Gut bacteria... some general questions

[CaptainPanic]

First a quick question: How do gut bacteria end up in your gut? Sounds maybe like a silly question, but I always learned that your stomach (or rather the acid in it) is able to sterilize a lot of food, isn't it? So, how do these bacteria get in your gut? Wikipedia suggests it's (also?) orally.

 

Since up to 60% (wt) of the dry mass of feces (*) can be made up of these gut bacteria, which suggests that they grow rather quickly, and therefore must consume quite a bit of food, what do humans have to gain from it? Wikipedia suggests a whole list of useful functions... but somehow it still seems like the bacteria get the better deal here. It reads like a hijack: without the bacteria, we get sick, develop allergies and possibly even starve. They hold us hostage! So, yeah, they've got some enzymes we don't have. But how difficult can it be to evolve some additional enzymes? The only reason we don't have them, is that we've been hijacked by gut bacteria for so long (since literally forever?) that we never had to evolve them.

 

Somehow, as a chemical engineer, it seems awfully inefficient. You have bacteria to do some work, but then you put them into a plugflow reactor, and you discard the bacteria when they're at the end. It's crap (crappy pun definitely intended). That means you must continuously grow new ones at a high cost. I mean, there's a reason that many processes try to immobilize the microorganisms: that is so you can operate the process with a minimum growth of the microorganisms, and optimize the useful functions of the microorganisms.

 

Has anyone done any research on the energy balance? What percentage of the food we take in is used by the bacteria, and what percentage by "ourselves" (with ourselves defined as that part of our body that has the DNA we call human)? I never really thought of gut bacteria until quite recently... you never realize that I am an ecosystem. But everything I eat is automatically shared. And that ecosystem I carry in me grows a hell of a lot faster than myself.

 

So, the way I see it (and I am not an expert, I'm a chemical engineer, not a biologist!), we're hijacked by bacteria. We can't live without them. And to make matters worse, we work with a suboptimal reactor design that is not capable of immobilizing these bacteria, so we must continuously grow new ones.

 

Is it me, or are humans the losers here?

 

(*) feces is a word scientists developed so they could still swear, but nobody else would be offended by it. If you listen carefully in many labs around the world, you can often hear scientists whisper "feces!", when they make a mistake.

[CharonY]

First a quick question: How do gut bacteria end up in your gut? Sounds maybe like a silly question, but I always learned that your stomach (or rather the acid in it) is able to sterilize a lot of food, isn't it? So, how do these bacteria get in your gut? Wikipedia suggests it's (also?) orally.

 

The sterilization is, at best, incomplete. A bit always comes through and even a sterilized gut will be colonized over time.

 

Since up to 60% (wt) of the dry mass of feces (*) can be made up of these gut bacteria, which suggests that they grow rather quickly, and therefore must consume quite a bit of food, what do humans have to gain from it? Wikipedia suggests a whole list of useful functions... but somehow it still seems like the bacteria get the better deal here. It reads like a hijack: without the bacteria, we get sick, develop allergies and possibly even starve. They hold us hostage! So, yeah, they've got some enzymes we don't have. But how difficult can it be to evolve some additional enzymes? The only reason we don't have them, is that we've been hijacked by gut bacteria for so long (since literally forever?) that we never had to evolve them.

 

Two things. Fist of all, in a sterile environment we are likely to be able to survive without gut bacteria. Studies on mice showed that while in some cases they provide benefits, they are not essential. However, once you are outside, you will be colonized. The protective part is if you manage to establish a flora that does not kill you. The symbiotic relationship is essentially by passive protection, so to say. Regarding the co-factors that we are not able to synthesize anymore: it was the other way round. First we needed a decent gut flora to protect us from getting killed by whatever we shove down our throats. Then it became unnecessary to synthesize stuff as the gut flora is doing it for us.

 

Somehow, as a chemical engineer, it seems awfully inefficient. You have bacteria to do some work, but then you put them into a plugflow reactor, and you discard the bacteria when they're at the end. It's crap (crappy pun definitely intended). That means you must continuously grow new ones at a high cost. I mean, there's a reason that many processes try to immobilize the microorganisms: that is so you can operate the process with a minimum growth of the microorganisms, and optimize the useful functions of the microorganisms

Again, the most useful function for us is them colonizing all niches to (hopefully) outcompete harmful bacteria. A more proper similarity to bioreactors can be found in ruminant digestive systems, for example. From the bacterial viewpoint, they do not bloody care that they are efficient. The maximize their own fitness.

