in a country which has actual laws regarding pollutants and contaminants).

Keto is the only thing that fixes my depression-like state. I discovered it doing short-term fasts and then learned about Keto. I tested it multiple times. Once I get off Keto I feel much worse within 2 weeks and after around 1 month I am at the total bottom again. Then go back to Keto, 2-3 days of suffering Keto Flu and I'm happy to live again.

You probably have gut dysbiosis causing inflamation of your gut and inflamation leads to depression like symptoms. This doesn’t mean you have to eat keto all the time, but rather that you should take probiotics to restore your gut flora. This way, you can continue eating a balanced diet without allowing that specific bacteria to become overpopulated. The best for me was using Lactobacyllus subtilis HU-58 alongside low-fodmap diet. The low fodmap diet is a shorter period of 1 month, then it needs to continue with the RENEW diet for 3-6months to 1 year. This whole period needs to be supplimented with hu58.

I had some gut bacteria issues and I think I was helped recently by using oregano oil and/or allicine (extract from garlic). Used both for a week, before had 2x antibiotics for suspected SIBO. I also used VivoMaxx 450 probiotics and sodium butyrate for 3 days so maybe it was it. All of these combined are cheaper than single curation with antibiotics so worth giving a shot in case of issues.

Thank you I'll check that out. Tho, for me, it most likely began as a post-flu complication, so I don't have much hopes.

Thanks. Very interesting.

Do you know why HU 58 is so special?

You should try epilepsy keto, that is 80-90% of calories from fat, to get the max benefits.

Checkout the book Brain Energy by Christopher Palmer

So is there a straightforward solution to keeping this out of our system and we just...don't?

"Where is this diethanolamine coming from? Well, it's not known to be a natural part of either human or bacterial biochemistry. Instead, it is an industrial contaminant, sadly, whose ability to be incorporated (at low levels) into animal and human lipids through the apparently-not-so-picky enzyme cardiolipin synthase has been confirmed for decades now."

Welcome to my hell of understanding. All these molecules were "deemed as safe" not because me knew everything about them but because we did not care.

This surfactant, diethanolamine, may also prevent the healthy function of lipids in the mitochondrial membrane, namely Omega 3. When you mess with the mitochondrial membrane you start to have issues with oxidative stress and a whole range of metabolic disorders.

For example: Cardiolipin synthase deficiency is a condition that results in abnormal mitochondrial function and morphology. It can be caused by mutations in the cardiolipin synthase (CLS) gene. Symptoms impaired viability, decreased mitochondrial membrane potential, and defective oxidative phosphorylation.

What you can do: Drink reverse osmosis or deionized water and eat as whole and fresh food as you can. Wash your dishes by hand and rinse them very very well using the most natural detergent you have.

Here is a way to find some DEA free products:

https://www.skinsafeproducts.com/search/products?products_by...

To nitpick slightly, DEA is not a lipid, it's an organic amine. It can be inadvertently incorporated into a lipid instead of a glycerol, creating a ... weird lipid.

Isn’t there also something about cancer cells being more likely due to metabolic defects in the cells?

Yeah, any change in oxidative balance could promote cancer.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7392807/

Well, most shampoos have a warning label about external use only so there is at least some effort to keep it out of a person's system.

It's absorbed through the skin, so that doesn't actually solve the issue of having it in your body.

the people down voting the idea of skin absorption as a meaningful vector for getting things into your body remind me of the people a hundred years ago who thought animals cannot feel anything.

I'm wondering if the plastics in modern clothing are similarly exposing our systems to microplastics -- maybe not as bad as cooking in plastic, but a constant light abrasion all day, every day, for your whole life.

Our biologies didn't evolve with these synthetics. Not a big stretch to think our biologies won't handle them well.

>I'm wondering if the plastics in modern clothing are similarly exposing our systems to microplastics

I bet we inhale a lot of it via lint.

I'd say more nano-plastics. And pathway is more oral ingestion or breathing them in when they get loose from clothing. For sure, form time to time we breathe in one of those super thin 'hair'.

