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The tantalizing links between gut microbes and the brain (nature.com)
86 points by etiam on Oct 15, 2015 | hide | past | favorite | 32 comments



So many gut microbiome variables, so many neurologic variables in the brain, so many type 1 errors calling out from the data in seductive whispers "publish me...". While preliminary research is curious, I predict that more medium-term progress will be a result of throwing fecal transplant at many disorders, it will work for a few (like abx-resistant C diff), and it will not work for others even though people will claim it does. and then people will make up biologic stories about how things interact with decreasingly hand wavy (inflammation!) theories that may or may not be practically testable depending on the number of working parts involved. That's how medicine works a lot of the time, anyways.


There's not a single biological system in our bodies that isn't incredibly complex and has many moving parts. How do you recommend researcher investigate these interactions without being able to control for all these factors?


Great question. I think this is why organ systems with (arguably) relatively fewer interconnecting parts and more accessible parts than the brain, for example blood, are easier to research. Not all of the parts will be able to be controlled, and the closest approximations are probably animal models with a few cloned or inducible genetic changes where significant results are not easily generalizable to people. Biology will probably not be like physics or chemistry, where underlying principles are often generalizable to matter under specified conditions, because we can't defineand control the initial context within and around a human, and ethical guidelines ensure that studies are limited to a morally acceptable degree. So we often have to see what works/fails in practice and explain it in terms of what we know, try to fill in the gaps with more research, and see where it takes us in terms of new treatment possibilities. It's a very iterative ordeal.


This is absolutely true, which is why virtually any study around Autism is complicated.

It's virtually impossible to prove or disprove anything from causes to treatments simply because collecting control groups on such a wide spectrum is nearly impossible on it's own.


The Mütter Museum in Philadelphia currently has Einstein's brain on display. With all the controversy surrounding how his brain was stolen against the will of Einstein and his heirs, it would be ironic if all one really needed to recreate his genius was his fecal matter.


The thing is, we already know that the brain influences the gut, but this doesn't seem to be mentioned. All these hand-wavy press releases seem to be saying it's a mystery why IBS is linked to anxiety and depression, and yet there is very good evidence that the HPA axis significantly influences gut motility, absorption and bacteria.

As for gut-influencing-brain studies, they seem to be quite problematic. You basically have a scientist looking at a mouse and saying "he's running around a bit more than usual".

These studies get upvoted quite often here. It's almost as if people don't want to take responsibility for their anxiety and depression...


We detached this subthread from https://news.ycombinator.com/item?id=10392909 and marked it off-topic.


> The thing is, we already know that the brain influences the gut, but this doesn't seem to be mentioned. All these hand-wavy press releases seem to be saying it's a mystery why IBS is linked to anxiety and depression, and yet there is very good evidence that the HPA axis significantly influences gut motility, absorption and bacteria.

Do you have a recommendation for further reading on this? (Specifically, the brain influincing the gut, not vice versa.)

Purely anecdotal: I have a lot of digestion problems, but it is starting to look like I do better when I am able to maintain a non-depressed, non-anxious state of mind over a period of weeks.


>Do you have a recommendation for further reading on this? (Specifically, the brain influincing the gut, not vice versa.)

Try:

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2982.2008....

http://www.researchgate.net/publication/14603941_Stratakis_C...


Can you elaborate on taking responsibility for anxiety and depression? It seems to me that those things mostly just happen without the person actively causing it, so they can not be "responsible" for it.


What I meant was take responsibility for doing something about it. Sure you can't directly control your neurotransmitters, but you can definitely influence them by changing your lifestyle, mental attitude, etc.


Depression is the very thing preventing people from doing those things. You might as well tell poor people that they could make a lot of money through investment.


Yes, you're right. My point is that some people deny that it's even possible for them to do anything to help with their depression, even though the evidence is pretty clear that psychological interventions do help.

I'm not saying that depression is easy to fix, or the person is to blame for it. I'm just saying that factors such as lifestyle, thought processes, etc. influence anxiety and depression.

(edited to better reflect my point)


It isn't really a "perceived difficulty" thing and your comments seem a bit flippant as if a depression is all due to the person's irresponsibility. Like depression is just because someone is just "sad" but a balloon will cheer them up and they'll be right as rain.

As was pointed out in the comment right above this. Someone suffering from depression is often completely incapable of "taking responsibility for fixing it themselves".

Imagine the thought process is more like "Why should I even bother to get out of bed today? I'm a horrible person and don't deserve to be happy. I'd rather be dead than live through another day of this horrible existence of a life." -- and then you come along and say "There's nothing wrong with you. You just need to be responsible and live a healthier lifestyle." Hell, that'd just add on to their overwhelming feeling of self-loathing. Good job.

