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venerdì 10 giugno 2016


bacteria vs humans (by @sciencemug)
by @sciencemug
The ratio between bacteria and human cells in the human body is 1 to 1 and not, as commonly thought till now, 10 to 1.
The updated estimate has been provided by three scientists from Israeli and Canadian universities in a study published on the science journal Cell.
(A pre-print version of the paper is avaiable also on bioRxiv, a free online archive for unpublished research papers in the field of life sciences).

PART 1/3

Ooooh, hallo dear English speaking-reading-hearing visitor, welcome back to me, @sciencemug, the blog/podcast/twitter account which tells science stories, masters the ancient art of napping en plein air, breeds race sloths (for adrenaline addicted betters who like to stretch as much as possible the adrenaline-producing suspense of the races) aaand which sometimes (but not this time) talks to you thanks to the voice that is kidnapped, via a voodoo-wireless trick, from a veeery very very dumb dude.
Aaand which does all of this in Eng?ish, a language that is to proper English what a sneeze is to an authentic expression of free will and a student loan is to a cascade of donuts+pizza which plunges into a pool full of prosecco, gold and diamonds (and beautiful shoes if you’re a lady) and that is surrounded by sexy half naked women/men holding signs that say: “all of this is for you [YOUR NAME], for free. Come and get it!

Today I’m gonna tell you the story of the death of a semi-scientific almost urban legend about numbers, bacteria and human cells!

RIP 10-1  (by @sciencemug)
by @sciencemug

Soo, the story goes like this: a biology student, Ron Sender, a medical doctor, Shai Fuchs and a biology professor, Ron Milo (aka the SFMs) join their efforts to debunk the myth that, in the human body, bacteria outnumber human cells by 10 to 1.
Well, in the human body… Let’s say in the human body of an healthy adult male between 20-30 years of age, weighing 70 kg (oooooh for your brain’s sake, get over all this “I don’t know the Metric System-SI gnè gnè gnè”… Look, it’s more rational, efficient and simple than yours, besides being used worldwide. Stop whining and learn it!) and 170 cm in height that scientists use as the reference human being (aka Mr. Ref) since 1975 [when The International Commission on Radiological  Protection (alias ICRP) publishes the 480 pages long “Report of the Task Group on Reference Man, ICRP Publication 23” which addresses the need to define a reference individual for the studies regarding humans and the risks and consequences of radiations exposition (1)].

Ok, let’s say that it’s true that a looot of bacteria (belonging to more than “10,000 microbial species (2))” -at least in the healthy Western population- live in and on you, and that they “inhabit just about every part of the human body (2)” (skin, up the nose, mouth, guts and so on). But the news is that the number of these microorganisms, the SFMs say, is smaller than thought.

First of all the science trio gets to the roots of the 10:1 myth, digging deep into the science literature and finding out that all the recent papers that report the 10 to 1 ratio refer to just one study published in 1977 by Savage (aaand good luck if you want to read it for free… By the way, in case you find it, please send me a copy of it).
Now, this study, the SFMs say, is a solid piece of science work, but, althoughreferenced over 1000 times in the literature often in the context of the estimate for the vast overabundance of bacteria over human cells” (Sanders et al, 2016; (P)) its 10 to 1 estimate is just a rough calculation. Above all, Sender and lab coat pals precise, it isn’t meant at all to becomethe cornerstone of an entire field(P), being this one the human microbiome field, namely the research area which sees human beings as ecosystems formed by human cells and a plethora of other life forms, mostly bacteria (i.e. the microbiota).
Moreover, our three science myth-busters add, ironically the very same 1977 Savage study refers to another paper by Luckey dated 1972 (again, good luck if you wanna read it) for the total amount of bacteria harbored by humans (FIG1).
The chain of citations (adaptation of a figure of Sander et al, 2016 paper by @sciencemug)
 FIG 1

This 1972 Luckey’s paper says that you human beings live with 1014 bacteria, assuming that your alimentary tract have a capacity of about 1liter (and thus of roughly 1kilogram) and that it contain 1011 bugs per gram (gram: see above, you “gné gné gné”) (FIG2).