 

Overall, I think the viewpoint of a bioreactor (optimizing a process with disregard to fitness of the producer) is not quite helpful to understand human-gut flora-interaction. We are, as a whole, a very diverse ecosystem for bacteria. They are colonizing us and, if the ecosystems is somewhat balanced, provide mostly passive, and some active benefits. As long as we do not die they have something to grow in. And potentially they also benefit from us procreating (as they can put their progeny into ours). If we somehow reduced their fitness (i.e. by a design that would optimize it to our benefit), they would be immediately outcompeted by other bacteria that do not have that limitation (and could potentially make us sick).

In other words, we are pretty much not in direct control of our flora, similar that a forest does not control the animals living in it. We just live together and hope that everyone benefits, balancing the fitness between all involved partners.

Edited April 11, 2012 by CharonY

[CaptainPanic]

The sterilization is, at best, incomplete. A bit always comes through and even a sterilized gut will be colonized over time.

Ah, thanks. Now that I read that, I realize I could have answered that myself. Still, thanks.

 

Two things. Fist of all, in a sterile environment we are likely to be able to survive without gut bacteria. Studies on mice showed that while in some cases they provide benefits, they are not essential. However, once you are outside, you will be colonized. The protective part is if you manage to establish a flora that does not kill you. The symbiotic relationship is essentially by passive protection, so to say. Regarding the co-factors that we are not able to synthesize anymore: it was the other way round. First we needed a decent gut flora to protect us from getting killed by whatever we shove down our throats. Then it became unnecessary to synthesize stuff as the gut flora is doing it for us.

So, you agree actually. It's like a security team, or a police force. It is necessary that you pay them, so they prevent you from evil. The small evil is that you must pay for your security, to protect you from a bigger evil. I think we can see all around us that this type of security is an excellent business case... and there are examples where this can lead to a certain kind of extortion (pay for your protection, or else).

 

There are other types of bacteria who will make a host sick. They either consume too much of our food, or produce the wrong waste products or by products (any other reasons for sickness from some bad gut flora?). The bacteria we normally have behave a bit better. Still, I wouldn't be surprised if they evolved to take just so much that it doesn't kill us. I would be surprised if bacteria would not have maximized the share they take.

 

Again, the most useful function for us is them colonizing all niches to (hopefully) outcompete harmful bacteria. A more proper similarity to bioreactors can be found in ruminant digestive systems, for example. From the bacterial viewpoint, they do not bloody care that they are efficient. The maximize their own fitness.

 

Overall, I think the viewpoint of a bioreactor (optimizing a process with disregard to fitness of the producer) is not quite helpful to understand human-gut flora-interaction. We are, as a whole, a very diverse ecosystem for bacteria. They are colonizing us and, if the ecosystems is somewhat balanced, provide mostly passive, and some active benefits. As long as we do not die they have something to grow in. And potentially they also benefit from us procreating (as they can put their progeny into ours). If we somehow reduced their fitness (i.e. by a design that would optimize it to our benefit), they would be immediately outcompeted by other bacteria that do not have that limitation (and could potentially make us sick).

In other words, we are pretty much not in direct control of our flora, similar that a forest does not control the animals living in it. We just live together and hope that everyone benefits, balancing the fitness between all involved partners.

 

I completely understand why the system is like it is. I am not advocating that we design weaker gut bacteria... as you write, they would immediately be outcompeted by other bacteria. I think we're pretty much stuck with this system. Also, this system makes a lot of sense. It's very robust.

 

It's just that I had never really realized the full extent of what's going on there.

 

I'm still looking for a proper mass and energy balance. If I have time, I will search for it a bit more. Today however, I don't have too much time.

[CharonY]

The small evil is that you must pay for your security, to protect you from a bigger evil.

They either consume too much of our food, or produce the wrong waste products or by products (any other reasons for sickness from some bad gut flora?).

 

I do not think that there is that much competition with the host with regards to overall biomass under normal conditions. We are not terrible efficient in nutrient absorption so in most situations the amount consumed by bacteria is not that much, also nutrients are not necessary lost after consumption by bacteria. So I presume that looking at energy balances, you will find that we loose more to excretion than to bacterial consumption (i.e. looking a colonized vs non-colonized guts that is).

 

In addition a major contributing factor to control bacterial colonization of the small intestine (as here the majority of nutrient absorption occurs) is bowel movement. As such it is actually not wasteful but necessary to control bacterial growth and density. However, sometimes overgrowth occurs (in clinical settings it is referred to as small intestinal bacterial overgrowth), which has been linked to certain micro-nutrient limitations.

 

Other than that of course the gut is susceptible to direct invasion by pathogenic bacteria and toxins.

Edited April 12, 2012 by CharonY

[DrDNA]

Me thinks you may have it backwards Capt.

 

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Along this same train of thought, we could accuse our mitochondria of hitching a free ride.

I don't know about you, but I'd like to keep mine.

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The flora in our guts are only eating our sewage.

Waste.

