There was a lot of work on microbiome and cancer immunotherapy... the latest study in the field published in the most prestigious journal there is [1] seemed to show that fibre intake was more important than any specific microbe. In fact they found that eating more fibre and taking probiotics resulted in worse outcomes than just eating more fibre alone. This was recapitulated in a mouse model:
> Together, these data have important implications. We show that dietary fiber and probiotic use, factors known to affect the gut microbiome, are associated with differential outcomes to ICB. Although causality cannot be addressed from the observational human cohort, where unmeasured confounders may exist, our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics—with suppression of intratumoral IFN-γ T cell responses in both cases.
It would be a bit disappointing if the final conclusion from all this microbiome work was 'Eat more vegetables'...
Fiber is so incredibly important and much of our food in the West doesn’t have much of it. We see colon cancers and diverticulitis in people in their 30’s and even late 20’s nowadays. This wasn’t the case years ago and it’s not the case in Asian or African countries.
But we don’t think it’s genetic because we see diverticulitis in people from these parts of the world 10 years after moving to the West. It’s thought that these places consume more fiber by virtue of eating more roughage.
Fiber + hydration is so important. You need to keep the waste moving. If it’s slow and hard on the gut lining you end up sounding these tissues opening them to disease.
I've been tracking my food the past couple months and it's pretty eye opening how much fiber I've been lacking. Now taking supplements, but is there a food you'd recommend in particular?
It's silly, especially to admit on this forum, but I found the Hidrate water bottle that tracks your water consumption actually increased my water intake loads as well.
Personally I like to eat sliced green bell pepper, carrots, celery, and tomatoes with lite ranch as both a snack and often breakfast/"desert". Not entirely sure exactly how much fiber you get from any of those foods, but pretty sure the green bell pepper and celery are pretty high in it.
Besides fresh vegetables, I like oatmeal / porridge, freshly cooked with skimmed milk as a breakfast, which is a good start in the day. You can combine it with fresh fruit if you like.
I will for sure check that out. My usual go-to breakfast is Soylent at the moment. My food tracking app (Cronometer) seems to insist it has too much fat, however.
Besides diet Metamucil is great. My doctor has prescribed it to me. It’s OTC so you can get it at any drug store.
You don’t have to use it if you’re getting fiber but if you notice you had a day or series of days where it was low then drink a Metamucil. It’s great.
Make sure to drink lots of water with this, as it has the possibility to glue up your intestines without enough water. To understand why, put a spoonful in a glass of water and leave it for a few hours. You really don't want your intestines glued up!
I’ve been using the Hidrate “smart water bottle” as silly as it sound the gamification really works on my brain and I love feeding more data into Apple Health.
I’ve recently learned I have sky-high cholesterol. Doctor mentioned that eating fiber can sequester cholesterol. So along with dietary changes and exercise he recommended Psyllium husk in water. Apparently this is a great way to increase fiber intake. I bet a lot of people could improve intestinal health by increasing their fiber. Apparently we’re now learning that improving intestinal health can have effects on the mind!
I mention it in the post but it’s about bulking your stool so it moves through your colon. The colon flexes to push waste through and without bulk and hydration it’s difficult to do.
If you have frequent constipation (or even partially regular constipation) or you have to work a bit to drop a deuce then you probably need more fiber.
Wiki says: <<Soluble fiber (fermentable fiber or prebiotic fiber) – which dissolves in water – is generally fermented in the colon into gases and physiologically active by-products, such as short-chain fatty acids produced in the colon by gut bacteria. Examples are beta-glucans (in oats, barley, and mushrooms) and raw guar gum. Psyllium – a soluble, viscous, nonfermented fiber – is a bulking fiber that retains water as it moves through the digestive system, easing defecation. Soluble fiber is generally viscous and delays gastric emptying which, in humans, can result in an extended feeling of fullness.>>
Interesting result about the fiber plus probiotic. To me that’s saying that’s your body mostly knows how to maintain a micro biome if given the right building blocks.
I wonder how the immune system comes into play to actively shape the microbiome, vs our typical understanding of just “fighting bad bacteria”.
a healthy microbiome should be self sustaining. why would it be useful to eat bacteria that is supposed to be present in the gut already anyway. what does make sense though is providing a favorable environment. for that it will be useful to provide certain substances on a regular basis. so, going from microbiome to fiber might make plenty of sense even from the microbiome perspective.
>The finding, which emerged from a study of how genetics and diet affect the microbiome, “is really solid proof that this association could have major clinical importance.”
It seems genetics can play a role in some people having a healthy flora. Maybe their bodies can't convert a certain bacteria from food stuff efficiently, thus they are required to supplement.
Not if you genocide it with antibiotics or your parents or environment didn't have it well in the first place.
People may want to take a fecal sample before starting antibiotics to "reseed" themselves.
Also, it will take time to map and analyze essential and harmful constituent species. Perhaps there will be the equivalent of "vitamin" essential bacterial for persons of particular genetic makeups and diets.
There are specific situations where probiotics can be helpful - antibiotic induced diarrhoea for example, prevention of traveller's diarrhoea is another.
> Why only more vegetables? Isn’t fiber also in some other food?
Fiber is in some other foods, but not at the same ratio of fiber to calories; given that calorie surplus is also a common source of health problems in the developed world, vegetables are generally the best fiber source to add.
Fiber being a type of carb is also found in other high carb foods like beans, whole grains, potatoes (with skin), and popcorn. Beans are the best source of fiber by a mile in terms of quantity.
I don't think I said anything of the sort. Regardless, fiber is food for the microbes in the gut. Eating fiber from a diversity of sources is important as well as quantity.
Black beans, kidney beans, white beans, garbanzo beans, lima beans, black eyed beans.... we can go on if you like. Don't forget the huge variety of lentils as well.
There are two different kinds of fibers: soluble and insoluble. The insoluble one is the most important for your gut and the one in the article. This fiber you will only find in vegetables and fruits, in particular in sturdy ones such as beans, nuts and full grains.
Your gut bacteria are already getting plenty of food, but to digest the food efficiently, they also need something to hold on to. This is the function of the insoluble fibers.
I get my fiber from oatmeal. Simple plain rolled oats, no sugary additives, roast with a bit of olive oil in a pan to unlock their full nutritional potential, then cover with enough water, add salt and let simmer. Consume with appropriate additions as desired, I usually go for plain yogurt.
You wrote: <<roast with a bit of olive oil in a pan to unlock their full nutritional potential>>
I never heard of this technique before. I tried to Google about it, but I cannot find any scientific studies about it. (I found plenty of pseudo science websites touting it.) Can you point to any scientific studies about this technique?
Just another data point, but my journey through digestive issues and recovery was kicked off by the worst depression and burnout I ever experienced, which started in 2019 and lasted 3 years.
My best guess for what happened is that work stress, excessive celebration and coping with the cognitive dissonance of the pre-COVID era and subsequent pandemic, combined with overtraining and the misuse of protein shakes in place of food, left me in a chronically dehydrated state. The body tries to collect moisture from the gut, which opens an opportunity for bacteria to get into the body cavity and blood, which is colloquially called leaky gut. This sets off food sensitivities and eventually an autoimmune condition/response to lectins, gluten, etc, which have proteins similar to linings in the body, joints and thyroid. Then a cascade happens where everything goes out of whack quickly. In my case, I went from being in the best shape of my life, the strongest I had ever been in the gym, to barely able to get out of bed in the morning. In other people, it might present as chronic fatigue, arthritis, etc.
I didn't really believe any of this in 2018, and my meal plan then consisted entirely of everything that I can't eat today. So I consider what people say politely, but for the most part, they have absolutely no idea what they're talking about. This experience has made stuff like GMO foods sound absolutely insane to me. Like, why would we ever taint our food supply to make food 5 cents cheaper or "feed the world" when we've been operating under artificial scarcity since the end of the second world war? It's all a crock.
Every time you eat inflammatory food, the risk is similar to smoking a cigarette. Probably nothing will happen, but if it sets off your immune system, you may wake up one morning chronically depressed and/or unable to eat something that you rely upon. It got me after I turned 40, YMMV.
> I didn't really believe any of this in 2018, and my meal plan then consisted entirely of everything that I can't eat today.
I suspect you had the same degree of confidence in your understanding of these issue then as you do now. It's interesting that you can reflect on your overconfidence in the past, but don't seem to express any skepticism regarding your current beliefs surrounding nutrition.