You think they wouldn't JUMP at the chance to be able to stop being in a constant state of mental anguish and live a healthier lifestyle?


Yes, you're right. I've edited my original comment. I think the issue is more that some people deny that it's even possible for them to do anything about their depression.


Honestly, it sounds like you're backpedaling. I don't mean that to be super critical. There's nothing wrong with changing your position in response to feedback, but pretending that's what you originally meant seems a little fishy. But I may be misinterpreting what you're saying.

To your clarified point, I'm not sure that's really accurate. I've known a LOT of depressed people and had my own struggles. I've never met a depressed person who logically thought there was nothing they could do to improve the situation. It's well established that regular exercise, sufficient sleep, establishing routines, talk therapy, antidepressants, etc. can help with depression. Again, I've never met anyone who suffered from depression and denied those treatments can help. Anecdotal but true.

The problem is that depression is not logical. If you've never experienced it, you really can't understand it. And it's doubly frustrating, because it can manifest itself differently for different people.

I read an analogy recently that I thought was pretty decent. Imagine you are sleepy all the time, just dead tired, exhausted, and you feel like you can never really get fully awake. Now imagine you're talking to somebody who never really gets tired; they're just naturally full of energy. Imagine trying to explain to them what being exhausted feels like. It's not a logical thing. It's not that you think it's a smart decision to stay in bed all day. You're just drained of all energy.

And when you describe what you're feeling, their response is to give you a bunch of solutions you've already tried. Have you tried drinking coffee? Black out curtains? Maybe your mattress is bad? You know when I'm feeling sluggish, I like to get up and do some exercise, that always perks me up!

At that point, you probably want to punch them in the face. They have no idea what they're talking about. If you had enough energy to get up and make coffee – or exercise for christ's sake – you wouldn't be in the situation you are.

Aaaaaaaaanyway, I'm not disagreeing that personal accountability is important. You can't help the depressed person (or alcoholic or anybody suffering from a disease), if they don't make an effort get help. The problem with depression is that making an effort – any effort to do anything – is often the very thing that person is unable to do.

So, people need to be careful discussing "taking responsibility" for depression, especially if they've never had first- or second-hand experience. Despite their best intentions, they're likely to come off looking like ignorant assholes. From your follow up comments, I think it's clear you're not an asshole. :) But I'm also not terribly surprised by danharaj's visceral response to your original sentiment.


First of all, I do have first- and second-hand experience of this, so I'm not talking entirely out of my ass.

Also, there are actually a lot of people who deny any psychological involvement with depression, and you'll see this a lot on forums (including HN). I'm not going to go into more detail, as it will likely just start another flame war, suffice to say it is definitely an issue.

I'm well aware of the difficulty in doing anything about depression, and it wasn't backpeddling. I was just making the point that it is possible to improve depression through making changes. I wasn't saying that it's people's own fault, or they just need to pull themselves together, or anything like that, which seems to be what people somehow implied from my comments.


> Also, there are actually a lot of people who deny any psychological involvement with depression, and you'll see this a lot on forums (including HN).

To be fair, a lot of psychotherapy advocates claim the same thing about physiological causes. This is kind of funny because the first step in a mood disorder diagnosis is supposed to be the elimination of physiological explanations, but in practice that process is often... let's be kind to the GPs/PCPs and say "optimized for time".

Basically, anyone who claims to have the one true solution to depression is either lying or believes a little too much in their own hype. Some are people who got lucky and had their first treatment work wonders (not a typical experience) and now think that everyone with depression needs to try their specific treatment, but a lot are people with a financial, reputational, or ideological stake in people's beliefs about treatment.

On one hand, depression treatment is certainly a case of "you miss 100% of the shots you don't take" [1]. On the other hand, it's also a case of "it is possible to commit no mistakes and still lose; that is not a weakness, that is life" [2].

[1]: popularly attributed to Wayne Gretzky

[2]: Jean-Luc Picard; Star Trek: The Next Generation 02x21 Peak Performance


That's bizarre. We must travel in very different circles.

I've never seen anybody claim there's nothing that can be done for depression. I've seen people say they've tried all of the standard stuff and nothing helped. That's different though. I'm not doubting you, just expressing surprise. It's also possible that our different experiences are due to us interpreting things differently.

Anyway, I don't frequent those types of forums these days, though I have in a previous life. You're probably much more knowledgeable about what's common in them than I am, at this point.


