3 ms·

Microbiome researcher here. We routinely use germfree mice, rats, and pigs in our research. They are completely devoid of bacterial and fungal cells. Their imm

by wdwvt1 7y ago

Microbiome researcher here. 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.

aldoushuxley001 7y ago
Interesting. 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.
- wdwvt1 7y ago
  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
  - 18pfsmt 7y ago
    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.
  - aldoushuxley001 7y ago
    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.
zxcb1 7y ago
To me it sounds as if the proper metaphor is ecology. If you turn a rainforest into a desert, does it change the climate for the rest of the planet?
tacon 7y ago
>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. Pulp Fiction: The Truth about Fiber http://www.diagnosisdiet.com/food/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/ 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 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.
- pazimzadeh 7y ago
  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 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 https://sci-hub.tw/10.1038/s41579-019-0213-6 [Box 3]).

by wdwvt1 7y ago

aldoushuxley001 7y ago

Interesting. 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.

wdwvt1 7y ago
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
- 18pfsmt 7y ago
  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.
- aldoushuxley001 7y ago
  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.

zxcb1 7y ago

To me it sounds as if the proper metaphor is ecology. If you turn a rainforest into a desert, does it change the climate for the rest of the planet?

tacon 7y ago

>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. Pulp Fiction: The Truth about Fiber http://www.diagnosisdiet.com/food/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/ 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 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.

pazimzadeh 7y ago
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 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 https://sci-hub.tw/10.1038/s41579-019-0213-6 [Box 3]).