By the way, I'm not saying that you're wrong! GMOs may be bad, but I think you would do well to level some degree of skepticism over your current understanding of nutrition as you do toward your past understanding. Consider that perhaps you will be here in 2026 telling us about how you got it wrong today.
There's an asymmetry in the risks associated with choosing either a) to restrict or b) not to restrict the set of foods you eat.
Overconfidence in (b) carries more risk than overconfidence in (a). The set of chemicals that are toxic is much larger (as in >>>) than the set of chemicals that are necessary for sustaining life.
The set of nutrients that will cause some kind of problem if missing is actually pretty large; consensus dietary advice usually includes the keyword “varied.”
I'm sorry to hear about your experiences and it sounds like you learned a lot from firsthand knowledge. But, respectfully asking, what does inflammatory foods or poor eating habits have to do with GMO foods?
1. Genetically modified (GMO) foods can cause non-food compounds to get synthesized in the food that our bodies have never seen before, which can trigger autoimmune issues. I consider this the lower risk.
2. GMO foods are designed specifically to allow more use of pesticides and herbicides. These get incorporated into the food and can stay around after washing, especially in processed food. Pesticides are low-level neurotoxin and disrupt gut nerves, while herbicides disrupt gut flora. Loosely, what happens is that the body is sensitive to most plant husks, since they are designed to keep bugs out that feed on them. GMO copies that defense mechanism, often amplifying it hugely, resulting in amplified food sensitivities. I consider this the higher risk, so high in fact that the consequences of it can be life-altering.
Edit: These effects combined turn ordinary food into inflammatory food
My impression is quite the opposite - GMO insect-resistant plants enable using much less pesticides (the savings from reduced frequency and quantity of pesticides being the economic reason for choosing such crops) than non-modified equivalents.
GMO roundup resistance allows us to use a bunch of herbicide without killing the food crop. This seems to indicate that we’d be using a lot more roundup on those crops than otherwise.
This article [0] points towards the reality being somewhere in the middle - more herbicides but less insecticides.
> GMOs have been changing the way that pesticides are used in agriculture. Herbicide-tolerant genetically modified (GM) crops have led to an increase in herbicide usage while insecticide-producing GM crops have led to a decrease in insecticides.
Not OP. In many cases, the genetic modifications are either performed to either let the plant produce (more) lectins that kill insects, or make the plant immune to certain herbicides like glyphosate. The human gut and microbiome might be able to deal with lectins they have evolved to deal with, and in “normal” quantities. But those additional GMO lectins are suspected to be hard on the intestinal barrier. If that barrier is compromised, autoimmunity might be the result, as OP indicated.
This is exactly the problem. The idea of GMOs is fine, but if it's increasing the load of gut damaging chemicals in the food supply that is not good. And the truth is we simply don't know, so it's crazy to just assume that these GMO foods are gut safe. These days it seems everyone I know has some kind of gut issue (myself included), so I think we should be cautious with GMOs.
Also why would GMO be bad? The criticism comes mostly from people that also believe in osteopathic / homeopathic medicine in my social circle.
I find it a terrific chance for humanity to engineer plants in such a way that they are more robust against disease and bad weather (with CRISPR/CAS and such methods).
Here is my criticism of GMO foods; or at least, the reason I'm wary of them. I don't believe in any "woo" at all.
Why would the massive corporations that have driven the food in our supermarkets ever cheaper, ever thinner in nutrients, ever higher in fat and sweeteners and fillers, ever more laden with pesticides and antibiotics, ever more processed—why would they use a technology like GMO crops for good? Why wouldn't they just splice pesticide and sugar genes into them directly and juice the yield even harder so that the soil is stripped and ruined even faster? I think they will be used to boost profits, not make our food more nutritious, or even cheaper in any way except per calorie.
I understand there are potentially benefits, e.g. growing crops resistant to pests so that spray pesticides can be reduced. I just have no faith whatsoever that these kinds of considered actions will be taken, based on the last 100 years of technology. It's just going to be wheat and corn, wheat and corn, wheat and corn until caloric yields approach insolation and the soil is as gray and lifeless as the moon.
The risks from unknown unknowns are even worse with genetic engineering in crops, due to the inevitability of hypothetical "harmful to humans genes" propagating from one population to others by pollination.
Currently there doesn't appear to be any evidence that GMO is bad for your health and most GMO is just transplanting genes from other edible organisms.
Hopefully regulators aren't going to allow insertion of engineered genes producing novel molecules without going through actual medical grade trials for those molecules. Or it may torpedo the entire industry.
In every case of GMO food I have encountered, the compounds are not novel. Rather, they're an adaptation or resistance found in one species and transferred to another.
I don’t think GMO is necessarily bad, but while companies are working on ways to make plants more robust, I doubt they’re taking the long term effects on human health into account.
In theory, there are lots of fine things we could do with GMOs. In practice, basically the only common use of GMOs is to allow indiscriminate use of pesticides and herbicides. This is purely about profit for chemical companies, without regard for environmental impact. I don't care to eat more pesticides and herbicides, either.
Nature produces both edible products, inedible products, and toxic or partially edible (tomatoes, potatoes, etc.) products. AFAIK, there is almost no risk in transferring genes from one edible non-toxic product to another edible non-toxic product. For all other gene transfers, testing is required.
"AFAIK, there is almost no risk in transferring genes from one edible non-toxic product to another edible non-toxic product. "
And where is your knowledge coming from?
I am certainly not a biologist, but as far as I know, there are quite some plants that are edible in the breed we eat - but a different wild form is toxic (carrots for example). How are you sure, the wrong (dormant) genes do not get transfered and activated, without testing?
Or even with the same plant, potatoes. The root is good for us, but the flower is toxic.
In other words, you always have to do extensive testing, when you play around with genes.
Genes are not computer modules you just swap around and turn on and off. It is way more complicated.
Are you implying oranges and bananas were made with modern GMO methods?
I agree that the anti gmo/vaxx etc. crowd is quite irrational in many regards, but I can see a difference between traditional breeding plants - and directly editing DNA.
Yes - and this is also what happens in nature all the time. Only slower and random.
And surprise: many plants are poisenous.
And even with the slow method of natural breeding, poisenous traits can creep back in. The potential and speed of GMO methods is just way higher. For good and also bad results. So it is not the same.
Right, and GMOs are much more targeted engineering. It's the same bs of "we don't know the future side effects in 30 years" scaremongering of anti vaxxers.
Just like with vaccines having plenty of resistant food so people don't starve far overvalue whatever little side effects you might get.
I bet you two are the type who smugly told everyone off for believing the "completely disproven" lab leak theory for a year, before never mentioning it again.
I'm not into osteopathy or homeopathy but my concerned about GMO are because I don't trust that the scientist really know what they are doing, or can fully understand the impact any changes they might make, not only on humans, but on the environment at large. Nor do I trust our government to be able to police and regulate the industry. Nor do I trust big farma to put health before profits.
I think humans always genetically "engineered" plants by selection process.
Our current cultivated plants are the result of thousands of years of breeding.
Who knows what accidental genetic damage from breeding will cause problems in humans?
Harmful crop breeds would have been selected against over the course of many generations, right? Now we're doing it on a larger scale, so the risks and rewards are greater. What is our knowledge of the risks and rewards? Are the rewards aligned with general human wellbeing, or just a profit motive? I don't know.
I must have missed the announcement that we had worked out exactly what causes food allergies and intolerance and have promised not to do anything that could trigger them when doing GM.
One of the modifications some GMO plants have is to produce more/more effective lectins to make them more resilient against insects. Given research on lectins shows many of them are harmful to human health, it seems like a valid concern.
As just one example, if you live in an area where it is difficult to get dietary Vitamin A, you might enjoy the benefits of not going blind due to Vitamin A deficiency by eating Golden Rice[0].
Have you ever eaten a SweeTango apple? It is one of dozens of varieties that have been created in the last hundred years using genetic engineering via cross breeding[1]. Do you know why commercial tomatoes are so bland? Genetic engineering via selective breeding[2].
The fact of the matter is that all of the crops and livestock that we cultivate today are genetically engineered. The main distinction now is that we are technologically advanced enough to introduce beneficial modifications deliberately, rather than relying on random mutations and gene recombinations that occur in nature at random over hundreds or thousands of generations.