by @sciencemug
by @sciencemug
[Hamlet's image is a Public Domain pic adapted by @sciencemug (source: Wikimedia Commons)]


Soooo, dear listener, being you the smart ecosystem you are, I guess you’re probably wondering why the ‘70s science guys and all the science community after ‘em focus only on the bacterial population of the alimentary tract to determine how many microbes inhabit your whole body, right? I mean, I can feel you thinking “hey, wait a min dude – sorry, pal, but technically I’m not a dude (and also non technically, I’ve to say)…- I’m much more than my mouth stomach and bowels, c’mon, I’ve a couple of lungs (just to mention something) eyes, a lot of skin, those funny thingies I can’t figure out why be there, yeah, those… I mean, really, I’ve got a lot of stuff of me other than mouth stomach and bowels!”.
Aaand yeah, you’re right dear visitor, you’re the proud owner of lungs, eyes, skin and the non-bowel rest, but, science at hand, the ‘70s lab guys were right to focus on the alimentary tract to quantify the microbiota members of the human body, and even our science myth-busters SFMs back ‘em up on this. Well, more or less.
Actually our science trio specifies that, of the whole human alimentary tract, the relevant part is only

the colon, when it comes to which is the big deal in terms of bacteria population. Ok, let’s clarify the thing. But only after the commercial!

Are you a happy ecosystem?
Are you and your bacteria DNAs BGFs (Best Genomes Forever)? 
Well, tell it to the world by wearing

by @sciencemug

Sooo, let’s understand why in 1977 scientists focus on the alimentary tract and in 2016 our SFMs guys just want to concentrate on the colon, ok?
Sender &co sieve the scientific literature to find the available data about: which parts of the human body bugs inhabit, how many they (the bugs) are in those parts (in terms of order-of-magnitude) aaand if they (the bugs) are on Tinder.
Oddly enough, our lab guys can find answers only about the first two questions
The numbers reported in the TAB that follows are the top ones. The estimates are done in different studies by scientists by multiplying the different measured bacteria’s concentrations/areal density by the volume/surface of the various organs (whoa, three “by”s in a 32 words long sentence: this means a ~10-1 by/ sentence concentration that is high enough to cause the “By-s disease”, a neurological condition which symptoms are nausea, dizziness, headache, dry mouth and a powerful urge to sign up for a creative writing class, even one of that teacher who substitutes Mr. Keating /Robin Williams at the end of “Dead Poets Society”, but in that case the fact that you are dizzy can rapresent a problem if you want to climb up your desk and the dry mouth can sort of hinder your ability to clearly say “O captain! My captain!”…).

by @sciencemug
 [The intestine (a) and stomach (b) images are Public Domain pics adapted by @sciencemug (source: Wikimedia Commons)]


Soo, guys, as you can see, of all your human parts (I mean all of ‘em, including also the “thingies” you mentioned before that are not included in the tab) colon is by far the heavy champ in terms of total amount of bacteria harbored. And, coming back to the Luckey paper of 1972, as for the rest of the alimentary tract, well, the stomach is simply too acid, the rest of the intestine too “fast flow” aaand the human mouth too small (a sewer, yeah, with saliva and dental plaque having an insanely high bacterial concentration, but saliva and dental plaque are a very limited amount of stuff, so the totality of their bugs is no big deal after all, being respectively about 1000 and 100 times lower than the colon’s one) to count.

Representation of the number of bacteria in the colon vs mouth (by @sciencemug)
Bacteria of the colon (1014; bigger colorful cube) vs dental plaque (1012; yellow cube) and saliva (1011; red cube)

Sooo dearest visitor, to sum up in our Sender et al lab guys words: “the bacterial content of the colon exceeds all other organs  by at least two orders of magnitude.(P)

Now, let’s refresh a bit what basically said so far (mine nonsensical gibberish excluded): in 1972 Luckey states that you, humans, carry around 1014 bacteria, and you’ve the smashing majority of that amount of bugs in the alimentary tract, an alimentary tract that the reasearcher assumes as having a 1liter-1kilogram capacity and a constant concentration of 1011 bacteria per gram of wet content.
Ok? Fine.
Now-two-the-reunion, our Sender lab trio of 2016 just shows that, rather than on the whole alimentary tract, it is more correct to focus just on the colon, when it comes to microbes, human body and numbers.
Ok? Ok.
Now-three-the-franchise-goes-on, it’s time for the Sender et al lab guys to recalculate and then update the total amount of bacteria per human.
The SFMs then… Ooops, time for another commercial break!

