Sunday, 2 March 2014

How Our Gut Microbes Have Shaped Our Evolution

Ancient Poop Had Antibiotic Resistance Genes, Too

There is a war going on in your guts. Mostly you won't feel a thing unless, as happens occasionally, the wrong side gains the upper hand. The war is, maybe surprisingly, not between you and the billions of bacteria that live in your gut but between them and invaders.

Our guts are unique in that each of us has our own population of bacteria and other single-celled organisms all coexisting in balance with one another but in ratios unique to each of us. We acquire our gut 'flora' very early in life - within days and week after birth - and each population quickly establishes its unique mixture, like a micro ecosystem, which is exactly what it is.

When a foreign organism enters our gut the local population actively resists it by evolving antibiotics. The invaders respond by evolving resistance and the defenders respond by evolving even stronger antibiotics.

Bacteriophage P2 using Transmission Electron Microscope (Mostafa Fatehi)
Part of this microbiome are parasitic viruses called bacteriophages, or 'phages' for short, which attach themselves to the a bacterium and inject their contents into it where they take over its reproductive system to make more phages. These then move on to infect other bacteria, often with pieces of bacterial DNA included in their genome, some of which may be genes for making antibiotics. Not all the bacteria are killed in the process otherwise the population would be wiped out in a few hours. Over the years bacteria have evolved to live with their parasites and their parasites have evolved to live with their hosts. And bacteria may well be getting something in return.

The viruses are acting as transports to spread bacterial genes through the population, carrying things like genes for antibiotic resistance. With a good supply of phages, in the presence of antibiotics, resistance will quickly spread throughout the population and, significantly, the phage population will act as a reservoir of bacterial antibiotic genes evolved in earlier times.

Scientists were fairly sure this war had been going on for millennia - from way back before we were human to before our ancestors had crawled out of the sea even, probably to a time when the first coelenterates evolved a gut and in doing so provided a new niche which microbes could exploit - but the problem was getting the evidence. Guts don't fossilize very well and even if they did, it would be impossible to know what contamination there had been from other bacteria and their viruses during decomposition. The same goes for faeces of course.

But now a team from the Research Unit on Infectious and Emerging Tropical Diseases (URMITE) in Marseille, France, led by Christelle Desnues, has analysed 14th-century human excrement from an archaeological site at "Place d'Armes", Namur, Belgium and has found that phage viruses in the faeces carried bacterial genes for antibiotic resistance from way back before we had antibiotics. These had originated in response to natural antibiotics produced in this ongoing warfare described above. It seems that our gut flora were producing these antibiotics long before we had discovered them, not for us, but for their own survival.

Coprolites are fossilized fecal material that can reveal information about ancient intestinal and environmental microbiota. Viral metagenomics has allowed systematic characterization of viral diversity in environmental and human-associated specimens, but little is known about the viral diversity in fossil remains. Here, we analyzed the viral community of a 14th-century coprolite from a closed barrel in a Middle Age site in Belgium using electron microscopy and metagenomics. Viruses that infect eukaryotes, bacteria and archaea were detected, and we confirmed the presence of some of them by ad hoc suicide PCR. The coprolite DNA viral metagenome was dominated by sequences showing homologies to phages commonly found in modern stools and soil. Although their phylogenetic compositions differed, the metabolic functions of the viral communities have remained conserved across centuries. Antibiotic resistance was one of the reconstructed metabolic functions detected.

Sandra Appelt, Laura Fancello, Matthieu Le Bailly, Didier Raoult, Michel Drancourt and Christelle Desnues; Viruses in a 14th-century coprolite; Applied and Environmental Microbiology, 7 February 2014; doi: 10.1128/AEM.03242-13


Christelle Desnues
Desnues' team also found metabolic genes for processing fats and amino acids which could hint at the reason we've evolved tolerance for them in the first place and have evolved to live with them. So, a fascinating picture is emerging: we depend on our gut flora for our health but they can run out of control if not kept in check. This is done by semi-parasitic phage viruses which, in turn, help antibiotic resistance spread quickly through the bacterial population to prevent them being killed off altogether. All three life forms, humans, bacteria and viruses, have evolved a mutual interdependence which suits the survival needs of their respective genomes.

It's as if we need these phages as part of our microbiome. We evolved as humans to house [gut phages] for the functions they provide—that’s the coolest part.

Vincent Racaniello, microbiologist,
Columbia University
The downside of this is that when we try to use antibiotics, the phage viruses have a range of antibiotic resistance genes from earlier times which can be quickly spread through the population far more quickly than if the bacteria had to evolve them anew because, actually, this phase of the system evolved more because it benefited the bacteria and the viruses than it did humans.

This is reinforced by another discovery made by Christelle Desnues: the range of antibiotics carried by these 14th-century phages was wider than is normally found today. This is believed to reflect the relatively insanitary conditions in the 14th-century compared to today and so shows evidence of evolution of our gut flora in response to a change in our environment and so, indirectly, in theirs.

Incidentally, this refutes the argument commonly used by creationists that development of antibiotic resistance in response to antibiotic use is not an example of evolution because the bacteria must have had this resistance in the first place for it to be selected for. This argument assumes that there were no antibiotics in the environment before humans discovered and mass-produced them. This is of course false. Antibiotics have been produced by microorganism since before there were ever humans and probably before there were even multicellular organisms, but the bacteria themselves don't need to retain genes for resistance to every ancient antibiotic; they have viruses that do that for them.

Curiously, creationists who use this argument see no problem with effectively arguing that their benevolent, anthropocentric god has designed bacteria so they can resist our attempts to stop them killing us. The benevolence and anthropocentricity of this intelligent designer can apparently be turned on and off at will as the argument for it requires.

So now the question for creationists who believe in this intelligent designer who made everything just for us humans:

Why would an intelligent designer design this elaborate system, which also goes on in the guts of other species, just to help us digest fats and amino acids, which can run out of control and make us ill, and which is now helping bacteria win a battle with us over antibiotic resistance? Why didn't it design a simpler, more efficient and safer system?

Answers below please.

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  1. Thank you! I learn so much from reading your articles, Rosa. Maybe especially those about evolution and genetics.

    Now after reading this one I recall that I some time ago read about the co-evolution between man and the Helicobacter pylori bacterium; se: .

    Here are two quotes from the Abstract:

    1) When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts.

    2) These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities, show that H. pylori is approximately as old as are anatomically modern humans.

    I WOULD LIKE TO HEAR Young Earth Creationists commenting on these findings. Or they just deny these findings in order to avoid cognitive dissonance?




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