It boils down to cost in the same way that you and I not owning a private jet boils down to cost—which is to say, as nice as it would be, there are probably not enough resources on the planet to feed everyone a balanced diet without these continued advances in food production, as the current conventional farming practices are not long-term sustainable, and they are already required to actually feed everybody on the planet today.
> Genetic engineering goes way beyond the possibility space of selective breeding, which we have thousands of years of experience with.
And inside that possibility space are things like extremely high-yield crops that end hunger forever. Grains like Golden Rice that solve nutritional deficiencies caused by incomplete diets. Nuts that are modified so they don’t trigger life-threatening anaphylaxis. Crops that absorb and sequester CO2 more efficiently. Delicious new hybrids that don’t even exist right now. Foods genetically modified to be low in FODMAPs so people who have gut problems aren’t so restricted in what they can eat.
All the problems that exist now with diets have hypothetical solutions in genetically engineering crops to create more of the nutrients that we need to be healthy, and to eliminate the bad stuff that makes us sick, down to the point of being able to provide ideal nutrition for a specific person’s body. However, we’re unlikely to get there if people’s imaginations are always focused on the potential negatives instead of balancing those risks with the obvious potential and need for this sort of technology to be developed.
A liveable Earth? Look up "nine planetary boundaries". The "biogeochemical boundary" especially pertains to the nitrogen and phosphorus cycles, both necessary to plants. Nitrogen- and phosphorus-supplying fertilizer is energy intensive to produce and toxic in wide-area run-off. Some crops live in a symbiotic relationship with nitrogen-fixing bacteria, so scientists are actively researching ways of engineering that abiility into other crops -- which would greatly reduce the need for producing fixed nitrogen for fertilizer, which, in turn, would greatly reduce the need for the high fossil-fuel-consuming method of generating fixed nitrogen for fertilizer, thus helping out on the global warming front. It's not all about cost.
I only made it very recently. I had tried absolutely everything and gotten almost nowhere. I finally stumbled onto everlywell.com tests, took the comprehensive test of 200+ foods, and discovered almonds and dairy were the main culprits. I would ave been very unlikely to eliminate almonds as part of an elimination diet.
Anyway, once I was able to feel better again, even for a day or two, I then was able to try other changes along the decision tree in the problem space. It soon became obvious what caused what. Everlywell says that 18 months of avoidance can often allow us to eat foods we're sensitive to again. I've blabbered about it at length in my previous comments, probably too much haha.
What you have described is EXACTLY what I have been experiencing myself over the last year. This is the first time I have ever seen my symptoms and trajectory laid out like this anywhere, it’s truly surreal. Words cannot convey how much I would appreciate any help finding treatment. I’m honestly nearing the end of my rope dealing with this with no end in sight. I’ve lost 30 pounds of muscle and I’m currently too sick to work anymore. My doctors have been useless and basically clueless.
Oh man, sorry to hear that. Here are some more data points about what I was doing in the 6 months before I got sick that might help:
* Glutamine every day for "gut health" (not the culprit, but I think I was self-medicating without realizing it)
* Animal Flex joint supplement (not the culprit, but I think that I was using the glucosamine-chondroitin component to heal my inflammation and gut lining so joint pain relief was just a bonus)
* Zinc gluconate multiple times per week or every day (not the culprit, but I had heard that ZMA was good years before and noticed a good bump in my workout recovery)
* Whey protein powder (almost certain that this was not the culprit, any brand, but the ones containing casein are hard on me and may have set off my initial digestive issues)
* BCAAs (almost certainly not the culprit, any brand, this is the best recovery aid that I've found after whey if taken immediately after a workout)
* Pre-workout (almost certainly not the culprit, any brand, but my burnout did coincide with drinking up to 3-4 cups of coffee some days at work and then a pre-workout at night before the gym)
* Bean burritos with onions and peppers every day (main culprit, I think that my food sensitivity to legumes coincided with S&W discontinuing pinquitos sometime around 2015, then I switched to pinto beans which are much harder on the gut and almost certainly GMO today, I see that S&W has pinquito heirloom beans on Amazon now that I'll try)
* Whole wheat bread (main culprit, I'm unable to eat several whole grains now, even oatmeal, unless they are gluten free, I believe that herbicides in the husk triggered it and that everyone is vulnerable to this one)
* Almond butter (main culprit, I was trying to eat less meat and it backfired spectacularly, see the Vertical Diet by Stan Efferding to learn how diets go wrong in the health and fitness world and leave older lifters only able to eat ground beef and rice)
That's all the physical side. I realize now after going through a healing and growth process during the pandemic that I had multiple opportunities to correct my course, but I ignored them before I was "woke":
* Due to multiple traumas over the course of my life, I had learned to turn off my feelings entirely (main culprit, I just took it and it in many jobs and relationships, without communicating or setting boundaries)
* Even when under crushing feelings of burnout, which I now realize is severe anxiety and a shut down response when the mind and body don't know what else to do, I forced myself to keep going to work and the gym (main culprit, I needed rehab on my injuries and nutrition before doubling down on more work)
* I didn't go to the doctor, because I was embarrassed that I let my life get so out of control, so I just worked harder and harder and ignored my health (main culprit, my life had become the movie Bright Lights, Big City and I was putting everything off indefinitely)
Writing this out, it's almost kind of funny because it would be easy to diagnose someone if they came to me with this list. The main culprit for me seems to be that I didn't prioritize my health, like ever, until it failed. Keep in mind that my work capacity at this point was tremendous. I was working 40-45 hours per week and going to the gym 5 times per week for massive 1.5 hour split workouts and eating 4000+ calories per day. I started breaking out really bad and getting joint paint and GI distress, but just kept acting like everything was normal.
If anyone is in this boat and their health isn't working anymore, I'd highly recommend a full reboot, getting away for a few weeks and setting your ego aside. Meditate on your specific injuries and identify what's hurting in the body. Then address those injuries directly. You might need to go to a holistic or eastern medicine specialist because western medicine often misses secondary or multiple causes. I'd prescribe:
* Take 2 weeks off from work, gym, and other obligations like family
* Drink the maximum amount of water per day you're allowed, and give your kidneys and other organs a rest (at least a gallon)
* Abstain from all supplements, possibly even a multivitamin (listen to your body's cravings and feed it what it needs)
* Switch from nutrient-dense foods to nutrient-sparse foods, so eat leafy greens instead of peas, pumpkin seed granola instead of eggs, baked chicken and rice instead of steak, etc (stop stoking your boiler for a while so it can heal)
* Get your testosterone, thyroid and other hormones checked (that much muscle loss sounds hormonal, also, my weight has fluctuated that much and it does come back in a few weeks/months so take heart that it's probably going to be ok)
* Move your body for the sake of movement, do stretching/yoga, dance, or just walk (spirit communicates with our reality through movement, that's how reading signs and Tarot work, I added this because lack of woo-woo is what made me sick because I was dead inside)
Edit: one last thing was ashwagandha, I took it for 3 months recently and it seems to have repaired something with my digestion and took my mood from a 2-4 to a 7-8 consistently with no other changes. I still have the afterglow of the energy boost a month after tapering off and stopping. If anyone does this, be sure to check in with a friend or doctor so that you don't accidentally take it too long and hurt yourself.
This was a _fascinating_ read and I thank you for writing that all up - I'm in your "3 year" dip and in the past made attempts at tackling the gut biome issue with cycling probiotics, fresh vegetable fibers, organic/local yogurts, staying away from fake sugars and other dietary things that blow out the biome and even after a few weeks of doing this I never felt any better - would shrug my shoulders and go back to not really caring.
Was there 1 inflammatory food item that is like kryptonite to you now? Fake sugars? Wheats?
Same age as you. I've recently got diagnosed "leaky gut" / auto-immune reaction as well and had food intolerances discovered. Mainly milk / nuts / eggs / grains / beans. Happy to talk and exchange insights if you like.
Inflammation is a necessary function of the human body. There are no anti-inflammatory diets[2]. Short term inflammation has no bearing on health markers[3].
Just focus on a diet rich in whole foods, mostly plants that you can stick to over the long run.
Great to see the gut brain axis becoming more well known in medicine. Less than 10 years ago it was considered near pseudoscience to consider that the gut could actually influence the brain.
I went down that rabbit hole to have a more informed opinion and I found that accepted science would converge on some of the same goals naturopaths and other alternative medicine practitioners eventually.