Home dust is visibly composed out of those too and it takes just a bit of sunlight to see them dance mid air in non-small numbers. It would be impossible to not breathe them in, or swallow some on food.

https://ceh.org/latest/news-coverage/do-your-workout-clothes...

Looks like plastics can enter the body through sweat glands. I threw away all my polyester workout clothing (which I loved to use) because of this concern.

Call me paranoid but I'm going 100% cotton and linen. Not keen on getting my hormones disrupted by inhaling and absorbing microplastics!

> If and how our workout clothes are leaching microplastics and endocrine disruptors directly into our bodies is theoretical, though

From the linked article.

Also, I'd love to hear this from an article that isn't published by goop

Polypropylene seems to be a fairly biologically safe plastic. It makes a great base layer. And we serve hot foods in it.

Differently from simple chemical substances, microplastics absorption through the skin is kind of an extraordinary claim.

Until we get any evidence of it, I'd say the answer is no, it doesn't.

The dose makes the poison. And the phrase "absorbed through the skin" admits a very wide range of absorption rates.

Interestingly there are some materials the absorb through the skin far faster than you'd expect. ie. they soak in just like a tissue soaks up water.

hydrofluoric acid. Get some on your skin, and you don't even feel a burn. But within minutes or hours, you may have demineralized your bones, causing them to go beyond brittle

Dimethylmercury, for example. https://en.wikipedia.org/wiki/Dimethylmercury

True...but Hg(CH3)2 is so much of a "MSDS from the 11th circle of hell" corner case that only expendables in heavily armored moon suits should ever go near the stuff.

Yet a German synthesized it in his basement and used it to poison a colleague: https://www.theguardian.com/world/2019/mar/07/german-who-poi...

A crime as heinous as the substance that was used. It's a miracle that he didn't kill himself or one of his family members with it.

The paper seems to conclude that we do not know the safe dose. And we are not talking death, but suffering.

So taken together, there would seem to be good reason to continue to continue to unravel the long-hypothesized inflammation/depression connection, and particularly in regards to possible exacerbating factors such as higher levels of M. morganii infection or even higher environmental exposure to diethanolamine. We seem to have a lot to learn here!

This is a "you don't know what you don't know" thing. This article lays out a path way for a link between a chemical that is common in our lives and depression. That pathway is a common gut bacteria. The article ends with this:

"So taken together, there would seem to be good reason to continue to unravel the long-hypothesized inflammation/depression connection, and particularly in regards to possible exacerbating factors such as higher levels of M. morganii infection or even higher environmental exposure to diethanolamine. We seem to have a lot to learn here!"

diethanolamine is commonly used in liquid laundry and dish washing detergents, cosmetics, shampoos and hair conditioners. So you really don't know if your hair conditioner, shampoo or dish washing detergent is causing you inflammation & depression. Hmmm.

We, as in the institutions that supposedly protect consumers, work on the assumption that anything can be used and added until it is proven not safe. For example, thalidomide. We did not know it would cause deformed babies, so it was assumed to be safe.

Okay, so will some corporation knowingly use something that is hazardous, just to make more money. Well we have the Sackler Family and Purdue Pharma. Or you can go watch "Erin Brokovitch". And you might want to watch Matix again just for fun.

I mean this is why Nassim Taleb got extremely controversial with his via negativa approach during his Antifragile and Skin in the Game period (I am a huge fan of his writing).

>Drink no liquid that isn’t at least a thousand years old (wine, water, coffee). Eat nothing invented or re-engineered by humans.

The argument is straightforward, that human beings are a wildly complex multi-variate system and that throwing wrenches into a complex multi-variate system is generally a horrible idea (this heuristic is inverted and encouraged when the that system is breaking down).

