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How the Gut Affects Mood (fivethirtyeight.com)
198 points by sndean on May 19, 2016 | hide | past | favorite | 33 comments

The research going into the gut these days is going to make for some incredible advancements. A research doctor I respect told me that he suspects we have more connectivity between our stomachs and our brains than anyone really realizes. So much of who we are and what we do is centered around how we take in fuel.

Some good news this week for folks who have GERD, or chronic acid reflux, they discovered the cause: http://www.foxnews.com/health/2016/05/17/researchers-discove...

There are well established connections.

About 90% of the neurotransmitter serotonin in your body is produced by enterochromaffin cells in the stomach.

Though this does not directly affect the brain (the brain has it's own serotonine synthesis) it modulates a multitude of responses like blood pressure, body temperature, which, in turn, affect the mood.

Quote from Wikipedia:

Serotonin is a neurotransmitter and is found in all bilateral animals, where it mediates gut movements and the animal's perceptions of resource availability. [citation needed]

In less complex animals, such as some invertebrates, resources simply mean food availability.

In more complex animals, such as arthropods and vertebrates, resources also can mean social dominance. In response to the perceived abundance or scarcity of resources, an animal's growth, reproduction or mood may be elevated or lowered. This may somewhat depend on how much serotonin the organism has at its disposal.

With a lot of human culture revolving around eating meals communally, including as family, or to facilitate diplomacy or business relations and as official decorum itself, and this indeed for millenia I suppose, it wouldn't be a stretch to say that what we've had in our stomachs, has shaped our entire history on this planet.

I'm not sure I follow how a cytokine can be a cause.

Cytokines are, generally, cell signalling molecules. In the case of GERD, if I understand the process correctly, these cytokines are instructing the tissue of the esophagus, and associated immune system cells, to initiate the inflammatory response.

Inflammatory responses in mucosal tissues typically include an increase in mucous production, which is the body's attempt to protect the tissue from the refluxed stomach acid.

So it follows that the first tissue changes you should expect to see are inflammation and increase mucous production as the body tries to protect itself from exposure to stomach acid.

This doesn't mean the cytokines cause the inflammation, nor that they cause acid reflux, they're just the cell signalling molecule that initiates the inflammatory response, released in response to increased acidity on the tissue surfaces, released long before gross changes occur as a result of acid damage.

If we give medicines to dampen the cytokine release, or dampen the inflammatory response to the cytokines, thereby reducing the inflammation, that doesn't mean the tissue won't be damaged by the acid reflux - if anything, down-regulating the normal inflammatory immune response will worsen the damage caused by the acid.

The question is: what is causing the acid reflux?

If A results in B being taken as a preventative measure (to stop Q), and then C occurs as a result of that preventative measure, then the causal graph looks like A->B->C.

That is, both A and B can be said to cause C, in the standard counterfactual sense of the word "cause": if you hold everything but X constant, and add more X, and more Y occurs, then X causes Y.

That doesn't mean you shouldn't do B. If Q is worse than C, it's still a good choice. But it does cause C.

There is a really good book written in 1999 that expounds on your research doctors point (and is written with a very approachable tone)


I have Barrets Oesphagus (caused by chronic GERD).

That is amazing news!.

Link is down?

This article gives a great overview of a fascinating field, and does so fairly responsibly, which is unusual in the popular press.

From the end:

'“Too many large-scale, spurious claims are being made,” Dinan said, mostly by people with something to sell. Although we have “very good data” from animal studies, he said, there’s nothing that could be described as solid clinical data linking the gut microbiome to depression or anxiety in people.'

This research is super exciting. It's also super new. The technology for sequencing gut bacteria on a large scale has only been around in a real sense for about 10 years, and only been affordable for about 3-5. We'll get there, and almost certainly gut flora matters massively for all sorts of biology, but it's important to temper excitable headlines.

> Although we have “very good data” from animal studies...

This is a pretty important thing to keep in mind. There are a lot of studies that I've seen, extending connections to humans from mice [1], even though understanding of the suitability of these mouse models has just recently (or hasn't) been studied [2].

So... "In humans, the data are more limited. Researchers have drawn links between gastrointestinal pathology and psychiatric neurological conditions such as anxiety, depression, autism, schizophrenia and neurodegenerative disorders — but they are just links." [3]

[1] http://www.sciencedirect.com/science/article/pii/S0092867415... [2] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427216/ [3] http://www.nature.com/news/the-tantalizing-links-between-gut...

