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Microbiomes, metabolic errors and detection of performance enhancing drug abuse

2016; Wiley; Volume: 9; Issue: 1 Linguagem: Inglês

10.1111/1758-2229.12494

1758-2229

Kenneth N. Timmis, James Kenneth Timmis,

Diet and metabolism studies

Time: August, 2020 Location: The Olympic Stadium, Tokyo Occasion: immediately after the 400 m Hurdles MEN Bud, lying on the track, very winded: Ooofff! That was one helluva race! Congratulations on that fantastic spurt at the end! Hank, drooping and holding his sides: Thanks buddy: winning gold is just a wonderful feeling, after dreaming about it for so long. You also did great, coming in third, especially after setting such a blistering pace for most of the race. Pedro, approaching the two: Hey fellas: well done both of you! And look at those times: we all did personal bests, and all beat the previous record – we'll celebrate tonight! Bud: thanks, Pedro. Wow: look at those two over there: their heads are glowing like light bulbs! Pedro: Uh-oh: they obviously took boosters yesterday. That multivalent microbial dope-sensor product they rub on our heads before the race seems to be pretty powerful at detecting drugs in sweat. Those fellas are in for it! Hank: Yeah, and maybe others too – those with longer hair – after analysis of the fluorescence images taken by the head scanners at the start and finish lines has been completed; should only take a couple more minutes….oh yes – there's another one – he was the one who started like a bat out of hell; couldn't keep it up, though! Bud: It really is sooo embarrassing. Pedro: Well: here come the flags; time to make the lap of honour – is the best part of the event! See you guys at the party tonight! 21.00 h, same date, in the party tent of the Olympic village A fairly raucous group of male hurdlers and pole vaulters, and female swimmers and gymnasts, are enjoying beers and comfort food, after months of strict diets. Bud and Hank go outside for a smoke and join Jess, Julio and Anna. Julio turns to Bud and asks quietly: You had several ‘immediate reveals’ in your event, which was exceptional. Bud: Yes; I just hope that the follow-up tests don't identify more. Julio: What exactly are these? I know that urine and rectal samples are taken prior to the event, but I have no clue as to what is done with them. Anna: Well, they try to detect and quantify the PEDs3 chemically in the urine samples, but some of the newer ones are so active that they are dosed in tiny amounts that can't be detected by chemical analysis. But, as you know, we are covered by zillions of microbes, both on our skin and in our intestine – our so-called microbiome4 – and the different types of microbes reflect both who we are and what we eat. Well: it turns out that they also reflect what drugs we take5. A couple of years ago, some bright Dutch scientist discovered some new bugs in the faeces of athletes on super-active PEDs which could actually use the drugs as food to grow on! She got the idea that such bugs could be present in higher quantities in the faeces of people on PEDs than of other people so, by determining the numbers and proportions of these bugs in the microbiomes of athletes, it might be possible to conclude whether they are taking performance enhancers. Well: she was right, and this so-called bioassay is much more sensitive than chemical tests! Of course, the fact that we and our microbiomes are all a little different is a bit of a complication, but the mathematicians are using artificial intelligence approaches6 to iron out the interpretation wrinkles of test results. Apparently, the next challenge on the horizon seems to be the proPEDs, substances that are not performance enhancing per se, and hence not on the WADA list7, but that get converted to PEDs by the microbes in our GI tract and then absorbed. Cheats can be so ingenious, but I guess the microbiologists will figure out a way to detect the proPEDs. Bud: Yep, I guess so. But one thing I don't understand – if the bug can eat the drug, how come there is any left for performance enhancement? Anna: Good point! I asked my Czech microbiologist friend, Jan, exactly this question. Of course, some enhancers are injected, so the gut bugs do not have an impact on the actual dose given, and live off tiny amounts excreted into the gut. But, for a drug given in tablet form, the intestinal bugs can enjoy a feast before it gets absorbed by the body. In any case, the microbiome test was just the first-generation test. Our samples are being analyzed by second-generation tests. Apparently, all cells make mistakes and create toxic chemicals that they have to detoxify, if they are to survive. Because gut bugs are not accustomed to PEDs, they tend to make more mistakes when digesting them. In addition, these bugs have not yet developed efficient processes to detoxify the harmful chemicals generated. Nevertheless, it turns out that if cells can't detoxify such substances, they tend to spit them out. When this happens, the toxins kill off some gut bug types but, amazingly, become food for other, new bugs, which gather round and eat them! Detecting these new ones, and the absence of those killed by the toxins in the gut microbiome, is an even more sensitive signature of doping. Voila: the background to the current generation of microbiome PED tests! Jess: Incredible! Although I am not too thrilled having a doctor's digit poked up my rear end, it is less uncomfortable than those smart implants they tried out a couple of years ago. Anna: (wriggling uncomfortably) Ooohhh: yes! Jan tells me that some bugs able to degrade the drug-derived toxins have now been converted into light-emitting beacons that glow when mixed with faecal samples of a PED taker – more or less like the lit-up scalps we saw this morning – so this will probably lead to a third generation test! Amazing what neat ideas microbiologists come up with! Julio: Ok, but anyway, there is still the unresolved issue of those who supposedly take such drugs as medication, which is open to all kinds of abuse. Hank: Yeah: despite the WADA defining the conditions for therapeutic use exemptions7, the issue is still problematic, which is why there's an ongoing discussion about legalizing the use of PEDs8. This would, of course, eliminate at a stroke the controversy of medical credibility. But I doubt that this will happen – sorta goes against the spirit of the Games: Pelops – not to mention Zeus – must be horrified at the idea9! Jess: Ok: enough of this serious stuff – let's join the others and have some fun! Terracotta plaque showing Pelops and Hippodameia, Metropolitan Museum of Art. Authors are indebted to Antoine Danchin and Jack Gilbert for critically reading an early draft of this piece and making very useful suggestions. However, they share no responsibility for any issues that are impossibly unlikely or in questionable taste. The authors declare they have no conflicts of interest.