Is there a bit of a naturalistic fallacy here? I think sort of, but not significant one. The idea that we could screw up our bodies is obviously there. The flip side of this coin is that I see something as trivial as depression and/or most other non-fatal ailments as completely independent of the evolutionary process, such that experimenting on ourselves to improve our life (again, quality of life over time should not be directly related to probability of genetic reproduction success, as is made obvious from the gay uncle hypothesis).

The implications of this extend to where you live, so a bunch of genetically German hippies living in California, pretending to be one with nature, really are being dishonest about the health benefits they pretend to have, when the argument pretty much insists that the region of evolutionary development occurs will be crucial to the benefits of that evolution. Taleb himself lives in NYC, not his genetic homeland of Lebanon.

We really just need to be more honest about how little we know about health... especially health outside of the highly reproductive window (13-45).

I agree with your major points, but depression is far from trivial. People sometimes refer to feeling a bit down as depression, but in medical terminology depression is specifically a disorder which has severe impact on your life, as well as being one of the main causes of suicide. As such it will be a factor in evolution, both as a cause of death and a cause of failure to reproduce.

The inverse of via negativa is that when the for potential death is there, interventions should be used without hesitation.

Insofar as death removing someone from the gene pool, again this is exactly the reason I bring up the gay uncle hypothesis. The idea being that the reproduction problems of gene for an individual may be outweighed by the reproductive benefits of the genetic family.

The other idea is that it may be caused by a common error like genetic disease.

So if, for the sake of argument, the findings here are correct and causal and should be acted upon, what exactly is one supposed to do about it? We've got the technology to detect gut bacteria but we don't seem to have good targeted ways to affect it.

> We've got the technology to detect gut bacteria but we don't seem to have good targeted ways to affect it.

Healthy diet, fasting, probiotics, reducing stress, among other methods.

An interesting way to affect gut bacteria is to get a fecal transplant. It doesn't look fun, and I don't know how well it works, but I bet that's the direction to go.

https://www.hopkinsmedicine.org/health/treatment-tests-and-t...

No wonder dogs like to eat shit off the ground

Cut things that contain diethanolamine from your home/diet/life?

Related to this, it's been shown that Long Covid sufferers have low levels of circulating serotonin due to viral inflammation downregulating the gut intake of tryptophan (serotonin's precursor) and is also (I believe) correlated with IL-6 similar to the article. [1]

Tryptophan is the only way your body can produce serotonin, and if you're not getting serotonin that is a problem and can cause depression, fatigue, irritability, brain fog, brain zaps, etc.

The cool thing is there's a workaround: The same paper also found that if you supplement with Hydrolyzed protein (basically pre-digested protein, you can get it off Amazon) the tryptophan variant therein uses a different cellular uptake pathway which is not downregulated. This type of tryptophan is not generally found in food, so it's not like you could just eat a bunch of turkey instead.

I tried it and I'll be damned, it worked. This is not medical advice btw, just sharing what worked for me. You have to take it very very slowly because your brain, having been serotonin-starved for years, will have a very, VERY low tolerance, so even though your body rate-limits serotonin production, even the "normal" amount is a big disruption and you can still induce Serotonin Syndrome if you're not careful. I take no more than about a 1/4 serving every other day.

Also, goes without saying but DO NOT combine with SSRIs / MAOIs, or anything else that modulates serotonin.

[1] https://www.cell.com/cell/fulltext/S0092-8674(23)01034-6

It's never a good idea to make definitive statements like this from a single unreplicated study, especially when it has serious methodological problems.

https://www.tandfonline.com/doi/full/10.2147/JIR.S456000

I realize you're probably just trying to help, but:

A) I tested this on myself with results which are consistent with theirs and which would be unexpected if their conclusions were off-base, which is why I'm comfortable making these statements.

B) There is no treatment for Long Covid and people have been suffering for years without any recourse. If my comment helps one person searching the Internet then I don't think it's a bad idea.

(Edited to be less snarky)

Well, as a pathogen (god knows what is going on in our guts, or our skin, come to that) it is rare, as article says. I worked in an NHS microbiology lab in the 70s and never came across one - probably wouldn't have known how to do so. One of our consultants might (he was obsessed with anaerobes) might have, but there are so many that might (or not) be associated with wounds that they are very hard to identify.

