…be prepared to take some disinfectants along for the ride.

One thing that is a total geek-out for me is reading about ecology. It’s one of the areas I wish I’d taken more coursework on back in college. At the time, it didn’t much interest me–studying species interactions was boring, and molecular biology was much more interesting. I’ve pretty much flipped 180 degrees on that one. (Well, molecular biology isn’t boring, but it’s moved off its rung as a top interest). My main interest as far as ecology is concerned is microbial ecology–especially of the ecosystem we like to call human beings. I’ve discussed bacterial ecology a bit previously (see here, here, and here, for instance), and a new study is once again making us reconsider what we know about our own personal microbial flora.

A new study published in PNAS examined microbial diversity in an unusual place–the human stomach. Though it’s now accepted that bacteria such as Helicobacter pylori can live in the stomach (and cause ulcers), the image of the stomach is still a pretty sterile place: too hostile to harbor much bacterial diversity.

Well, maybe not. In the new study:

A diverse community of 128 phylotypes was identified, featuring diversity at this site greater than previously described. The majority of sequences were assigned to the Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, andFusobacteria phyla. Ten percent of the phylotypes were previously uncharacterized, including a Deinococcus-related organism, relatives of which have been found in extreme environments but not reported before in humans.

The first few in that list had been identified before by culture, so to be fair, it was known that species besides Helicobacter could live in our stomachs. The problem with using culture to identify bacteria, though, is that there are so many out there that we simply can’t get to grow on agar plates or in nutrient broth–so we’re missing a huge chunk of the diversity out there when we rely on this technique. Therefore, iIn this study, the researchers used 16sRNA sequences–a conserved gene present in all bacteria, and one commonly used in these type of molecular ecology studies. And indeed, as they mention in their discussion, fully half of the types of bacteria they found were ones that had not been cultivated. There is a problem with this method, however. Culture is good in one way: the bacteria must be alive to find them. Regular PCR (polymerase chain reaction) isn’t so discriminatory. Therefore, the possibility exists that some of the bacteria they discovered weren’t growing, or had been killed by the stomach environment, or that they were just there as a result of being ingested in recently eaten food, etc. So, while the findings must be taken with a bit of a grain of salt, the fact that many of the species were found in multiple individuals makes it more likely that they can really live there and aren’t just transiently present. (Future studies can employ different techniques to confirm this).

Going back to the findings, they mention they identified a “Deinococcus-related organism.” As they note, Deinococcus has been previously found in “extreme environments,” including radioactive waste disposal sites (as well as more mundane locations, like animal feces). Indeed, this genus has the distinction of being the most radiation-resistant of vegetative cells. One species, Deinococcus radiodurans in particular is a fascinating organism:

Among the many characteristics of D. radiodurans, a few of the most noteworthy include an extreme resistance to genotoxic chemicals, oxidative damage, high levels of ionizing and ultraviolet radiation, and dehydration. The ability to survive such extreme environments is attributed to D. radiodurans ability to repair damaged chromosomes. It is known that heat, dehydration and radiation causes double-strand breaks in chromosomal DNA. D. radiodurans will repair these chromosome fragments, usually within 12-24 hours, using a two-system process with the latter being the most crucial method….To add to the list of radiation protective traits, D. radiodurans also possess carotenoid pigments [see this post for more on that topic--T], oxygen toxicity defense enzymes, and a distinctive outer membrane. First, carotenoids, which cause red pigmentation, are thought to act as free radical scavengers, thus increasing resistance to DNA damage by hydroxyl radicals. Next, high levels of enzymes such as superoxide dismutase and catalase both play a role in effective defense mechanisms against oxygen toxicity. Finally, a cell wall forming three or more layers with complex outer membrane lipids and a thick peptidoglycan layer containing the amino acid omithine also serves to protect D. radiodurans from lethal doses of radiation.

As they refer to the sequences they found as just “Deinococcus-related,” we don’t currently know if the species they found in the sample stomachs possess any of those properties or not, but it’s certainly worth further investigation to find out. Does that thick cell wall serve to make it more acid-resistant as well? Do any of the novel bacteria types they found play a role in human disease? It’s, um, food for thought. [/rimshot]

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Comments

  1. #1 Dr Emer
    January 17, 2006

    On another note, they might be normal flora as far as the stomach is concerned. Their existence might be preventing the “take-over” of harmful bacteria which might cause disease or injury. I agree with you, more studies are needed. Thanks for exposing this often ignored realm of our anatomy.