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a bacterial condo meeting (by @sciencemug)

[The E.coli image is a Public Domain pic adapted by @sciencemug (source: Wikimedia Commons)]

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First of all, the total number of bacteria (1014) in the human body is calculated in the ’70 on the assumption that the microorganisms concentration be 1x1011/gram, and that one have to consider an alimentary tract of 1liter volume (see FIG2).
Indeed the Sender 2016 lab pack stresses on the necessity of a revision of both these estimates.
Let’s start with the latter, the volume.
Sender and colleagues shows that the relevant part for the whole bugs matter is just the colon. As a consequence, they argue, the value of the volume in the calculations must be adjusted, as the colon capacity is much smaller than 1liter.
A study of 1966 (Eve et al, 1966) that uses multiple methods, including post mortem examination, reports in fact an inner colon volume of 340ml. Moreover a 2014 MRI study (3) done on 75 healty people of both sexes in the UK finds out that the number in question is 480ml.
So the good SFMs average these numbers and calculate a final 410ml inner colon volume for our fine Mr. Ref.
Now the SFMs move to the other issue, that about the update of the bacterial concentration. They check fourteen science papers spanning through more than 40 years of research (1966 to 2008) in which the basic reasonable assumption is that stool content reliably rapresent the colon content. The authors of these studies measure bugs concentration first by “direct  microscopic clump counts from diluted [stool] samples(Sanders et al, 2016 (BioArchivX); PB), and later tanks to more sophisticated techniques like DAPI staining for direct DNA visualization and FISH, the Fluorescent In Situ Hybridization where specific fluorescent probes binds to a target DNA sequence.
The SFMs come up, after all the reading, with fourteen “bacteria number/grams of wet stool” values. The mean one they calculate is slightly more than 0.9x1011 bugs/gram of wet stool (“with an uncertainty of 19% and a coefficient of variation [CV][ i.e. the variation over a population of Mr. Refs] of 46%.” (PB).
Sooo, dear visitor, at this point, besides the updated colon volume of 410ml, the world has also an updated number of about 0.9x1011 bacteria per gram that populate that very same colon. Therefore, my inquisitive visitor, to finally compute how many bacteria there’re in Mr. Ref’s colon -and thus basically in Mr. Ref tout court- well, the SFMs have only to use another piece of information from the “ICRP Publication 23” (remember? The one that defines Mr. Ref himself): the colon density. And this is 1.04gram/ml.
Aaaaand, as PiPs’ mind seems to say right here (FIG3), the resulting total number of bugs Mr. Ref has in his colon iiiiiis -drum roll- 3.9x1013 (“with an uncertainty of 24% and a [CV] of 52%.” (P)).

by @sciencemug
by @sciencemug

So basically, dear humans, there are 100 times more bacteria in/on you than stars in the Milky Way (NASA says stars are 1-4x1011).

Number of bacteria in humans vs number of stars in the Milky Way (by @sciencemug)
Number of bacteria in humans vs number of stars in the Milky Way (by @sciencemug)

Yeepppaaa! Done! A brand new value that is a factor of 10 smaller than that 1014 of the 70’s seminal studies. Above all, a number way smaller than thought till now by everybody in the human microbiome field.
Now, dear visitor, you are smart and, unlike me, you have guts with bacteria, right, and maybe those very same bacteria make your guts feel that something in this science tale is missing
And you’re right dear gut driven visitor!
‘Cause, to update the bacteria vs human cells ratio in the human body, the SFMs need to update both the numbers in the proportion,  not just the bugs one. 

Especially considering that both Luckey and Savage studies of 1972 and 1977 refer to the same source for the total number of human cells (4), that is a 1970 genetic book (Theodosius Dobzhansky; Genetics of the evolutionary process; Columbia University Press, New York, 1970).