Only things that our bodies did not/would not/could not digest upstream from the lower colon.

Such as complex carbohydrate fibers (eg found in bean, broccoli, carrots, among many other things etc.....).

 

We let them live there, and we get vitamins and, importantly, protection from pathogenic flora.

As long as they thrive, there is no room for the bad guys to move in to the neighborhood.

 

When they (for example, Cholera) do move in, we get diarrhea, then dehydration, loss of K and Mg, and other minerals, and then we die.

It's an awful, horrid, death.

 

Seems like a pretty good deal to me.

 

but somehow it still seems like the bacteria get the better deal here. It reads like a hijack: without the bacteria, we get sick, develop allergies and possibly even starve. They hold us hostage!

 

They could be eating something else somewhere else in which case we would all be dead.

We need them a lot more than they need us.

 

You have bacteria to do some work, but then you put them into a plugflow reactor, and you discard the bacteria when they're at the end. It's crap (crappy pun definitely intended). That means you must continuously grow new ones at a high cost.

 

At their cost.

It is their metabolism that they are using, not ours.

And the energy comes from our garbage. Not some something that we could otherwise be using.

 

 

It is all quite efficient.

I wish that our municipal waste systems (i mean organic matter that goes into landfills---not sewage treatment, which is approximately the same principle) were 1/10 as efficient.

 

 

PS:

I'm still looking for a proper mass and energy balance. If I have time, I will search for it a bit more. Today however, I don't have too much time.

 

You might not find it.

Other than as a semiperm absorptive barrier, the gut is pretty much considered to be external to mammalian physiology for most purposes. Sort of like the skin.

At least that is what I was taught millennia ago....

Edited April 12, 2012 by DrDNA

[CharonY]

We need them a lot more than they need us.

I think this is also not quite a correct viewpoint. Or rather thinking in terms of who needs whom more is rather moot. They are adapted to the environment that we provide for them. If we were not there, they would (to state the obvious) be no gut bacteria.

 

In a way it is just an association that just happened, they adapted to us and we adapted to them. Due to selective pressures the whole systems is remarkably well balanced, especially considering the competing interests.

 

Regarding energy balances I was thinking that you may want to look at comparative analyses of ruminants to other grass-feeders. I am sure there is something around and that showed the increase in nutrient adsorption after that prolonged fermentation with bacteria in the digestive system of ruminants, and how much energy they gained from it. Although in this case there is of course a much stronger dependency to bacteria (and other symbionts) in nutritional terms than it is for e.g. humans.

Edited April 12, 2012 by CharonY

[DrDNA]

Yeah. I made it too complicated.

Let me just say that I love my e coli and they love me.

 

edit: no I take that back. -they can eat just about anything, but the wrong species or strain in our gut is deadly. we do need them more than they need us

Edited April 13, 2012 by DrDNA

[MonDie]

Can anyone relate this to kombucha tea? I brew it in my home.

I only have some knowledge of pro- and eukaryotic cell structure and processes.

 

Regarding energy balances I was thinking that you may want to look at comparative analyses of ruminants to other grass-feeders.

Maybe this book would help. I haven't read it yet, but it can be read for free off of this site. Many primates eat leaves and other fibrous material.

http://www.nap.edu/catalog.php?record_id=9826#toc

[Nathan Flinn]

...but somehow it still seems like the bacteria get the better deal here.

 

Every mutalism (equal exchange of costs and benefits between species) evolves out of some kind of parasitism (but not always the other way around). If the parasite is too hard on a host the fitness of the latter decreases and consequently the parasite's follows. Eventually the parasite has to contribute something to the host that will compensate for the lost fitness. And the moment the fitness of the host reaches the level of other, parasite-free, members its species, boom: mutalism.

 

Has anyone done any research on the energy balance?

 

Energy is only one way in which the bacteria can contribute. There are many metabolic processes that your cells do not carry out. For example, vitamin K, without which your blood would not clot, is produced by some of the intestinal bacteria. The energy is a currency in this case. Also, bacteria positively affect the efficiency of intestinal absorption. Again, they don't need to contribute energy if they can increase your efficiency of energy usage.

[ecoli]

Every mutalism (equal exchange of costs and benefits between species) evolves out of some kind of parasitism (but not always the other way around). If the parasite is too hard on a host the fitness of the latter decreases and consequently the parasite's follows. Eventually the parasite has to contribute something to the host that will compensate for the lost fitness. And the moment the fitness of the host reaches the level of other, parasite-free, members its species, boom: mutalism.

along those lines: http://www.nature.com/nature/journal/v449/n7164/abs/nature06198.html

 

 

Energy is only one way in which the bacteria can contribute. There are many metabolic processes that your cells do not carry out. For example, vitamin K, without which your blood would not clot, is produced by some of the intestinal bacteria. The energy is a currency in this case. Also, bacteria positively affect the efficiency of intestinal absorption. Again, they don't need to contribute energy if they can increase your efficiency of energy usage.