They are talking about in in the gut, not on wounds. Morganella morganii has a commensal(maybe) relationship within the intestinal tracts of humans.

It may be more pathogenic than we thought if it causes increases in IL6.

almost all bacteria and viruses (and most other things) have a commensal relationship with us, otherwise we would would have all be gone into grey goo. i wouldn't wory about our gut fauna.

They're commensal until they're not. About half the world's population have H. pylori living in their stomach, and most people are fine, but in many people it causes gastric ulcers.

This is probably a wild (~stupid) idea but can we develop drugs to elite particular bacteria, e.g. just kill Morganella morganii, akin to Ehrlich's magic bullet? Current approaches, I think, use antibiotics that kill a wide range of bacteria, the good with the bad.

How would such a thing work? Could there be enzymes specific to one species (or, at least, a family)?

I don't know about enzymes, but bacteriophages (viruses that target bacteria) are species specific, and have been used successfully as antibacterial treatments: https://en.wikipedia.org/wiki/Phage_therapy

Are there studies linking common antibiotics to depression?

Find a vegan / natural soap store in your city. Off the Botel in Denver is great,

https://offthebottlerefills.com/

Ive switched entirely to Bathing Culture myself, an all natural soap brand.

https://bathingculture.com/

Alternatively, biodegradable soaps deemed safe for camping may be another good choice.

See also Dr Bronner’s, Method, Pré de Provence bar soap.

This explains why my moods gets better for couple of weeks, hwne i take some antibiotics.

Causation != correlation. Not all bad moods are caused by bacteria and you’re not factoring in the fact you were sick and got well as a potential mood boosting factor

I'm inclined to believe that GP is rational enough to be able to notice if there were symptoms other than low mood that were so severe and troublesome that GP reacted with chronically-low mood.

And I'm inclined to believe that GP is competent enough at writing comments that if there were such non-mood symptoms, GP would've mentioned them.

(I don't know anything personally about GP: I'm going on the average rationality level of the writers of HN comments that report on the writer's own health.)

That's interesting. I always get a bout of depression when the weather changes drastically (increase in temp, drop in pressure). I noticed that when I'm able to poop again, afterwards it starts to get better. Maybe I need to take stuff to speed up digestion?

> it was one of the strongest causal signals in the team's GWAS analysis (2,801 microbial taxa and 7,967,866 human genetic variants from 5,959 individuals), and it was the only one that validated (M. morganii levels versus major depression) when they went back and checked multi-year health records taken after the original microbiota samples.

I don't know what any of this means, but it sounds very much like https://xkcd.com/882/

So, it is like that, but it's also not. A couple decades ago, with the advent of GWASes, because of all the multiple testing that was going on, there was an agreed new p-value threshold p < 5e-8. This was to account for multiple testing going on (how that number came to be requires more explanation of LD + other things).

That is the minimum threshold. This study found that peak was at p < 1e-37 or so. But that is where the biological analysis begins. Unlike social scientists, we don't stop with the statistical correlation, we then go on to look at what we know about that gene, the type of mutation, if it's a loss or gain of function, what role that gene has in various tissues, etc. And mendelian randomization is another way to unpick the causal direction of effect.

Not to say this is the truth or causal, but it's a lot closer to causal than what you are implying.

In other words, there is a likelihood of 1/10,000,000,000,000,000,000,000,000,000,000,000,000 that the statistical result was due to random chance.

In more casual sciences p < 0.05 is considered the limit of significance, i.e. less than 1/20 likelihood of statistical testing favoring the tested hypothesis over the null hypothesis due to random chance

If you are testing a single hypothesis, sure. But nowadays, statistics training really weighs on bonferroni correction, or other methods to deal with the issue raised by the above-referenced XKCD, whentesting multiple hypotheses.

> This study found that peak was at p < 1e-37 or so.