Basically, they both want personalized medicine. As in, remedies that are custom tailored to the internal state of the individual, instead of “personalized” by listening to an individual describe a current ongoing affliction.
Alternative medicine lacks any method for peer review or repeatability and practitioners themselves procedurally generate the remedies, which makes it incapable of being accepted science except by mere coincidence of some practices eventually being peer reviewed if reviewable at all. This is by a design that is comical to the scientific community, where “everybody is different”.
At the same time, the scientific method and peer review itself is too rigid to evaluate all ailments, without associated advances in technology. This is also by design as it was necessary to distinguish the sciences from arbitrarily religious or arbitrarily heretical practices at one point in some areas.
Now we are on the cusp of convergence of the ideals, by being able to analyze and sequence the symbiotic relationships within our bodies. How little control we have in many cases, or at least potentially redefining the sense of self.
At the current pace of research and studies, when do you think we could expect to see something come to 'market' that could be used - first as a diagnosis and then as a treatment/medication/technique.
As someone with IBS - right now I feel like there is no clear 'problem' defined for it. You are just categorized by the doctor (Rome 3 or whatever) and people go through various tests, medications, non-fda approved stuff to see what works.
I am eagerly looking forward to some progress in this area to hopefully fully understand whats going on and get a proper diagnosis
There are a variety of strategies being pursued to make pharmaceutical products out of microbiome research. Broadly those are:
1: "bugs as drugs" - genetically engineered microbes that perform some function. The idea here is that having the microbe in situ performing some function will be a much better way to administer a particular compound (or set of compounds), or remove a compound, than a traditional pharmaceutical. Large pharma companies have studied phenylketonuria as a metabolic disease for which the bugs as drugs approach would be great. Find a microbe that consumes phenlyalanine at a high rate and administer it at high levels (or get it to stably engraft in the host) and you have a treatment that would be vastly better than current dietary regimes.
2: "community engineering" - this takes many forms from fecal transplant, to trying to engraft a certain small cocktail of strains, to altering what the in situ community is doing by feeding a probiotic. The idea here is that there are tens of thousands of metabolites that microbes are producing in the gut, and by balancing or tailoring the set of metabolites that are made, you can improve health. Fecal transplants have good data for clearing recurrent C. diff in phase III clinical trials - this is the best developed of the microbial therapeutic strategies currently. Everything else is phase I or before.
3: "microbial natural products" - this is the world I work in (shameless self-promotion - if you want to come work at a very early stage microbiome startup email me at will@interface.bio). The idea here is to find the particular chemicals/metabolites that microbes make that have positive influences on our physiology. Most research here is focused on immune conditions, metabolic syndrome/dietary stuff, though there is increasing interest in depression and other conditions.
At a broad scale, I would say it will be 1-2 years before fecal transplants receive approval as a therapy for recurrent C. diff infection, at least 5 years before a bug-as-drug will be available, and at least 7 years before a microbe-derived natural product is on the market as a pharmaceutical. It takes an incredible amount of work to get from these associational studies to a pharma-grade product.
In the interim, I think there will continue to be a bunch of diagnostics and probiotics companies that (IMO) are bordering on absolute nonsense. There is very little predictive value to the tests supplied by most of these companies, and the data on probiotic efficacy is bad in humans. There is good evidence of probiotic and prebiotic effectiveness in animal husbandry (e.g. fish and livestock) but the data just aren't there in humans.
Thank you, appreciate the breakdown. With so much focus on the gut research recently I feel like we are on the cusp of bringing together lots of things and new understandings and that hopefully happens soon
Had a great doctor that helped me get started, after many that did a shoddy job, and this has been my experience as well.
Very much a 'seems like IBS, try low FODMAP, see what works and doesn't via experience,' which was pretty amazing/alarming how little is understood about our guts.
I'd love to know when the science is going to start catching up. Especially since I think it'll be interesting to find out if something has been added to our diets that's causing an increase in intolerance over the last decade+.
I recommend you check out the app from Monash [1]. It’s a paid app but really worth it and its been incredibly helpful for me (I say this as a user, not affiliated with them). AFAIK it contains the largest number of tested foods and they keep adding new foods and retesting and updating older food quantities and list out the specific fodmap associated with each food.
From what I have found online, every other source is either outdated or mostly copies the data from here.
ICYDK (From the studies I have read online) Researchers from Monash were the first ones to identify low fodmaps and they continually release research studies in this area.
To answer your question about chickpeas - right now I see 2 different tested versions in the app - one is Canned chickpeas - this says quarter cup (42g) should mostly be fine but half cup (84g) contains moderate amounts of Oligos-GOS (one of the fodmpas).
Green bell peppers - 52g should be ok but 75 to 80g contains high amount of sorbitol.
The app uses a traffic system (red, blue, green lights) to indicate the quantities
Another vote for the app. We've recommended it to others as well. (Only one of my doctors, the last, recommended it to me. I assume the others didn't know about it. All have been family medicine/general practitioners.)
What eventually got me is that certain foods which were listed as low FODMAP were also trigger foods for my symptoms.
So if it doesn't seem to be working, there may have a similar issue.
> Very much a 'seems like IBS, try low FODMAP, see what works and doesn't via experience,' which was pretty amazing/alarming how little is understood about our guts.
Yes exactly this.
> Especially since I think it'll be interesting to find out if something has been added to our diets that's causing an increase in intolerance over the last decade+.
One thing I read is that western diets severely lack in fiber which usually leads to loss of microbiome diversity [1]. But studies like this are still early stages, we need targeted results based on all this to really have any effect.
I don't have much knowledge on supplements or even diet - beyond it's intersection with the microbiome. From the microbial perspective I think traditional dietary stuff is enough - eat fibrous plants and legumes and that's all you need to do.
In your opinion, what is the best study that shows direct evidence that changes in gut flora can change health outcomes (preferably something that is a randomized control study). The only area I feel comfortable that good data exists is in the setting of fecal transplants for refractory clostridioides difficile infection. Thanks.
In general we only have mouse or other animal data for other indications.
There are retrospective analyses of patient cohorts receiving anti-PD1 or anti-CTLA4 therapies which have identified certain microbiome states as supportive of those therapies. I believe that these are probably real effects, though I don't think the particular microbes matter - instead I think it's the metabolites they produce and how those influence resting immune state (https://www.science.org/doi/10.1126/science.abf3363 - but you can find many more).
A paper I really like shows that a specific protein from a common gut microbe (Akkermansia muciniphila) confers resistance to diet induced weight gain, insulin insensitivity, etc. (https://www.nature.com/articles/nm.4236).
In general, I think the majority of microbiome work has been associational and demonstrative of the kind of hypothesis-free science that is prone to all sorts of statistical artifacts and misaligend incentives between truth-finding and paper publishing (garden of forking paths, file-drawer effect, etc. etc.)
How strong is the case that zero calorie sweeteners actually cause harmful changes to the microbiome that are linked to depression or other conditions?
Weird question perhaps, some research suggests that bacteria source nutrients from the cell lining in the gut if there is an absence of sufficient nutrients from the food coming into the digestive system. (example: https://www.cell.com/cell/fulltext/S0092-8674(16)31464-7)
That made me wonder what the triggers might be, since the studies see the corroding effect appear in diets deficient in polyphenols/insoluble fibres. At what interval do microbes need nutrients and is simply eating a highly-processed snack that has nothing much to offer bacteria in the gut a possible trigger in itself?
Fascinating question - and not one whose answer is known.
Fiber is good for microbes merely by the virtue that humans lack the glycan-degrading enzymes that are necessary to break it down, so it reaches the colon intact where the microbes can eat it. Humans can digest starch (though it can be physically and chemically modified to be harder to digest) but not the hundreds of other types of fibers that are found in a traditional diet.
I think there is good research that shows that higher fiber diets are associated with lower risk of developing a range of metabolic and immune pathologies, but the particular mechanistic linkages are so subtle that it will require absolutely massive studies to identify them. In general, we know that humans used to eat a much higher fiber diet (e.g. the Hadza people eat 70-150 grams of fiber a day), and we believe that produces a much healthier microbial composition.
The paper you cited is really interesting! I haven't read it - but the overall idea that the mucus lining of the gut can be degraded by microbes who are sourcing carbon, energy, and nitrogen from it is well established.
