> humans and microbiota: each needs the other to survive
Would we literally die without the microbiome? At least with respect to gut flora, the answer is no[1]. I'd be interested to hear about some part of the microbiome that is absolutely essential to human development or human survival, the way skin and blood are essential. As far I've been able to determine, a human being could live 5 years on Mars with a stockpile of processed food[2], water, and oxygen, and without the microbiome or any organism within a hundred million kilometers. It would be very interesting if that's proven wrong.
I don’t think your first citation actually proves humans can live without gut microbiota. I simply don’t see evidence that’s the case and it would be very very difficult to demonstrate.
In most cases humans with severely disrupted gut microbiota (diminished populations) end up in severe pain and health complications.
I sincerely doubt a human could live on mars without a gut microbiota (or anywhere for that matter); we’re actually not just simple systems that require only basic inputs to function.
We routinely use germfree mice, rats, and pigs in our research. They are completely devoid of bacterial and fungal cells. Their immune systems develop abnormally and they have some behavioral oddities, but they have no reduction in lifespan or fecundity.
Nutrient capture is really not that large a part of the gut microbiomes role; most of the nutrient and caloric uptake occurs in the small intestine of humans. The small intestine has many bacteria, but maybe 1e-3 fraction of the large intestine. Interestingly, humans have a much larger small intestine:large intestine ratio than close primates. Likely we evolved on such a high quality diet (animal protein) that our need to extract nutrients from plants declined and allowed shortening of the large intestine. When you get high quality feed, you don't need a big bioreactor to ferment plants into calorically valuable products like short-chain fatty acids.
This is not to say that humans aren't better off eating a very plant rich diet. All the research suggests strongly that a diet very high in fiber feeds a healthy guy microbiome which helps resist pathogen invasion and helps create a balanced immune system.
In short: if you could rear germ free humans, I think they'd be just fine, if perhaps immunologically odd.
I'm curious though, considering bacteria, fungal spores and viruses are always floating in the air around us to some extent, and almost all food similarily has bacteria, fungi and viruses in it (to some extent), how do you keep germfree mice, rats and pigs germfree? What are you feeding them? And what about them just being exposed to normal air?
I can't help but think of a GI tract completely devoid of bacterial and fungal cells as being a massive power vacuum essentially. And even if germfree mice, rate and pigs are born that way, wouldn't it be incredibly difficult to prevent these free-floating bacteria or fungal spores from inoculating their GI tracts? whether just through air or food?
I would love to see a study analyzing a germfree mouse, rat or pig that was kept germfree to full life as best as possible and then do an analysis on their microbiome to see if, in fact, they are germfree at the end of their life too. I'm not confident they would be.
They are kept in vinyl bubbles. The only things that enter the bubbles go through sterilization: a liquid sterilization for tubes/plasticware, etc., irradiation for food, autoclave sterilization for water and liquids. Germfree animals have been around for more than 70 years - they are actually not that hard to create in rats and mice because a fetus is sterile in utero.
> I can't help but think of a GI tract completely devoid of bacterial and fungal cells as being a massive power vacuum essentially
This is absolutely true for the right organisms. Surprisingly there are quite a few common human gut microbes that cannot colonize a germfree gut. Reasons are still not totally understood.
> I would love to see a study analyzing a germfree mouse, rat or pig that was kept germfree to full life as best as possible and then do an analysis on their microbiome to see if, in fact, they are germfree at the end of their life too. I'm not confident they would be.
This paper [0] from 1971 is a good review of the 40's and 50's work showing that germfree hosts are basically normal and can be easily maintained as sterile with proper procedure.
[0] Gordon and Pesti, The Gnotobiotic Animal as a Tool in the Study of Host Microbial Relationships, Bacteriological Reviews, 1971
This idea that you can find any multicellular organism without any dependency on another organism is without merit. One cannot achieve a "pure system." At the very least, evolution depends on variation within the genetics.