If true, this would be cause for someone to read through the study to check there are no maths errors, and if it holds up then to take action immediately.

This isn't a "wait for more science to come in and confirm" type thing.

> This study found that peak was at p < 1e-37

This is many orders of magnitudes better confidence than any physics experiment, it feels unlikely a biological result can even be this strong, so it makes it sound like a statistical error.

Bioinformatician here. These kinds of p-values are common in these kinds of experiments (GWAS, or association studies), and happens almost automatically once you get enough statistical power. The big problem is that once you have so much statistical power, you get very small p-values from small effects, and then the often-overlooked assumptions behind frequentist statistics begins to matter. Are your samples _really_ idenpendent and identically distributed values? No. Are they really normal distributed? No.

Also, things like gut microbiome and depression are linked through what some people call the _crud factor_, which are weak correlations between nearly all social aspects. For example, probably depressed people eat differently from non-depressed people, causing changes in their gut microbiome. Probably, there are variations in human population's depression rates and obesity rates (correlated with gut microbiome) that somewhat correlate. When you have enough statistical power, you see the crud factor everywhere.

I really appreciate your explanation regarding the crud factor. It adds a lot of intuition.

Out of curiosity, what is your perspective on gnotobiotic systems? I distinctly recall an example of a gnotobiotic mouse that, upon being provided a microbial sample from an obese mouse, started to have substantial increases in body fat despite a simultaneous reduction in feed. Would that type of experimental approach still run into the statistical difficulties you mentioned?

Well no. It's not uncommon for p-values to be even lower than that. We are talking about a specific SNP (allele) having a specific mutation being predictive of a phenotype / outcome.

So, a specific SNP mutation being predictive of a gene expression / protein is basically a p-value of 0.

Can't speak for physics experiments, but this is almost certainly not a statistical error

They are aware of this which is why they add that those strange lipids have independently been associated with depression.

I put a tally mark under "more bacteria than human"

It used to be called the gut feeling column, but once the Alzheimer's links were confirmed more strongly i felt it needed to be addressed with more gravitas.

I will read the papers tomorrow but this should be easy to test, I think? Immediately cease use of any product that contains dea or analogs.

And since it's lipidinous, maintain weight? Ia this heretical?

to access the report, click "accepted version" in the left-hand margin https://www.repository.cam.ac.uk/items/9a051aa7-0fa4-46a5-88...

I ran the study through NotebookLLM and asked for some applied insights.

Prompt 1: based on the contents of the paper and logical deduction, what steps can someone take to apply the lessons learned from this study?

Response 1: [a little too scientific...]

Prompt 2: explain this in more common terms and concepts

Response 2:

Okay, here's an explanation of the study's findings in simpler terms:

This research paper explores how our genes and diet affect the community of microbes living in our gut, and how these interactions can impact our health. It's like looking at the complex ecosystem inside us and trying to understand how different factors influence its balance. The study used a large group of people and analyzed their genes, gut microbes, diets, and health records to find these connections.

Here's a breakdown of what it means and how you can think about applying it to your own life:

* *Your genes play a role in your gut:* Just like you inherit traits like eye color from your parents, you also inherit tendencies that affect the types of microbes that thrive in your gut. The study found many specific genes that are associated with the presence of different bacteria.

* *Lactose Tolerance and Gut Bacteria:* * One key gene is called *LCT*, which determines if you can digest milk sugar (lactose) as an adult. If you're lactose intolerant (meaning your body struggles to digest lactose), and you still eat dairy, you might see more of a specific type of bacteria called Bifidobacterium in your gut. This is because when you are lactose intolerant the undigested lactose makes it to your colon where it becomes food for your gut bacteria, which can lead to increased Bifidobacterium growth. * However, just because you have more Bifidobacterium doesn't necessarily mean it's beneficial, it could mean that your body isn't digesting lactose properly. * If you are able to digest lactose, eating dairy will not affect the amount of Bifidobacterium in your gut. * The study also noted that *other types of bacteria* are affected by the LCT gene, suggesting that the impact of this gene on your gut is complex and depends on your dairy intake.