  2. #2 Tara
    January 17, 2006

    Oh, absolutely–I’d guess that whatever’s there is more likely to be “normal” flora than anything pathogenic.

  3. #3 Dean Morrison
    January 17, 2006

    Don’t suppose they found any ‘friendly’ bacteria from ‘pro-biotic’ the yoghurt drinks that are all the rage did they Tara?
    If they do get to culture Deinococcus radiodurans then I can see a ready market for it as an ‘anti-ageing cream’.

    Since my nickname is ‘Deano’ I’m off to register a rude trade name… ;P

  4. #4 Tara
    January 17, 2006

    Re “probiotics,” they do show 2 species of Lactobacillus, which I know is marketed as such (though I’m not familiar with the particular species they found). There are also a number of oral bacteria–several species of Streptococcus, Porphyromonas, several others. Even have Haemophilus influenzae listed. I’m betting many will turn out to be ones that were just washed there with food and drink and not really thriving, but you just never know, I guess. Some of the oral bacteria are already acid-producers, so those who live in close contact with them may very well be able to survive the stomach.

  5. #5 Michael E
    January 17, 2006

    Cool stuff. Just tracking the human digestive system from one opening to the other, one can find all kinds of interesting critters. I recall that further along the digestive track, the layers and layers of microbes actually do the work of digesting our food. So what we really “eat” is microbe doo-doo!

    I’ve heard some claims that the acid levels in our stomachs are the evolutionary result of eating rotten food (since we were scavengers, too small to hunt anything on our own). My friend’s doc told him that he didn’t need stomach acid any more because the food we eat is mostly clean. On the other hand, another friend was taking some kind of medication that increased her stomach acid levels and eventually killed off all her friendly critters. She had to take antibiotics all the time to keep from becoming infected.

    Western medicine still has a lot to learn about balance.

  6. #6 Apesnake
    January 17, 2006

    This reminds me of an article I was reading not long ago about the formation of biofilms in cows (I think it was in American Scientist). Apparently, the cow does not so much eat grass as it ingests it. The bacterial biofilms eat the grass and the cows eat the gobs of bacterial mats that bloom as a result.

    While I know there would be nothing like the biofilms of cows in human stomachs, the possibility of simpler biofilms would be another reason that obtaining pure cultures might be limiting. Many of the species living inside the film would have different living conditions and appear in far different densities than those on the outer edge, making them much less likely to show up when isolated.

    It is an interesting puzzle, how to make sure you are sequencing live bacteria while ensuring that you are not killing off many of the interesting ones when culturing.

    Curse you bacteria! Reveal your secrets!

  7. #7 Paul Orwin
    January 18, 2006

    It is an interesting study, although I’d like to see how they decided that an organism was living in the stomach, as opposed to 1) passing through, as they all must do (the 10^13/g that live in the intestine, that is) or 2)killed by stomach acid, but still with some rRNA or rDNA left to detect by PCR. One possibility; give someone an oral dose of susceptible bacteria, track the persistence of the 16S signal. When it’s gone, and they haven’t eaten anything else, you’re closer to the mark. All that said, it would be surprising to me if they hadn’t found anything but helicobacter. Bacteria live everywhere! (Yay, prokaryotes!)

  8. #8 Tara
    January 18, 2006

    Apesnake–biofilsm are definintely one option. We have a similar diversity issue (though on a much grander scale) with oral bacteria. Using DNA methods, it’s estimated there are about 400 species of bacteria in the mouth, but only ~150 of those have actually been cultured and identified. Since we know many of them grow in a biofilm and are dependent on the attachment of other species of bacteria before they can proliferate (see here for example), we may need to replicate this somehow in vitro to culture them (or mimic it in some way): a challenge we’re not up to yet. No reason the same thing couldn’t be happening in the stomach.

    Paul–they didn’t differentiate that in this study. They note in their discussion, “Detection of bacterial DNA does not necessarily indicate the presence of live, resident organisms. Bacterial DNA in stomach biopsy samples might reflect the presence of bacterial cell remnants or transient bacteria.” There’s lots of follow-up work they can do; it will be interesting to see what they come up with to deal with the transient vs. real stomach colonizers issue. Like many good pilot studies, this one raises more questions than it answers!

  9. #9 Paul Orwin
    January 18, 2006

    I didn’t click to the paper at first, and now I see that it is Relman’s group at Stanford. I wrote a blog piece a while back about his id of an archaeal pathogen. His work is a fascinating intersection of ecology and med micro (prolific, as well!)… Something interesting to keep an eye on.