Fascinating, thanks for the reply. I always love hearing the protocols for requirements like this, makes a lot of sense tho, re: the sterilization techniques (irradiation for food, autoclave for liquids, etc.).
I'm surprised the germ-free animal models had such surprisingly normal lifespans. Thanks for the link too.
Part of me is still skeptical of the degree to which the germfree animal models are in fact germ free at the end of their lives (I'll have to do some more digging through the literature).
Seems like these germfree animal models should yield some great insights into the microbiome tho.
Just curious, what sort of projects are you working on? It's a fascinating field.
Slash, what are your opinions of all these microbiome mapping tests (e.g. Viome, etc.). I mean, our microbiomes seem to change fairly frequently such that a singular snapshot at these relatively infrequent intervals seems inadequate for most uses.
>All the research suggests strongly that a diet very high in fiber feeds a healthy guy microbiome which helps resist pathogen invasion and helps create a balanced immune system.
References please. There is plenty of research that suggests no such benefit of very high fiber, and plenty of issues.
These are not great sources. Your first link is mostly anecdotes and doesn't differentiate between "necessary" and "sufficient". No one is claiming that fiber alone will solve all of your health problems. There are also many types of fiber, even within the 'soluble' and 'insoluble' categories, with different properties.
You likely have a point since anything in excess can be harmful, but those references don't really support.
One thing to keep in mind is that you shouldn't switch diets drastically - you can't expect your low fiber/high sugar microbiota to be able to handle a large dose of fiber all at once. Think of your microbiota as something you need to cultivate.
By the way, there's increasing evidence that in the absence of fiber your gut bacteria resort to chewing back your own mucus, whereas if you give them some complex fiber to chew on they leave you alone (https://sci-hub.tw/10.1080/19490976.2018.1513765). This is temporary however and in the absence of fiber you can maintain barrier function if you simply make more mucus. But that requires more energy so you probably have to eat more. Everything has tradeoffs.
And other that just giving you the farts, many byproducts of fermentation like short-chain fatty acids (i.e. butyrate, propionate), are able to keep other bacteria at bay while simultaneously feeding your colon cells and keeping them in a non-inflamed state (https://sci-hub.tw/10.1038/s41579-019-0213-6 [Box 3]).
Actually living on Mars might be one of the only ways to successfully live without any microbes, because a huge part of the gut microbiota is needed to train your immune responses to other microbes. But if there are no other microbes around you'd be ok for a while, but would probably develop autoimmunity or have other immune problems eventually.
This doesn't kill all bacteria. C. diff. infections sometimes happen during a course of antibiotics because that species isn't killed by the treatment, while bacteria that would keep C. diff. populations in check are killed.
>> As far I've been able to determine, a human being could live 5 years on Mars with a stockpile of processed food[2], water, and oxygen, and without the microbiome or any organism within a hundred million kilometers. It would be very interesting if that's proven wrong.
If one started with a healthy biome and ate processed foods you would feed the existing biome and you could survive. How many people are living off of processed foods now?
If you somehow killed the existing biome it would grow back quickly.
I have been away from it for a while and am sure they are improving but witnessed Herculean efforts to get zebra fish to survive in a zero bacteria environment.
Not an expert so you can disregard every word I say.
Answer to your question depends on functions provided by gut microbes. We can say it's to digest the food and it's symbiotic relationship. But what if this is what we know only on the surface. What if these microbes produce proteins that are absolutely essential for many other functions as well. What if they signal messages that are of neural nature.
It's a pitfall to think that our brain is all we are as it hosts consciousness. I held this view for a long time, so I understand where it's coming from.
But try changing your diet. I won't make any suggestions but there are limitless option to biohack your body. You will see amazing effects on your brain too.
Btw, there's a neural setup i.e a brain in stomach and heart as well.
This is actually something we are able to measure. I don't find fault with anything else you claimed, but what are your credentials with regard to this topic? I'm not trying to gate-keep, but my undergrad was biochem and there are many well-understood fundamentals that some folks are not willing to concede, or that their 'theories' disregard.