[flagged]


>Yes, and people who have broken legs should just start running marathons. Shame on them for not taking 'personal responsibility' for being unable to run a marathon.

There is overwhelming evidence that stress causes depression and anxiety, and that psychological interventions can help. I'm not aware of any evidence that psychological treatments can cure a broken leg.

>Fuck off.

You might want to read the rules here. Anyway, thanks for proving my point.


>Getting treatment is literally getting help from other people. In other words, it is not doing anything about depression themselves.

Yes, but for it to have any effect, it needs to affect your own brain, so you do need to do it yourself (even though you might get help from other people).

>I'm not sure why you even brought up these 'some people' who are not mentioned anywhere in the submitted link

I was referring to the constant articles being posted/upvoted here that have dubious science showing that gut bacteria might cause anxiety/depression, while ignoring/denying the overwhelming evidence showing that brain influences gut.

>The word 'responsibility' has connotations of duty and obligation. The term 'personal responsibility' as a whole is a dog whistle used commonly in American politics to attack vulnerable populations of people. It is innuendo

I'm just writing a comment on a forum, not a peer-reviewed journal. I have no idea about the use of the term in American politics.

>Is it not at all conceivable to you that you can say something that bothers someone for good reasons?

Sure it is. However when you get angry about something that someone didn't intend, it stifles discussion.


> However when you get angry about something that someone didn't intend, it stifles discussion.

I think we've been having a rip roaring good discussion tho.


> Anyway, thanks for proving my point.

No. Your point is ill-informed, banal, and frankly, just plain offensive. You're incredibly ignorant and I hope you don't interact with anyone who suffers from depression because blaming people with a disease for suffering from that disease because of a personal moral failing is disgusting. You're gross. The things you say are gross. Stop saying them.


You're putting words into my mouth. Nowhere did I say that people are to blame for depression, or that it is a moral failing. I'm simply saying that some people don't believe that they can do anything about depression themselves, even though it isn't really in any doubt that psychological treatments help depression.

Given your angry ranting in response to my arguments, it sounds like you disbelieve the science, so you are in fact proving my point.


> I'm simply saying that some people don't believe that they can do anything about depression themselves, even though it isn't really in any doubt that psychological treatments help depression.

Getting treatment is literally getting help from other people. In other words, it is not doing anything about depression themselves.

Also, even though Cognitive Behavior Therapy is very effective at treating depression, it does not help all depression, which doesn't discredit it but indicates that depression is complex ensemble of disorders that cannot all be treated in the same way. Depression that is resistant to CBT and antidepressants is scary.

It should also be noted that one of the ways depression manifests is as strong feelings of helplessness, intrusive thoughts, vicious circles of reasoning, and a debilitation of executive function which by definition makes people unable to help themselves.

I'm not sure why you even brought up these 'some people' who are not mentioned anywhere in the submitted link and certainly did not come in here to chime in about their deep need to absolve themselves of the crushing guilt that often accompanies the life dysfunction caused by depression. I think you made them up.

> You're putting words into my mouth.

You used the term 'personal responsibility'. The word 'responsibility' has connotations of duty and obligation. The term 'personal responsibility' as a whole is a dog whistle used commonly in American politics to attack vulnerable populations of people. It is innuendo. The words came out of your mouth, and unfortunately once they're out, they are received in other ears. I'll certainly regret and feel embarrassed having told you to "fuck off" in a few hours or so. C'est la vie.

> Given your angry ranting in response to my arguments, it sounds like you disbelieve the science, so you are in fact proving my point.

I'm angry because you touched a nerve and this subject is important to me. It doesn't have anything to do with the particulars of my understanding. You're rationalizing away my anger towards you. Is it not at all conceivable to you that you can say something that bothers someone for good reasons?


Is it conceivable that you bothered yourself by inferring all sorts of things that weren't actually said due to your own biases? I'd say it's not only conceivable, it's way more likely to be correct than the tack you've taken here.


This comment and https://news.ycombinator.com/item?id=10394059 break the HN guidelines egregiously. We ban accounts that do this. Please post civilly and substantively, or not at all.


Blame shifting works both way: some people don't take any responsibility while they should, and some other promptly gives full responsibility to victims.

There's always a payoff to one's view of the world, whatever it is.


Just to clarify: nobody is blaming victims here (see my edited comment). I'm just blaming people who deny the science.


That is a very good analysis and I agree 100% having seen no shortage of both types of people you mention.


or by getting a job!


I get excited about the prospect of a gut/brain connection precisely because it might be another way to address depression.




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