Whenever I think about antibiotics, I stymie my inner Star Wars fan and admit that it’s a good thing the Force isn’t real and Art Ayers is not actually a wizened microbiologist version of Ben Kenobi. Otherwise, he’d be internally wincing every few seconds as another round of antibiotics commences somewhere in the world and a few billion flora cry out in terror and are suddenly silenced, never to be heard from again.
I jest, sort of, but this much is true: every time you take antibiotics, billions of domesticated gut flora die. As I mentioned last week, antibiotics are designed not to target human cells, but the same cannot be said for the commensal bacteria living in our guts. See, most antibiotics don’t discriminate between “good” and “bad” bacteria. They target bacteria. They aren’t us, they are foreign entities, but we wouldn’t be us without them. We need them to function properly. It’s a bit like bringing in an exterminator to kill the bugs infesting your house, and the guy ends up killing your dog and making your cat act funny, along with killing the insects. The job is done, and he technically did what you requested, but now you have to tell your kid that Buddy moved to a farm upstate to go be a sheepdog and figure out how to deal with your cat peeing on the sofa and scratching up your stomach (leaky gut, get it?). Not very fun, and not what you bargained for.
The results of a 2010 study on the lasting effects of antibiotics on one’s gut flora are rather scary. Over a 10 month period, three individuals – humans – each went on two courses of ciprofloxacin, an extremely commonly prescribed antibiotic often used to treat bone and joint infections, respiratory tract infections, gastroenteritis, endocarditis, urinary tract infections, cellulitis, infectious diarrhea, anthrax infection, typhoid fever, and skin infections to name more than a few. In other words, it’s regarded as a trusty all-purpose antibiotic, effective across all species (vets often prescribe cipro). So, what happened to the patients’ gut flora populations after taking cipro?
Three to four days into the treatment schedule, gut diversity was lost and composition was altered. What flora remained became more homogenized, and the various ratios of the more than 400 species of bacteria that live in the gut became lopsided. One week after the conclusion of each treatment, gut flora had recovered, but only slightly. It was a shade of its former self. Diversity improved, but not to original levels. Composition began to normalize, but it was incomplete. Things were stable and the diversity/composition protected from further change, but the state of flora being protected was not the same pre-cipro state.
The authors admit that these are uncharted waters. They don’t know, nor do they pretend to know, the lasting effects of hosting an altered microbiome. They don’t use the words “good” or “bad” to describe bacteria. They just know that it’s altered, and – as much as a ten month trial can tell us – perhaps for good.
I dunno – I have an inkling of an idea that maybe, just maybe, forever altering our gut flora isn’t such a hot idea. I think the researchers would agree, but they can’t say anything without knowing for sure, of course. But my inkling isn’t exactly unfounded. We do have some evidence that altered gut flora are associated with weight gain. We even have evidence that antibiotics cause weight gain. Let’s take a closer look.
Foremost, of course, is the widespread usage of antibiotics to “increase the growth” of livestock. I use quotes because what they’re really doing is making the livestock fat by disrupting the microbiome of their guts. One study even determined that eliminating routine administration of antibiotics to livestock for the purposes of increasing weight gain wouldn’t affect dietary protein availability in developing nations. My guess as to why? Antibiotics are increasing body fat accumulation on these animals, rather than purely inducing sheer hypertrophy of muscle meat – unless you know of any bodybuilders who cycle penicillin and cipro – and the resulting weight gain is coming more from fat than protein.
Other animals offer more avenues of understanding the obesity-promoting effects of altered gut flora. Like, say, mice:
A team of researchers transplanted gut bacteria from obese mice into lean mice. The lean mice enjoyed a 60% increase in body fat and a rapid, 14-day descent into insulin resistance following the gut flora alteration.
In a later study, members of that same team induced obesity in mice through diet. As they fattened, a specific type of Firmicutes bacteria bloomed – it began to overgrow in the gut. Transplanting this Firmicute into lean mice made the lean mice fat. Lean mice who received transplants from lean donors did not get fat.
Oh, and there’s also some cool evidence in humans. Those same researchers who showed that lean mice have different gut flora than fat mice and that transferring fat mice flora to lean mice made the lean mice fat studied whether this was true in humans. It is. Just like the mice, lean human guts contain more flora from the bacterial phylum of Bacteroidetes and less from the Firmicutes phylum, whereas obese human guts contain flora more heavily weighted toward Firmicutes. Furthermore, both mice and humans with “obese” gut flora (high in Firmicutes) derive more energy from food and have an increased ability to “harvest energy.”
Okay. So it seems pretty clear that gut bacteria plays a role in obesity, and there’s strong evidence that it’s a causal role. But the studies up until now have only shown that altering gut bacteria by adding flora from obese animals to the guts of lean animals makes them gain weight. The question, then, becomes whether altering gut flora via antibiotic usage can have similar effects on weight.
One Martin Blaser, an NYU microbiome researcher, believes he has the answer. Citing the 2010 study mentioned earlier and another that he authored himself, he speculates that not only does antibiotic usage permanently change our gut flora, it also promotes obesity. Blaser examined the effect of antibiotics on Helicobacter pylori, a common member of the human gut biome. While there’s evidence that H. pylori increases the risk for ulcers and gastric cancer, making it a popular target for physicians (even in asymptomatic patients) wielding a hammer made of antibiotics, it’s also been living in human guts for at least 58,000 years. You might imagine that casually flouting such an extended co-history together could have some unintended consequences. You’d be right.
Blaser used US veterans who were scheduled for upper GI endoscopies (close examination of the upper gastrointestinal tract). Of the 92 vets, 38 had no H. pylori, 44 tested positive for H. pylori, and 10 were indeterminate. 23 of the H. pylori positive were given antibiotics, and all but two had total eradication of H. pylori. So, what happened to the 21 subjects who were initially replete in H. pylori but who eradicated them through antibiotics?
They gained the most weight. Their BMIs increased by 5%, give or take 2%. The other vets had no weight change.
Leptin levels increased by 20%.
Postprandial ghrelin increased sixfold.
The ghrelin increase is the most interesting effect to me. It does a number of things, the foremost of which is to increase hunger. High levels also increase abdominal fat. So, after taking antibiotics and losing all their H. pylori, patients weren’t as satisfied after meals, they gained more weight, and the weight they gained was likely concentrated in the abdomen. Bad stuff all around. I’ve written about the dangers of belly fat before; it’s not just a matter of LGN.
Man, antibiotics as growth promoters in livestock really make sense when you put it all together. They give you all sorts of awesome stuff:
More efficient conversion of feed into energy. Lower food costs.
Higher ghrelin levels that promote greater accumulation of visceral fat. More marbling.
Now I’m kinda wishing that Art Ayers actually was a Jedi master and he could use Force Debugging to remove specific strains of bacteria from the gut (Force Choke wouldn’t work because most gut flora are anaerobes and thus don’t require oxygen; also, they have no necks).
More problems next week, plus some solutions. Thanks for reading.