I am happy to learn more on this (see my first sentence). But to keep this on focus and constructive. Your diet absolutely influences the protein absorption. Human body does not produce all the proteins that it needs. Need to come from the food. Change food, change bacteria. Change your body's capability to digest/absorb those proteins.
> But try changing your diet. I won't make any suggestions but there are limitless option to biohack your body. You will see amazing effects on your brain too.
I won't as these things are so experimental. But I will give you an assertion that body and mind influences each other. More so from the body's side than from the mind's
If one were to look at human biochemistry over time, modern tech has increased average life-spans, but we've done so at the expense of quality of life. Take the 'ultra-pasteuraization' process of milks as an example, it's massively reduced gut flora variety.
They are selling expensive pills with probiotic entities that should be "free" with food we consumed for centuries. We went overboard on the sterilization. I just bought into a cattle herd so I could buy raw milk (which Europeans never lost access to, so we can compare notes).
The microbiome manifests itself whether one is on Earth or not, and whether one wants it to or not. Its composition, however, will vary based on the food consumed. Microorganisms are quite prevalent in the atmosphere whether they are wanted or not; that's how me making my own sauer kraut is possible.
Each of your cells uses hundreds of mitochondria to generate energy, so we have effectively tamed a part of our ancient microbiome into directly working for us.
A similar type of taming seems to be occurring at intestinal surfaces covered in mucus, where the body secretes a complex mixture of protein and sugars that simultaneously keeps the bulk of microbes at bay while actually feeding desirable bacteria.
You wouldn't die of lack of microbiome, you'd die of being unable to maintain your sterile environment and eventually being infected, unless you lived in a bubble (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477854/), and Mars is actually not too far from that. Much better to allow yourself to be colonized by harmless bacteria which will fill up all the ecological niches that the pathogens require to thrive.
>Perhaps the most popular is the gut microbiome, which impacts human digestive health (this is the science behind your daily probiotic yogurt).
I don't believe there is any science behind the notion that yogurt is healthy for your gut as a probioitic. The bacteria in yogurt is lactobacillus, which is present in gut flora but a minor resident at best.
https://en.m.wikipedia.org/wiki/Gut_flora
>About 99% of the large intestine and feces flora are made up of obligate anaerobes such as Bacteroides and Bifidobacterium.
These are not present in yogurt and no amount of yogurt eating will help introduce them to your gut.
The selective constraint on gut bacteria is not merely to eat food, it is to facilitate the health of the gut. That is, a symbiote has different evolutionary goals than a bug that is just out for a meal. Don't go looking in rotten food for this stuff; the most likely place to find it is in another person's gut.
The theory is it's a symbiotic relationship. Very, very few probiotic strains are actually capable of colonizing your gut, rather their presence is beneficial for the bacteria you already have.
Description
The human microbiota is the aggregate of microorganisms that resides on or within any of a number of human tissues and biofluids, including the skin, mammary glands, placenta, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, biliary and gastrointestinal tracts.
Hippocrates is said to have claimed that "all disease starts in the gut". There's been some very interesting research coming out the last few years that seem to tie autoimmune diseases such as psoriasis [1] [2] to the gut.
It's been known for a while that some gut disorders, including Crohn's, can manifest as skin lesions of various kinds, and bowel bypass patients can also develop skin symptoms. It's also known for a while that autoimmune patients have less bacterial diversity in their gut, and an increased abundance of certain types of bacteria, especially in the small intestine. Research has found that in such patients, gut bacteria can migrate from the gut to the bloodstream and then to the skin. Psoriasis patients, for example, have a much higher gut permeability than non-psoriatics (not to be confused with the pseudoscientific Internet hysteria around "leaky gut"!) and have deficient bile acids.