 

This is part of the story. The gut microbiota help tighten gap junctions in the intestinal epithelium, activate innate and adaptive immune responses - which seems to play a role in preventing everything from autoimmune disease, promote proper tissue development, and prevent the growth of pathogen. This is an emerging field of research and the possibilities seem almost endless.

 

The intestinal microbiota also happens to be the subject of my PhD research ;-)

 

Can anyone relate this to kombucha tea? I brew it in my home.

I only have some knowledge of pro- and eukaryotic cell structure and processes.

Well kombucha is a source of live bacterial and fungal cultures. Probiotics could help in the digestive process, maintain a healthy balance of gut microbes, and a range of other health benefits. However, most of the research on probiotics isn't completely refined, particular in human medical studies.

 

Yeah. I made it too complicated.

Let me just say that I love my e coli and they love me.

 

Just Fyi, E. coli/ Shigella is actually a tiny fraction of the gut microbiota. Most species in the gut are from the firmicutes and bacteroidetes phyla.

 

 

The flora in our guts are only eating our sewage.

Waste.

Only things that our bodies did not/would not/could not digest upstream from the lower colon.

Such as complex carbohydrate fibers (eg found in bean, broccoli, carrots, among many other things etc.....).

We get ~10% of our calories thanks to microbes breaking down indigestible materials. But these aren't the only things that microbes in the gut metabolize. They also contain enzyme to metabolize hormones and xenobiotic compounds targeted for excretion, bile acids, short chain fatty acids.. the list goes on.

 

 

We let them live there, and we get vitamins and, importantly, protection from pathogenic flora.

As long as they thrive, there is no room for the bad guys to move in to the neighborhood.

This isn't, strictly speaking, true. Species diversity seems to be protective against pathogenic organisms, but, like having an allelic marker associated with a disease, its only a risk factor not predetermination. Drinking contaminated water could still end up in cholera. And interestingly, there's some evidence that pertubations such as pathogenic microbes and antibiotics can permanently alter the indigenous microbiota.

 

 

They could be eating something else somewhere else in which case we would all be dead.

We need them a lot more than they need us.

Not necessarily. Certain species are highly evolved to live in the mammalian gut and have only been found there and are otherwise difficult to culture in the lab.

 

 

 

At their cost.

It is their metabolism that they are using, not ours.

And the energy comes from our garbage. Not some something that we could otherwise be using.

There actually can be costs: consider that gut microbes contain enzymes that can metabolize processed xenobiotics - such as drug and pharmaceutical agents. When these drugs are metabolized, they can have toxic effects in the intestines, sometimes even when the primary target of the drug is without side effects - http://www.ncbi.nlm.nih.gov/sites/entrez/16625200?dopt=Abstract&holding=f1000,f1000m,isrctn

 

There is a similar story with other metabolites - sometimes waste is toxic and even though the waste is processed by the liver to remove that toxicity, microbial action can have the opposite effect.

 

 

It is all quite efficient.

I wish that our municipal waste systems (i mean organic matter that goes into landfills---not sewage treatment, which is approximately the same principle) were 1/10 as efficient.

In terms of energy harvesting, mammals are actually pretty inefficient. Most of our calories go to heating our bodies, which require much higher than env't temperatures to be sustained. And even then, our feces contain a large amount of combustible material.

[Nathan Flinn]

... promote proper tissue development...

 

Very cool. Any references to that? Thanks.

 

PS: Good luck with your research. This is a great "new" field.

 

In terms of energy harvesting, mammals are actually pretty inefficient. Most of our calories go to heating our bodies, which require much higher than env't temperatures to be sustained.

 

Hmm... Not necessarily so. Mammals save energy by keeping the derivative of metabolic rate over various ranges of environmental temperatures at zero. The cost is still significant but it really depends on what part of the life cycle and the species you are focusing on. Many lizards spend energy moving from place to place to bath in the sun and then eat in environments that do not favor their heat balance. This movement costs! (Not just in kinetic energy -- which is minor -- but predominantly in unfavorable temperature gradients.)

 

This is an example of a problem that is complex mechanistically speaking but simple in economics: if an energy investment into maintaining a constant blood temperature is less then the energy obtained by consequently expended range of ground an animal can explore to obtain energy (food), then the investment was energetically good.

 

Mammals are very efficient in producing* and using the least efficient form of energy (heat). So they are efficient in harvesting energy.

 

* This, of course, is a paradox. Producing heat is, by definition, inefficient

 

 

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A proud mammal who never breaks the laws of thermodynamics.