So the brave SFMs, instead of going on holiday in the NASA’s James Web Space Telescope cleanroom, where the sterility level is impressive and you can forget anymicrobiologicalthingforawhile and just relax, instead of doing this, our three strong-willed lab coat enthusiasts start working on the real value of the other part of the above mentioned proportion, that is the number of actual human cell in a human body.
So, the SFMs do this… Oh well, this is a tale worth a whole new coming soon post, the “Bacteria vs Human Cells: 1 to 1 (FINAL) PART 2!

Till next time then, buddy. Take care of yourself… Well, of yourselves, yours and those of your bugs (at least the good ones!*)

*Tip: anyway wash your hands frequently, above all after using the restroom, and, for our Lady Hygiene’s sake, start using the damn bidet.

Sadly, once again, I have to step up and counterbalance the appalling lack of quality of this lousy cheap blog with some accurate and authentically important piece of information.
SM incredibly omitted to mention an exceptionally relevant thing while compiling the above tab with the bacterial population in the different parts of the human body.
A thing to be found in the paper (Sacco et al, 2010; (5)) Sander et al take the value of the total skin surface of the standard adult -childishly as usual named Mr. Ref by SM- from. And the thing is that, still at present, the most widely used formula to calculate the Body Surface Area (BSA) is a 100years old one, as it dates back to 1916. The formula [BSA=weight 0.425 (in kg) x height 0.725 (in cm) x 0.007184] was created by US doctor Eugene Floyd DuBois (1882-1959) and his cousin Delafeld DuBois during WWI

They cut “[p]laster of Paris moulds of [the] subjects […] into small pieces in an attempt to measure the two-dimensional surface area of the skin. Each individual’s body/skin surface area was then calculated and [the two researchers] determined that BSA was related to height and weight(5) by their formula.
Problem is the DuBois used only nine subjects for their study, one of whom was a child, and these people were living in the middle of a world war. So it is improbable the parameters of those nine persons fit in with those of the world (or just western) population of these days.
But why is all this BSA formula question so relevant? Because the formula is essential to calculate the amount of chemotherapy drugs to be given to people with cancer. “The dosage is usually determined by multiplying the patient’s BSA [usually calculated with the DuBois formula] by a constant that has been derived for each drug [during its development] (5)”.
There are new formulas to estimate the BSA, say Sacco and colleagues in their paper (5), but to date none of these, for different reasons, is as commonly accepted as the 1916 DuBois’.
To conclude, dear visitor, this stupid and utterly useless joke of a blog has neglected to bring to your vivid attention a very interesting and crucial fact. Once again. (Stupid blog…)
Best regards.
In faith

The paper this post is about (P) (PB)
P - Sender, R., Fuchs, S., and Milo, R. (2016). Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell 164, 337-340.
PB - Sender, R., Fuchs, S., and Milo, R. (2016). Revised estimates for the number of human and bacteria cells in the body. bioRxiv doi: 

1- Snyder  Chairman, W. S., Cook, M.J., Nasset E.S., Karhausen L.R., Parry Howells G., and Tipton I.H. (1975). Report of the Task Group on Reference Man Publication 23. INTERNATIONAL  COMMISSION  ON  RADIOLOGICAL  PROTECTION, ICRP 23.
2- VV.AA. (2012). NIH Human Microbiome Project defines normal bacterial makeup of the body. 
3- Pritchard, S. E., Marciani, L., Garsed, K. C., Hoad, C. L., Thongborisute, W., Roberts, E., Gowland, P. A., and Spiller, R. C. (2013). Fasting and postprandial volumes of the undisturbed colon: normal values and changes in diarrhea-predominant irritable bowel syndrome measured using serial MRI. Neurogastroenterol Motil 26, 124-130.
4- Rosner, J. L. (2014). Ten Times More Microbial Cells than Body Cells in Humans? Microbe 9, 47.
5- Sacco, J. J., Botten, J., Macbeth, F., Bagust, A., and Clark, P. (2010). The average body surface area of adult cancer patients in the UK: a multicentre retrospective study. PLoS One 5, e8933.

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