Treatment would involve resetting the gut somewhat by eradicating the known pathogens. Astonishingly, a Hungarian study in 2003 [3], which used an experimental treatment with bile acid supplementation, was able to completely clear psoriasis in 78% of its subjects (even more in a second, more acute group), which is unheard of, and about 58% were still clear 2 years later. I don't know why that study hasn't revolutionized things; it's only been cited 11 times according to Scopus.com.
You can reverse intestinal permeability though diet. However, there is no money in it and neither is it a complicated treatment. Thus, the papers about it won't get published in prestigious journals.
Brain Maker: The Power of Gut Microbes to Heal and Protect Your Brain for Life by Perlmutter
I have a theory that fad diets like keto, paleo, primal blueprint, low fodmap, whole 30 (of which there are numerous people claiming they have major improvements) really work because they influence the gut biome.
I cant speak for other diets but I follow low fodmap diet as I suffer from IBS. I always assumed that I was prescribed that diet to influence the gut bacteria. I mean the bacteria ferment on high fodmap foods and bloat and distend your stomach.
Talking about low fodmap specifically I wouldnt call it fad as it has been and is being researched and has shown to be effective to help with IBS, maybe not so much for other conditions.
Personally I have found it helpful in reducing the symptoms that I have.
Keto is working for me to treat AS specifically for this reason. Had to experiment a long time to find the right diet. If I stray I flare up pretty quickly.
I'm curious to know much the journal prestige actually factors in to the odds of the described medical technique eventually becoming a usable clinical practice. I wonder if anyone has done that kind of analysis and published results.
47 comments
[ 2.8 ms ] story [ 97.0 ms ] threadWould we literally die without the microbiome? At least with respect to gut flora, the answer is no[1]. I'd be interested to hear about some part of the microbiome that is absolutely essential to human development or human survival, the way skin and blood are essential. As far I've been able to determine, a human being could live 5 years on Mars with a stockpile of processed food[2], water, and oxygen, and without the microbiome or any organism within a hundred million kilometers. It would be very interesting if that's proven wrong.
[1] http://www.sciencedirect.com/science/article/pii/S0165247805...
[2] I mean non-living food of course.
In most cases humans with severely disrupted gut microbiota (diminished populations) end up in severe pain and health complications.
I sincerely doubt a human could live on mars without a gut microbiota (or anywhere for that matter); we’re actually not just simple systems that require only basic inputs to function.
We routinely use germfree mice, rats, and pigs in our research. They are completely devoid of bacterial and fungal cells. Their immune systems develop abnormally and they have some behavioral oddities, but they have no reduction in lifespan or fecundity.
Nutrient capture is really not that large a part of the gut microbiomes role; most of the nutrient and caloric uptake occurs in the small intestine of humans. The small intestine has many bacteria, but maybe 1e-3 fraction of the large intestine. Interestingly, humans have a much larger small intestine:large intestine ratio than close primates. Likely we evolved on such a high quality diet (animal protein) that our need to extract nutrients from plants declined and allowed shortening of the large intestine. When you get high quality feed, you don't need a big bioreactor to ferment plants into calorically valuable products like short-chain fatty acids.
This is not to say that humans aren't better off eating a very plant rich diet. All the research suggests strongly that a diet very high in fiber feeds a healthy guy microbiome which helps resist pathogen invasion and helps create a balanced immune system.
In short: if you could rear germ free humans, I think they'd be just fine, if perhaps immunologically odd.
I'm curious though, considering bacteria, fungal spores and viruses are always floating in the air around us to some extent, and almost all food similarily has bacteria, fungi and viruses in it (to some extent), how do you keep germfree mice, rats and pigs germfree? What are you feeding them? And what about them just being exposed to normal air?
I can't help but think of a GI tract completely devoid of bacterial and fungal cells as being a massive power vacuum essentially. And even if germfree mice, rate and pigs are born that way, wouldn't it be incredibly difficult to prevent these free-floating bacteria or fungal spores from inoculating their GI tracts? whether just through air or food?