I think there is consensus that some amount of gut barrier integrity is due to microbial signals. This occurs in two ways - 1) our epithelial cells sense microbial products (proteins, carbohydrates, etc.) and respond by tightening the junctions between them. The overall idea being that you want to keep the bacteria in the colon, but you must balance some level of nutrient flow. 2) The goblet cells which produce mucus in the gut, respond to microbial signals to increase or decrease their mucus production.
There is a lot of research going on trying to understand how certain diets cause defective mucus production and in turn how that can allow microbes to get to close to the epithelial lining (usually the mucus is ~100 microns thick) which results in inflammation.
Recent evidence of another function of microbial activity in the gut of hibernating animals. In short, it appears that they help the host supply enough nitrogen for maintaining muscle mass during hibernation: https://www.science.org/doi/10.1126/science.abh2950
How much evidence is there of long-term effects of these types of treatments? Do you or other researchers in the space ever worry that you are in a sense curing the effect and not the cause (family and societal problems as I understand it), which would imply that efficacy would fall over time? Would sustained fecal transplants, etc. even work?
Is there a good way to test one's own gut microbiome? To determine how healthy it is or isn't, and to track how it changes over time. Basically I want to be able to tell how my diet and things like antibiotics affect it.
I think it's really hard - we don't know what a healthy state of the microbiome is. There is likely a lot of individuality, what is healthy for me is maybe not healthy for you. This probably has to do with early life immune system development and what we were exposed to as kids.
At a high level we know that diversity of microbial species in the gut (but for instance, not in the vagina) is linked to better overall health state. Is this because of the microbes? Probably not, it's probably that the microbes are a sensor/responding to an overall healthy diet/ecosystem.
In general, there are commercial services to track your microbiome and they are interesting from a data perspective, but I am not sure you will get much health information out of them.
We know the answer to a healthy diet - there are no microbial talismans - but it's just not sexy. Eat lots of plants, less sugar, and exercise. I wish it was as easy to follow this advice as it is to write haha.
How about the mainstream explanation? Energy used to be scarce, so high-energy foods tasted good. Now we have plenty of energy-dense and tasty food-like stuff without the actual nutritional content.
Thanks a ton - super curious research. What determines if individuals get Morganella and Kiebdiella bacteria? Is it genetic or can it be impacted by the food we eat?
What is the mechanism of how these bacterias interact with the brain through the enteric system?
We know that microbes colonize the gut in a somewhat predictable way as a function of age. As a newborn your gut is largely dominated by Bifidobacteria, and this slowly transitions to a more complex community over the next several years of life. Events like early childhood antibiotics, malnutrition, other disease, etc. can alter this trajectory. Interestingly this kind of ecological succession seems to be driven by an interplay of both immune maturation (as your immune system matures it starts being more selective about who it tries to let in) and by chemical processes. The gut becomes more anaerobic as the number of bacteria increase (and transition away from the Bifido dominated state) and that has a strong selective effect on the microbes that will grow well.
For specific commensal bacteria we know some of the mechanisms of colonization - there are particular genetic programs that bacteria turn on when they sense they are in the gut to enhance their ability to be retained and not washed out. These programs include physical attachment, motility, and chemical signalling to try to dampen the local immune response.
Pathogens are extremely good at getting in to the gut despite our best attempts at keeping them out. Salmonella typhimurium is notoriously adept at colonizing the host - the infectious dose you need is maybe 10 microbes taken orally in a susceptible host (compare that to 10 billion microbes/capsule in a probiotic).
For these specific bugs I don't know that much. I am excited to read more.
Can we actually do more than correlation yet on this very topic? I always see studies and articles that promise that gut health can solve depression. But I think this is bullshit. Depression is a protection mechanism from your brain and I would bet my ass that the causation is more depression => bad gut health. I would be very interested in your thoughts on that.
Regarding your advice on eating plants, do you know if it matters wheter they are cooked or eaten raw? I mean, is one preferable over the other, from a gut biome perspective. By the way, thanks a lot for your answers!
Far from being an expert on the subject, but I read a paper that said that eating raw vegetables would usually increase the degree on inflammation, but cooked vegetables had the opposite effect.
Potential correlations between gut serotonin and morganella levels? Leading to the question "Can SSRIs affect depression through mechanisms in the gut?".
Absolutely - the chemicals that microbes make in the gut pass into your blood stream and from there access the entire body. There are mechanisms the body uses to ensure these chemicals are detoxified (phase I and phase II metabolism in the liver) and that they are excreted if they reach too high a concentration.
More locally, the enteroendocrine cells (https://en.wikipedia.org/wiki/Enteroendocrine_cell) that line the gut translate much of the internal nutrient state of the gut up to the brain to tell you things about if you should eat, etc.
There is a lot of research on how we could alter satiety by finding the right language that these cells use. There are approved drugs on the market that mimic the activity of these cells (incretin mimetics) to reduce appetite/weight control.
I've seen these studies time and time again. I do wonder what are the practical steps one takes to "repair" or "renew" their gut? I'm not a fan of drugs being the cure. In fact, I don't think they are the first solution people should hope for or supplement with unless it's not practical to get them in a natural way.
I feel like we see more and more gut related issues due to depression & depression's little cousin anxiety. IBS for example manifests itself from anxiety and can also be a gut microbiome imbalance.
If there are more and more studies around gut health being a sort-of panacea of mental & physical health, why aren't we focusing on making healthier decisions for our diet, exercise, and mental well being?
It's no surprise that many people(myself included) in our always connected world suffer with crippling anxiety from over stimulation/shock & awe news/comparison to others/overwork/etc. That anxiety manifests in your gut as digestive issues. Those digestive issues make you less likely to exercise for long periods of time or even at all.
In my opinion, it's four main things. Increase sleep, improve/wide ranging diet, moderate exercise, and reduced stress. There are definitely hacks like fiber, yogurt, sauerkraut, and more that people swear by, but I am genuinely curious if a study had tracked some of these variables to see if they improve gut microbiomes.
It seems to be a case of lots of variety in your diet, ideally lots of different vegetables, nuts, pulses etc, and cutting down/out highly processed foods. Variety seems to be the spice of life, quite literally.
I've just finished reading Prof. Tim Spector's "The Diet Myth". The book's title is a little hyperbolic, but it works through all the major food groups and how we eat and talks about both the historic research and diet fads of the past (like Ansel Keys research that sparked the obsession with low fat foods) and how all these different foodstuffs tie into our gut bacteria, which in turn affects us.
Tim's "thing" is the human biome, but I didn't read it as him touting it as a cureall, but as something that is more important than almost all of us are aware, and which has been seriously neglected to the point that it's having an impact on many aspects of our health. He's also pretty open that a lot of this is still very much up in the air at the moment, and lots more study is needed to really understand many of the effects. He also seems pretty sceptical of the medicallisation and the obsession with isolating one factor and packaging it up as a supplement or magic pill that will solve your health issues.
> what are the practical steps one takes to "repair" or "renew" their gut?
Look up nutritionfacts.org and read/view it with a generous pinch of salt.
A few years ago it took me half a year to switch to a mostly WFPB diet advertised there and I had no issues whatsoever. My gut is now more resilient, I remember having problems with bloating and/or diarrhea if I ate just a bit more fiber some days.
> why aren't we focusing on making healthier decisions for our diet, exercise, and mental well being?
The answers are there, but cognitive dissonance prevents us from recognizing or accepting them.
You could try an isolation diet. Just pick one basic food, such as steak or baked potatoes only, with no toppings except for maybe salt. And eat just that thing for a week or so. Then see how you feel after your gut adjusts. Then gradually add things back into your diet or start with a different food from square one. Not the easiest plan to implement by any stretch, but it's very effective as you're limiting confounding variables for figuring it out.
> what are the practical steps one takes to "repair" or "renew" their gut
It was already mentioned in other threads, but you can find valuable insights in the AIP (autoimmune protocol) diet.
Its main principle is that you first eliminate as many foods as possible that are known to cause issues for people (e.g. due to inflammation, autoimmune response) and then you slowly introduce more foods and see how your body reacts.
I recently started following a similar approach in order to try to address some health issues and also to learn more about my body. In my case I'm leaning more towards the carnivore diet with occasional additions of foods allowed in AIP.
In case anyone is curious about the carnivore diet, I found these YouTube channels to contain good content on this topic: KenDBerryMD, Paul Saladino (CarnivoreMD).
It's easy to stumble upon conflicting information when it comes to nutrition, but I find that just being exposed to more options (rather than eating what everyone eats by default) can give you an opportunity to make the decisions that make sense to you.