Absolutely. Humans aren't mice. That doesn't mean mouse studies aren't enormously helpful, but it does mean that we should take things with a grain of salt. The complexity of even a mouse is pretty enormous, and humans are that much more confusing.

As for gut to brain transmission, the first thing that comes to mind is being hangry but that's probably a different thing :)

Why would human guts be that much more confusing than nice guts?

For one, we have twice the number of bacterial species. But it seems more important to me that only 4% of the microbiome is shared between humans and mice.


That second argument does not imply that humans are more confusing than mice, just different.

My reaction was only against the apparently underlying assumption that humans, biologically, are more complex than mice, a remain of the idea that they are more evolved or a biased perspective due to the fact we study them in more detail.

This field feels like it's starting to blow up. I'm seeing lots of studies dealing with gut microbiomes. And from talking to a lab developer I know, it seems like this is largely because computing has become super cheap (think AWS), and the tools have become very power and simple to use (think Pandas and Numpy). He was saying that it's become very easy to find patterns in bigger and bigger sets of sequencing data, that previously would have been inscrutable.

It's not necessarily neurological in nature, but one of my favorite papers in the field in the last couple years shows a potential causal relationship between obesity and gut biomes by using artificial sweetener and a fecal transplant in mice.

Paywalled version in nature: http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...

Unpaywalled version after googling: http://www.drperlmutter.com/wp-content/uploads/2014/09/Artif...

Lactobacillus Rhamnosis - supposedly stimulates the nerve in the gut that then triggers GABA production.


I get it here: http://www.customprobiotics.com/custom-probiotics-l-rhamnosu...


As I understand the anxiolytic effects, it is all about a proper balance between glutamate and GABA [1].

Some people get really stressed out when they eat too much glutamate-containing foods. So, perhaps probiotics can help address the glutamate too (?)

Note: some warnings here: [2] (some bacteria produce glutamate!)

[1] http://www.holistichelp.net/blog/how-to-increase-gaba-and-ba...

[2] http://forums.phoenixrising.me/index.php?threads/why-probiot...

I'd be very interested to hear more about your experience. How long have you been taking them? Have you noticed an effect?

One of the most mind-blowing things I learned about when studying psychology was the theory of distributed consciousness. Basically it goes along the lines that though most of our neural matter is in the head (i.e. brain) there are pockets of it here and there throughout the body. For instance in each of the sections of the spine - highly trained movements are coordinated between these. They are signalled by the brain but motor control can happen largely independently.

One thing that stood out is that the highest concentration of this neural matter is in the stomach. Your stomach does have access to some information about the outside world: Bass sounds, orientation, and proprioceptive activities. But it is largely ignorant of the outside world because it doesn't have access to the main senses the way the brain does. This sits nicely with the "gut feel" lore, where your stomach is uneasy about something though your brain says things should be fine. Your stomach can't be fooled by your senses.

From the article: "there’s nothing that could be described as solid clinical data linking the gut microbiome to depression or anxiety in people"

I went to a conference recently where an MD/researcher in this field discussed the latest state of the art findings.


Long story short, the gut-brain axis is a compelling area of study, but based on the fact that nearly all studies have been in murine models coupled with the relative paucity of human trials, the jury in the medical community is still largely out.

This would be pretty interesting.Considering I'm studying Psychology a bit, this would really be a field to look at. How does it affect whether a user wants to visit a certain section of a site more or not or how does this ultimately affect the development of the GUi in the long run?

Does anyone know any good companies working on technology that identifies and categorizes aspects of the gut microbiome? This is a field I'd be very interested in getting into

I clearly have the mood affecting gut. If i have a sinking feeling in my chest (a devastated one), i immediately have a painful reaction in the bowel (or the gut).

"No guts, no glory" does take on a new meaning ...

Accidentally downvoted you on my phone, sorry.

We detached this subthread from https://news.ycombinator.com/item?id=11732322 and marked it off-topic.

If this was detached, why is it still viewable on the thread?

Detached just means we made it be a top-level comment as opposed to a reply to another comment.

Your downvote has been cancelled out. :)

[insert obligatory 'redesign-HN-to-be-responsive' thread here]

It is responsive since few months now.

Interesting, this answers my question on the last post. It seems that there's still a while to go before we understand the interaction of probiotics and general health.

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