I would love to see a study analyzing a germfree mouse, rat or pig that was kept germfree to full life as best as possible and then do an analysis on their microbiome to see if, in fact, they are germfree at the end of their life too. I'm not confident they would be.
> I can't help but think of a GI tract completely devoid of bacterial and fungal cells as being a massive power vacuum essentially
This is absolutely true for the right organisms. Surprisingly there are quite a few common human gut microbes that cannot colonize a germfree gut. Reasons are still not totally understood.
> I would love to see a study analyzing a germfree mouse, rat or pig that was kept germfree to full life as best as possible and then do an analysis on their microbiome to see if, in fact, they are germfree at the end of their life too. I'm not confident they would be.
This paper [0] from 1971 is a good review of the 40's and 50's work showing that germfree hosts are basically normal and can be easily maintained as sterile with proper procedure.
[0] Gordon and Pesti, The Gnotobiotic Animal as a Tool in the Study of Host Microbial Relationships, Bacteriological Reviews, 1971
I'm surprised the germ-free animal models had such surprisingly normal lifespans. Thanks for the link too.
Part of me is still skeptical of the degree to which the germfree animal models are in fact germ free at the end of their lives (I'll have to do some more digging through the literature).
Seems like these germfree animal models should yield some great insights into the microbiome tho.
Just curious, what sort of projects are you working on? It's a fascinating field.
Slash, what are your opinions of all these microbiome mapping tests (e.g. Viome, etc.). I mean, our microbiomes seem to change fairly frequently such that a singular snapshot at these relatively infrequent intervals seems inadequate for most uses.
References please. There is plenty of research that suggests no such benefit of very high fiber, and plenty of issues.
Pulp Fiction: The Truth about Fiber
http://www.diagnosisdiet.com/food/fiber/
Ditto on the claim about a very plant rich diet being better:
https://www.diagnosisdiet.com/food/vegetables/
Little Shop of Horrors? The Risks and Benefits of Eating Plants — Georgia Ede, M.D.
https://vimeo.com/52606062
One of the key issues is lack of a study that varies only the amount of fiber, and does not substitute fiber for processed carbohydrates.
You likely have a point since anything in excess can be harmful, but those references don't really support.
One thing to keep in mind is that you shouldn't switch diets drastically - you can't expect your low fiber/high sugar microbiota to be able to handle a large dose of fiber all at once. Think of your microbiota as something you need to cultivate.
By the way, there's increasing evidence that in the absence of fiber your gut bacteria resort to chewing back your own mucus, whereas if you give them some complex fiber to chew on they leave you alone (https://sci-hub.tw/10.1080/19490976.2018.1513765). This is temporary however and in the absence of fiber you can maintain barrier function if you simply make more mucus. But that requires more energy so you probably have to eat more. Everything has tradeoffs.
And other that just giving you the farts, many byproducts of fermentation like short-chain fatty acids (i.e. butyrate, propionate), are able to keep other bacteria at bay while simultaneously feeding your colon cells and keeping them in a non-inflamed state (https://sci-hub.tw/10.1038/s41579-019-0213-6 [Box 3]).
People with SCID have to live in a filtered air bubble (https://en.wikipedia.org/wiki/Severe_combined_immunodeficien...) so it's possible, but if I remember correctly there are side effects. Mars is kind of a similar lifeless bubble though.
How did you prove this? How do I prove you wrong?
If you somehow killed the existing biome it would grow back quickly.
this sort of stuff
https://www.sciencedirect.com/science/article/pii/S0091679X1...
Off hand I would expect living without our microbiomes to be similar to slow starvation while gorging on junk food.
Answer to your question depends on functions provided by gut microbes. We can say it's to digest the food and it's symbiotic relationship. But what if this is what we know only on the surface. What if these microbes produce proteins that are absolutely essential for many other functions as well. What if they signal messages that are of neural nature.
It's a pitfall to think that our brain is all we are as it hosts consciousness. I held this view for a long time, so I understand where it's coming from.