That doesn't disprove that depression caused the microbial imbalance in the first place.
It's very reasonable to think that a lot of these systems are bidirectional, and for any individual, you may not know which part of the body was dysfunctional first.
I think we're actually heading into a ditch there. As if you can heal a depression by just changing serotonin levels or improving the gut health. I would say most often there are good reasons the brain put one into "stop what you're doing right now" mode aka depression. Year long experiences, maybe even the most defining years as children.
But I would argue that it might help us move away from SSRIs and stuff. Soften the disease so that it becomes bearable and healable by therapie.
I agree that depression is likely so prevalent because it's adaptive in some cases that are increasingly common now.
I would suggest that rather than look at childhood experiences exclusively, we can look at current circumstances. It's much, much easier to be depressed when you're poor and have no hope for a better life, for example.
You're right, that was my bias! In therapy at least you also look at the current circumstances as you're patterns of behaviour that one learned in the past hold true today as well.
I would be very surprised if body/emotion metaphors weren't endemic in language.
I don't speak too many languages, but I 've noticed that grokking English expressions isn't too hard for most tourists. "Chip on the shoulder", head in the game (or the clouds), foot in the mouth, butterflies in the stomach, etc; all seem fairly understandable to tourists who hear the expression.
Some have a very literal origin - "scared shitless", for example - that I would look for first.
Will be interested to at some point see what kind of connection gastrointestinal autoimmune (among others) diseases such as Crohn’s and Ulcerative Colitis have on not only the guy microbe balance, but mental health as well. Many mental health disorders have strong genetic ties, as well as autoimmune diseases. Wonder if existence of one makes the likelihood of existence of the other greater.
There's some progress now in tying specific mental disorders to autoimmune problems in the brain. Wish I could tell you more but all I know about this is that they test people's cerebral spinal fluid for antibodies against specific neurotransmitter receptors, and they've discovered several connections between those and problems people have.
Very interesting! I actually have both Crohn’s and bipolar disorder, and one anecdote that’s interesting (to me) is that the TNF inhibitor I’m on, which has put Crohn’s in remission, has simultaneously appeared to have a positive effect on the mood disorder side of things as well.
Really cool to see the GI getting so much research!
Edit: Found an interesting study that addresses the relationship between TNF and mood disorders - go figure!
Perhaps Westerners view all non-western science as pseudoscience or made up, but it is a well-known fact in many Eastern cultures (and their medicinal practices) that the stomach is a primary source of disease (and not just depression, but all kinds) when abused through bad eating habits.
Then the wheel is re-invented with intermittent fasting, a diet with less processed foods, more veg/fruit, less meat, etc.
Whenever I see articles about health on HN, I no longer take them too seriously because the reductionist approach to medicine is why people get mistreated for symptoms instead of the disease.
Even the ancient Greeks (the so-called birthplace of "western knowledge") took a more holistic approach than what the sketchy for-profit medical/pharmaceutical cabal does.
But of course, we need to take it seriously because "the scientists say so", even though their own research system is so badly broken that a for-profit cabal runs the publishing arm of research.
"Western Science"'s insistence on procedure, double-blind studies with control groups, finding provable reasons why, etc. have debunked most of pre-modern medicine. That some elements have withstood the test of close examination is not a criticism of our methods, more a validation. As are stunning improvements in life.
No, western science hasn't "debunked" anything with studies. They started out without accepting anything from other cultures, simply because they are from other cultures. As time has passed, the cultural medicines from various cultures have been studied poorly and patented and sold to people, mostly as long-term treatments of symptoms, never as cures. In every country, multinatinational drug cartel has made it impossible for local doctors to evem exist let alone prescribe traditional medicine, unless approved by the cartel, patented by them and sold for a huge margin.
I believe the western medicine overall has created more health problems than it has solved, if you exclude treatment of acute trauma.
I'm sure every culture, including Western ones, has some kind(s) of food everywhere along the "healthy" to "medicinal" scale.
Everyone agrees what you eat is important, nobody can agree on what that should be, hopefully this kind of research will tell us.
> ... When it came to depression, two bacteria [...], Morganella and Kiebdiella, seemed to play a causal role, [...] Morganella has already been implicated in depression. As far back as 2008 ...
This situation looks relatively simple to me - start searching for bactiophages which are specific to Morganella. Briefly test those in animals, then try them on a few volunteers who both are suffering from profound depression and seem to have very high Morganella levels in their guts. (While giving 'em fecal transplants from depression-free relatives and monitoring them intensively and such.)
If that shows promise, then you might really have something (minus a whole lot more testing & refinement & such). If not...maybe back to the drawing board.
Since diet can affect the microbiome of the gut and I can't imagine how gut bacteria affect moods (although I'm open to the idea I suppose) I'd wager it is actually diet and nutritional input that affects mood as well as the gut bacteria. Makes more sense to me that your mood can be affected by your diet, and what we are measuring is the altered microbiome of the gut because of the diet.
> Two patients and no control group is virtually useless for drawing any conclusions
That is a frequentist argument.
If the response to treatment is significant enough, then that is a worthwhile signal (cliché: parachutes save lives without a control group).
Placebo is an obvious contender. However presuming the patients had a chronic condition with plenty of previous interventions, then the placebo effect has had plenty of chances in the past. If it were due to placebo then there would be something to learn about why the placebo effect were so effective in that situation!
..." I can't imagine how gut bacteria affect moods"...
But you can imagine looking at a picture and feeling hungry.
In addition to our fast new electrical nervous system for rapid response
there is the older slower endocrine system from when we were just bags of chemicals coordinating with concentration gradients (still are, but were).
visual -> brain -> signals gut -> gut makes molecules to get ready -> molecules detected report to brain -> you drool
Moods depend on the chemical balance of small molecules
bacteria eat sleep and poop small small molecules.
To consider that after billions of years of coexisting we, both multi cell & single cell, have not adapted to responding each others's small molecules is unthinkable
As mentioned in the article, there is already a causal hypotheses for why the biome itself is the cause, certain people have strong immune responses to the products of these bacteria which causes a chronic inflammatory response.
If you believe that nutritional input has an effect on mood, then, by proxy, you also believe that the microbiome has an effect. We have outsourced a lot of food preprocessing to gut microbes, and if they are wiped out, then you‘ll suffer from malnutrition.
If you ever have/get anxiety/panic attacks you will KNOW where it all starts.. in the stomach. This is not something people imagine. I 100% do not wish this stuff on our worst enemies.
To be fair, I think the parent is that they expect that both are affected in similar ways. That is, gut biome is an effect, not an affect with regard to mood.
The sibling point that treatments targeting the biome would be expected to fail, if that were the case, is complication.
If you’re like me and somehow missed out that there’s an significant mesh of neurons in your guts that’s capable of independent neurotransmitter release, you should look up the enteric nervous system.
Intuitively, at least, it seems to make sense of all the ‘gut’ connections to mood.
It's been described as a "cat's brain" equivalent of neurons. Largely seems attached to regulating various rhythms of the gut, but who knows what computations it could be influencing.
Someone been telling me, my depression comes from bacteria, I KNOW! Pain is... if I eat something plant based, depression and suicidal thoughts come back. Takes about 4 days after I ate the offending food, stays for 3 days, then I'm back to normal and energetic.
Latest experiment was one teaspoon of fermented green squash daily, seemed to work out okay for 5 days or so, then depression came back, BUT I could smell it in my armpits 1-2 days before the thoughts were back.
https://gutsense.org has a lot about fiber - the only fiber I can use seems to be animal based, like eggwhites
Not a doctor but I'd recommend you look into the carnivore diet. See if that helps with your mental health. Keto is a less hardcore version of the diet that might also help.
like amonia or something, sour, no ammount of deodorant can mask it, and the smell can't be removed from clothes. When u wash the clothes you can smell it right when it leaves the washing mashine, it dissappears when it dries but the moment it gets a little moist, like water or sweat the smell is back.
I've tried baking soda, different brands of washing detergent, strong vinegar (25%) to no avail.
The smell goes away about 3 days after I go back to a diet of meat and animal fat. Comes back a bit when I drink strong coffee, so I think it's something like a stress hormone. Energy seems more stable without coffee, but coffee doesn't seem to make me depressed (as much as plant based food does).