* *Blood Type and Gut Bacteria*: Your ABO blood type, like A, B, AB, or O, also affects your gut microbes, along with your secretor status, which indicates if you secrete blood antigens in your gut mucosa. * The study suggests that people who secrete blood antigens in their gut tend to have higher levels of the bacteria Faecalicatena lactaris. * This bacteria also appears to be a very efficient metabolizer of these blood antigens. * This means that people with different blood types may have slightly different gut microbiomes and might need to take that into account when they make diet or lifestyle choices.

* *Fiber and Gut Bacteria:* Eating a lot of fiber is generally good for your gut. However, the study found that the bacteria Faecalicatena lactaris does not easily switch to digesting fiber. This means that even if you eat a lot of fiber, this bacteria might still prefer to feed on other things, such as secreted blood antigens. Other mucin-degrading bacteria are more likely to switch to fiber when it is available.

* *Gut Microbes and Mental Health*: * The study suggests that there may be a connection between a specific gut microbe called Morganella and depression. This highlights the *gut-brain connection*, meaning that what happens in your gut can affect your brain and your mental health. * The study also suggests that the MED13L gene is associated with Enterococcus faecalis, which may be linked to a higher risk of colorectal cancer.

* *What You Can Do:* * *Consider your genetics:* You can get genetic testing to see if you have some of the gene variations discussed in the study, like the one for lactose intolerance. This will help you understand how your body works and help you make dietary choices. * *Pay attention to your diet:* What you eat strongly affects your gut microbes. If you're lactose intolerant, you may want to consider whether dairy is good for you. You might also want to consider if you should eat more fiber, and what type of fiber would best support a healthy gut. * *Be mindful of the gut-brain connection:* Keep your gut healthy as it might have an impact on your mental well-being. * *Talk to a professional:* The study is complex, so it's best to discuss it with a doctor or a registered dietitian before making big changes to your diet or lifestyle. * *Remember that research is ongoing:* This study provides valuable information, but the authors recommend further research into several of these connections.

In short, this study underscores the idea that our gut is a complex ecosystem that is influenced by our genes, our diet, our blood type and a host of other factors. By understanding these interactions, we can take better care of our overall health.

So glad I am not the only one here interested in personal genomics.

For example; I a FUT2 non-secretor. Understanding this changes my life and my IBD. I also have NOD2 polymorphisms linked to Crohn's and skin problems. Also Lactose intolerant so...

Understanding this led to the reduction of so much of my pain, mental and physical.

I also have a Partial PNP Deficiency but I will let you look that up.

Presence of FUT2 and FUT3 also have very interesting impacts on CA19-9 levels, which affects cancer detection - https://pubmed.ncbi.nlm.nih.gov/23958938/

Yes! I'm also curious what specific changes you made related to your IBD protocols backed up by your genetic predispositions.

what did you change in your diet / lifestyle after you learned about your genetic makeup?

Sorry for the late response.

I want to preface by saying I have some serious health issues that they have not been able to sort out over the last 30 years of my life, and genetically I am a rarity, probably link to my Sami heritage.

For my FUT2 non-secretor status I eat a lot of seaweed and mushrooms. The Fucose in these foods replaces the Fucose I am not secreting in my intestines. FUT2 is a fucosyltransferase. This helps the bacteria attach to the Fucsoe and not invade my gut.

https://pubmed.ncbi.nlm.nih.gov/34151459/

For the NOD2 I just need to be really careful about infections. If it were not fro my FUT2 non-secetor status that protects me against E. Coli infection I would for sure have Crohn's

https://pmc.ncbi.nlm.nih.gov/articles/PMC2924159/

Based on my PUFA genetics I eat a lot of high omega 3 seafoods and no plant oils.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5672832/

But my big problem is that I have a Partial PNP deficiency. So no sugars and very low calorie diet.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7338719/

Those are the big ones.

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