But try changing your diet. I won't make any suggestions but there are limitless option to biohack your body. You will see amazing effects on your brain too.
Btw, there's a neural setup i.e a brain in stomach and heart as well.
This is actually something we are able to measure. I don't find fault with anything else you claimed, but what are your credentials with regard to this topic? I'm not trying to gate-keep, but my undergrad was biochem and there are many well-understood fundamentals that some folks are not willing to concede, or that their 'theories' disregard.
Can you give an example?
Xylitol kills some harmful micro organisms like S. Mutans and Candida Albicans.
Xylitol will shift fecal bacteria from gram-negative (covered in a layer of slime) to gram-positive (no slime, healthier).
Xylitol will cause diarrhea but it's a good kind of diarrhea, plan accordingly.
They are selling expensive pills with probiotic entities that should be "free" with food we consumed for centuries. We went overboard on the sterilization. I just bought into a cattle herd so I could buy raw milk (which Europeans never lost access to, so we can compare notes).
The microbiome manifests itself whether one is on Earth or not, and whether one wants it to or not. Its composition, however, will vary based on the food consumed. Microorganisms are quite prevalent in the atmosphere whether they are wanted or not; that's how me making my own sauer kraut is possible.
https://www.cell.com/cell/fulltext/S0092-8674(18)31102-4
A similar type of taming seems to be occurring at intestinal surfaces covered in mucus, where the body secretes a complex mixture of protein and sugars that simultaneously keeps the bulk of microbes at bay while actually feeding desirable bacteria.
You wouldn't die of lack of microbiome, you'd die of being unable to maintain your sterile environment and eventually being infected, unless you lived in a bubble (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477854/), and Mars is actually not too far from that. Much better to allow yourself to be colonized by harmless bacteria which will fill up all the ecological niches that the pathogens require to thrive.
I don't believe there is any science behind the notion that yogurt is healthy for your gut as a probioitic. The bacteria in yogurt is lactobacillus, which is present in gut flora but a minor resident at best.
https://en.m.wikipedia.org/wiki/Gut_flora >About 99% of the large intestine and feces flora are made up of obligate anaerobes such as Bacteroides and Bifidobacterium.
These are not present in yogurt and no amount of yogurt eating will help introduce them to your gut.
It's been known for a while that some gut disorders, including Crohn's, can manifest as skin lesions of various kinds, and bowel bypass patients can also develop skin symptoms. It's also known for a while that autoimmune patients have less bacterial diversity in their gut, and an increased abundance of certain types of bacteria, especially in the small intestine. Research has found that in such patients, gut bacteria can migrate from the gut to the bloodstream and then to the skin. Psoriasis patients, for example, have a much higher gut permeability than non-psoriatics (not to be confused with the pseudoscientific Internet hysteria around "leaky gut"!) and have deficient bile acids.
Treatment would involve resetting the gut somewhat by eradicating the known pathogens. Astonishingly, a Hungarian study in 2003 [3], which used an experimental treatment with bile acid supplementation, was able to completely clear psoriasis in 78% of its subjects (even more in a second, more acute group), which is unheard of, and about 58% were still clear 2 years later. I don't know why that study hasn't revolutionized things; it's only been cited 11 times according to Scopus.com.
[1] https://www.ncbi.nlm.nih.gov/pubmed/29908580
[2] https://www.nature.com/articles/nrmicro2974
[3] https://www.sciencedirect.com/science/article/pii/S092846800...
I have a theory that fad diets like keto, paleo, primal blueprint, low fodmap, whole 30 (of which there are numerous people claiming they have major improvements) really work because they influence the gut biome.
Talking about low fodmap specifically I wouldnt call it fad as it has been and is being researched and has shown to be effective to help with IBS, maybe not so much for other conditions.
Personally I have found it helpful in reducing the symptoms that I have.
:thinking:
I don't know about this guy. I got that link from quackwatch.
https://www.nature.com/articles/s41598-019-42183-0