I've started suffering from that when puberty hit, but I think depression started earlier (i can remember that colors seemed to have vanished from the world one day)
Wow thank you. Describing 90% of what's similar for me. Surprised to see the ammonia smell, cause I've had the smell for about 6 months now. I'm not overweight, no diabetes, generally healthy. I do drink caffeine and consider it my problem substance.
good luck! Struggelign with caffeine addiction as well, i manage one-two weeks at a time, decaf is a bit easier than switching to black tea - but the tea is def. better for my nerves
Not overweight, average BMI for my body shape/age/gender. I recently went down the diabetes rabbit hole but not of the symptoms are really present. Interestingly enough, when I sensed changes in smell I immediately thought "diabetes" too.
When you've got chronic problems with your gut, it is so frustrating and difficult to try and figure out what's going on. That process alone is enough to make you feel anxious and depressed. In my own experience, I'm not sure whether I have stomach problems because I am anxious, or vice versa. I do know that symptoms of both cropped up at the same time, so in my opinion they are definitely correlated.
It's exciting to see even small breakthroughs in the research that's being done. My heart goes out to those people who are struggling with depression, anxiety, and stomach issues.
I tell my cranky kids this all the time. Or, hopefully, before they get cranky, my kids don't like eating at appropriate times, it's like they're missing the hunger gene or something.
With regards to my kids I usually think "normalize over a week". Most kids that aren't picky eaters will eat more or less on different days. I just try to make sure to have reasonably healthy choices available the days they do eat.
Two days ago my son ate almost nothing for dinner. The day after he ate 6 big broccoli stems, 100g bulgur and one whole can of large white beans. I couldn't believe my eyes.
For those curious, morganella is the main culprit listed here, it seems. Wikipedia isn't clear to me on how one gets this in your biome. Outside of other susp conditions. :(
My personal, completely unsubstantiated take is: your diet allows certain bacteria to thrive (or not). It’s less about trying to avoid the bad ones and more about trying to nurture the good ones. One incredible thing you can do for your gut is eat more fiber; which the vast majority of Americans don’t. Try psyllium husk powder (the stuff in Metamucil). Eat less refined sugar and saturated fat; eat more raw and fermented vegetables. Probiotics are kind of a scam, and are usually really expensive. Like most things with health, you have to consistently do the not-so-fun things to get good results, you can’t just take a pill and move on.
That is as may be, however, this study shows that removing that bacteria helps with mood disorder. And, there is no evidence that diet gives you this bacteria. Nor that it can help remove this one, either.
That is, discussion of diet is a bit of a non sequitur. Not wrong, but also not necessarily relevant.
The paper is titled “ Combined effects of host genetics *and diet* on human gut microbiota and incident disease…” (emphasis mine). Dairy (and the way some people process it, because of genetics) was shown to influence levels of certain bacteria.
The study also does not show that removing Morganella resolved depression; the study did not attempt to remove it, and a researcher is quoted as saying it’s not clear how one would do so (last line of the article):
> But it’s less clear how Morganella could be eliminated from the gut to relieve symptoms. “That’s a bit more challenging.”
Ah, fair. I was going with what I saw as an implication that removing it would help. My apologies.
Clearly, I had not made it through the article to the underlying studies. My reading was that they were looking for lactose related bacteria, but landed on this other one. And that they did not find a way to control it's presence.
I think there is also correlation to the how well people digest food, which coincidentally means that chronic constipation often accompanies depression.
Playing devil's advocate, do we have any reason to believe that people who are genetically more succeptible to depression aren't also more likely to have this sort of gut via genetics? That would result in this correlation.
Perhaps improving your gut biome wouldn't actually help with depression?
If people with depression have this sort of gut, that still doesn’t establish directional cause or mechanism.
The semi-autonomous nervous system in our guts, the microbes in our guts, and our central nervous system have complex chemical signaling interactions. Neurotransmitters linked to effects on mood are generated by the gut.
Therefore, the brain can signal to the gut that it should release neurotransmitters, and the gut can release those neurotransmitters itself.
Because of this interaction, it’s possible the ‘culprit’ for depression is behavior by the brain, microbes on the gut, the gut itself, or the brain-gut interaction (Or any combination of the four.)
or depression causes this bacteria to proliferate more easily?
I see nothing in that research showing causation. It doesn't invalidate their correlation though.
"One of them, Morganella, was significantly increased in a microbial survey of the 181 people in the study who _later_ developed depression."
they would have been diagnosed with depression first leading to increase in morganella, if it was the other way around? agree this could be correlation, but I guess thats why they say that the field is still in its infancy.
That's my thinking as well. Depression leads to lifestyle changes which includes dietary changes which can cause certain bacteria to grow faster, as your gut bacterial makeup changes constantly based on what kind of food you consume and which microorganisms are specialized for it.
I think there will be some breakthroughs by studying the human microbiome, for example there could be reasons that a moderately harmful microorganism or strain becomes dominant in your gut for whatever reason and causes problems, but from my personal anecdotal experience with gut health and diet, I believe most issues will still be solved with dietary changes and perhaps some targeted antibiotics or antimicrobial treatments in general.
I'm also willing to bet we'll discover a lot of immune involvement in the regulation of various bacterial population in the gut. There must be an adaptive system that minimizes or eliminates most harmful organisms in the gut, otherwise we'd all be dead.
> Morganella has already been implicated in depression. As far back as 2008, researchers investigating a possible link between depression and inflammation found depressed people had stronger immune responses to chemicals produced by Morganella and other gram-negative bacteria in the gut. Thus, the newest study seems to be “further proof” that inflammation caused by gut microbes can influence mood, Gilbert says.
> Thus, the newest study seems to be “further proof” that inflammation caused by gut microbes can influence mood
Of course it bloody can - if you have IBS or any number of other gut-related problems, believe me you are very likely to be depressed, because the symptoms of these are very nasty and humiliating. This does not mean that the bacteria are directly affecting the CNS.
It seems pretty obvious from reading the article in its entirety that the claim is that the inflammation is affecting mood directly, not via nasty and humiliating gastro symptoms.
The same way you support any causal claim, by controlling for confounders. What gives you so much confidence that a suboptimal microbiome is tautologically accompanied by "nasty and humiliating" IBS symptoms, to the degree that would cause depression? Are you under the impression that everyone with a measurably poor microbiome automatically has nasty and humiliating IBS symptoms?
You can assume that everyone involved in performing, analyzing, and reporting the study is incompetent, but at that point why not just assume that the entire article is inaccurate and that one can never understand anything about the world?
I'm the last person to slavishly believe scientific authorities' interpretation of evidence when it's clearly done poorly (see: all of Covid). But it's bizarre to claim that researchers wouldn't have thought to rule out the most basic alternate hypotheses, especially when they have the data to do so.
Tangential: Is there any evidence that pro biotic foods or supplements can increase gut health? Given the evident importance of gut health, I wonder whether it's worth using something like this, to grab a random example: https://www.amazon.co.uk/Restored-Bio-Cultures/dp/B082SZXBF2...
I used be lethargic, couldn't get myself to do anything but be on the sofa. I would get horrible migraine headaches if drinking alcohol or even alcohol free beer or eat certain foods. I self-diagnosed histamine intolerance through trial and error.
I tried multiple pro-biotic combinations. An easy one I tried in the beginning was simply some Danone Actimel the family had in the fridge anyway. I can attest to the fact that it contains live bacteria (a strain that makes lots of histamines) that do make it to the gut because it gave me the horrible migraine headache as would Sauerkraut actually. Researched what strains don't create lots of histamine. I landed on Garden of Life - Primal Defense Ultra. What I think made the difference is that it contains Bacillus subtilis. I say that because I tried two or three others that had largely the same makeup of strains but none had that particular bacterium. It's a soil based bacterium which you might get from eating your own cabbage you grew in the garden as well. Almost everything else just has various different strains of lactobacilli.
Taking 3 capsules a day I felt like crap for 2 weeks (no headaches, just feeling sick, like a bad cold) and then things got better. I am able to drink alcohol again (I'll get a hangover headache like anyone would if I drink too much but it's not longer a day long migraine from just sipping 10ml) and eat anything I want to in any quantity. I still take one in the morning and one in the evening and I put one into the Sauerkraut I make.
YMMV as always, not a doctor, try at your own risk, not affiliated etc :)
Thanks for sharing this, most of your experience sounds similar to those of a friend of mine (Yokult gives them migraines) although they haven't yet tried Bacillus subtillis.
Probiotic and gut biome research is all over the place.
It’s possible to find some studies showing correlations, but it’s harder to find successful replications of those studies.
Some probiotics have been shown to temporarily alter gut flora, but it usually reverts after the probiotic is stopped. Dietary and activity changes are generally good at improving the biome.
It doesn’t help that one of the commercial guy biome measuring companies basically turned out to be fraudulent a few years ago. Even some of the public efforts to measure correlations are suspect or bunk because they relied on these services.
As a fellow comment says - its all over the place and kind of hard to say, see [1] saying they are useless but lots of studies saying they are useful .
Personally as someone with IBS, I have tried many probiotics over the years and have mixed results - most of them were useless but for some time I found one or 2 that worked but I couldnt say for sure if they worked due to other factors (for e.g generally healthier food, lifestyle, mindset etc). You would have to try it out for weeks to see their effect (according to studies that say it work).
The doctors I spoke to though gave me strong probiotics (>100 billion CFU, for e.g something like [2]). I found anything that had 1 or 10 billion CFU to be pretty much useless.
I think you should work on your diet before taking probiotics. I dont think I am lactose intolerant, milk gives me bad bloating but yogurt doesnt. Yogurt worked for me over the course of weeks, kefir and sauerkrat gave me mega-bloating.
Not sure if you have heard of the low FODMAP diet? Its now the standard treatment for IBS. The theory is certain bacteria ferment FODMAPS into gas and water which leads to the symptoms. They don't know which bacteria yet but going low fodmap is now a well researched and accepted treatment.
Everyone is different but personally, I'm able to tolerate everything except Fructans (one of several types of FODMAPS). So no garlic, onion or wheat for me.
Yes of course. I did low-fodmap for many months few years ago and continue to do it (when I go to an unknown place for example or travel).
In studies Low-fodmap is typically only recommended for ~6 weeks. I now try to eat any kind food though, I eat everything in smaller quantities and this also helps.
I personally found that a combination of diet, stress, sleep control are the most effective for managing IBS symptoms. Any one of those can flare up the symptoms at any time and managing all of them is key
I was skeptical of this when I first heard of it several years ago. It sounded just like every other popular diet does: “Just (don’t) eat this certain food, and you will feel amazing!”
But I have several family members on it right now, and they all report feeling WAY better. And this is after years of dealing with IBS type problems too.
Low FODMAP works, but it’s precisely because it’s unlike all other “diets”. It’s a systematic removal of basically all short-chain sugars. The problem with it, as someone who was instructed to follow it, is that it’s extremely unintuitive to know what foods are low or high FODMAP without the list. Because of this, it’s really easy to make mistakes unless you consult the list prior to eating.
So it definitely gives positive results, but it’s also very difficult to follow.
As someone on FODMAP, what works for me is to do breakfast/lunch meal replacement with low FODMAP shakes (like Huel), then get a few FODMAP cookbooks and make dinners out of that. Works great and is fairly painless - lots of delicious meals can be made that are low fodmap, fortunately. It's really difficult to avoid FODMAPs when eating out, western food loves onions and garlic for instance - for these cases, I use alpha-glucosidase enzyme tablets (I take 2x 350mg tablets with a meal).
Eat fiber. Meet the recommended amount and eat a diverse set of fiber which will feed different microbes in the gut. It will take some time for the gut to adjust to the new levels though. Expect gas, cramping, etc for a few days.
Do you advise just fiber from natural foods, or do you take a fiber supplement (like those that come in powder form)? I guess the supplement route won't give me the diverse fiber types you mention, am I right?
The best treatment for my own ADHD, depression and anxiety is living a healthy lifestyle, across the board, full stop.
It means regular exercise, 6 hours of cardio a week, eating healthy, meditating, spending time in the sun, etc. etc. (And anti-depressants/therapy, which play an important role too.)
Of course, it's too much to tell someone struggling to do all those things, but if you can work towards that, I strongly recommend it. I've had to declare war on my depression and ADHD because I can't afford to have it in my life anymore.
At some point perhaps the science will catch up and explain precisely how these things help, but until then, I feel like you have to take the ancient approach of observing people who have things figured out and emulating them. (And I say this as someone who is very much pro-science.)
What was your diet like when you were taking them? It's been observed in some studies that delivered mixed results that responders had better diets (i.e. more bacteria friendly components in the diet such as indigestible carbs from vegetables/legumes/fruit etc) whereas non-responders had weaker diets in terms of providing the gut microbes nutrients.
Diet is now generally low-FODMAP, emphasis on reducing fructose, glucose, and sugar alcohols e.g. sorbitol, erythritol, to which I seem especially sensitive -- this may be atypical among IBS patients.
I've come across plenty of evidence in the literature but there are lot of variables that can prevent any positive effects from taking place. If you're taking probiotic supplements in isolation and the rest of your diet is suboptimal in terms of bacteria-friendly nutrients, it's unlikely that you'll get results. It could be the case that many people are throwing money away if they're taking probiotic supplements without addressing their diet and lifestyle.
There's so much variety between people, one formulation for one person might work well for one person but have negative effects on another even if they have a supportive diet and lifestyle. People might simply have to trial multiple formulas that have the right mix of strains before they find one that works for them.
Prebiotic foods seem to have more consistent results on gut health, according to some studies.
Personally kefir, sauerkraut, kimchi, kombucha - all give me lots of bloating even after trying out for weeks. Maybe thats just how its supposed to be? Not sure but I stopped after a while after it affected my daily life
I have some odd GI issues so there's a clear impact there. The alternative treatment is some very nasty medication. Effective probiotics restore normality without the side effects the medications have. I'll spare you the details ;)
More anecdotally I do feel generally better even when my GI symptoms aren't present: more energy, better mood, more restful sleep.
I use a variant of Emmymade's variant of Maangchi's recipe. It works really well.
Rinsed pickle jars work great, a head of Napa cabbage usually fills about 2+1/2 ~ 3 jars. If you're not into high spicy, dial back the red pepper by about half, for your first try. If you don't like funky, skip the fish sauce or any seafood component, I always do this so that the flavor won't clash with some dishes, you can always add fish sauce to a dish but you can't remove it.
I ferment it for about 3 days at about 65 ~ 68 degrees(f), then into the fridge. It keeps indefinitely but is best within a few months.
Do not bring it into work, just as you would not microwave fish at work. The aroma is very much not to everyone's preference, even when made without seafood.
it would never have occured to me not to bring kimchi to work. Durian? Stinky Tofu? ok but Kimchee? I'll bet most company cafeterias have blue cheese around
Not GP and don't have one to suggest, but as you're asking for 'easy' (and at risk of stating the obvious, but only once you know I suppose) - ignore anything that says something like 'refigerate for 30mins and enjoy'.
Or don't, I'm not denying quick such er salads can taste great, just that if what you want is a fermented or pickled product, that takes time. (And much longer if at all in the fridge - that's their purpose!)
A 'proper' recipe for sauerkraut for example will tell you something on the order of weeks at minimum, and it's done when you like the taste. Kimchi I think is typically fermented for longer, more like months or over a year (not including any transferred to the next batch).
Most lactofermented foods are: Main ingredient, spices, a few tbsp of salt. Add to sterile jar, fill with water (add a glass weight to the top if needed to keep everything submerged) and leave in a dark cabinet for a few weeks. Trial and error to get the flavor the way you want it, but that's basically it. If you see little air bubbles forming near the bottom after 2-4 days, you have a live culture.
Rather than using these processed foods, one should provide the gut microbiome with “food” in the form of fiber from whole plant foods, i.e. not ‘fiber’ supplements like Metamucil.
Micro biome is a literal pile of shit. Please forgive me because I couldn’t resist, but I think it’s massively overhyped and useless. It’s obviously going to be correlated to lots of things. But people measure the rough correlation and take it way too far. There’s nothing there… and if there is then it’s downstream of something more fundamental. Inflammation/metabolomics is the real revolution.
> Together, these data have important implications. We show that dietary fiber and probiotic use, factors known to affect the gut microbiome, are associated with differential outcomes to ICB. Although causality cannot be addressed from the observational human cohort, where unmeasured confounders may exist, our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics—with suppression of intratumoral IFN-γ T cell responses in both cases.
It would be a bit disappointing if the final conclusion from all this microbiome work was 'Eat more vegetables'...
[1] https://www.science.org/doi/10.1126/science.aaz7015