On January 4, 2012, the FDA issued a ban on the use of cephalosporins, a class of antibiotics, in animals. The reason for that action is that the antibiotics cause the evolution of antibiotic-resistant bacteria in the animals. This is how we get periodic outbreaks of drug-resistant E. coli in ground beef and Salmonella in eggs.

So why did the FDA limit the ban to cephalosporins only? What about penicillins and tetracyclines? They are much more widely-used in farm animals and cause resistance as well. As usual, you can find the answer if you follow the money. The farm and the pharmaceutical lobbies fiercely resisted banning them and flooded Congress with lobbyists and money. To its shame, the FDA caved in.

But I digress. After you are done with the political aspect of the story, you start wondering: Why are they feeding antibiotics to the animals? The answer is surprising: the animals gain, on average, about 15% body weight, and the earlier they start, the more profound the effect. What about humans?

 

The gut flora

Colonization of the gut by bacterial cells starts at birth, and they develop into an unusually diverse adult microbial community. But we don’t all harbor the same microbiome, or the total population of microbes. About 11 years ago, Jeffrey Gordon and his colleagues at Washington University in St. Louis made a surprising discovery. The guts of obese mice and people harbor an array of microbes different from that of their lean counterparts. Even more convincing, when they gave lean mice certain gut bacteria obtained from obese mice, they became obese. So can the gut flora be manipulated with antibiotics to affect weight? The jury is still out, but there are some clues.

Martin Blaser, whose work is summarized by Elizabeth Pennisi in Science (April 1, 2011), is a microbiologist at New York University.

“He gave mice either low doses of antibiotics over long periods, akin to what farm animals receive, or short-term, high doses, more like what a sick infant or adult would get. He then compares the physiology and microbiomes of these treated rodents with those of mice raised under similar conditions but given no antibiotics. In one set of studies, the mice fed low doses of antibiotics long-term wound up with 15% more body fat than the control mice. The chubbier, antibiotic-fed mice also had about 25% more fat in their livers.

The treated mice also had a different set of bacterial species inhabiting their guts. And several hundred bacterial genes, including ones for fatty acid production, exhibited different levels of activity—some increasing, others decreasing—in these mice compared with the controls. Similar changes occur in the rodents given short pulses of antibiotics.”

What could be the mechanism of such a profound weight-change by gut bacteria? There is still no answer, but again—there are clues.

Bacteria usually don’t colonize the stomach because of the acidic environment; they just can’t survive there for longer than a few minutes. But there is one exception: Helicobacter pylori (H. pylori).

gut bacteria
Electron micrograph of H. pylori colonizing the stomach mucosa

 

The once-ubiquitous bacterium

Helicobacter pylori spreads through drinking water and, at one time, was ubiquitous throughout the world. It was shown to be related to stomach cancer and ulcer. It also reduces the release of the stomach hormone ghrelin, which regulates the hunger response. With the widespread use of antibiotics, H. pylori was largely wiped out; only 6% of the world population, mostly in the developing world, harbor the microbe in their stomach. With this disappearance, ulcer and stomach cancer rates are indeed going down. But ghrelin levels are now unchecked by H. pylori, and this could partially contribute to the obesity epidemic. Intriguing hypothesis, but definitive proof is still not available.

Just in case you are tempted to take antibiotics to control your weight, don’t try it at home. A serious complication brought on by using oral antibiotics is wiping out the normal gut flora and colonization with drug-resistant microbes. One of the most serious complication is called Pseudomembranous colitis and is caused by an overgrowth with Clostridium difficile (C. difficile). The symptoms can range from abdominal cramps to bloody diarrhea and can be life-threatening if not treated with the appropriate antibiotic. Another complication is oral thrush, a growth of yeast (Candida albicans) in the mouth.

gut bacteria
Electron micrograph of C.difficile

The lesson we can learn from this story is that we are not autonomous beings; we are intimately connected to, and dependent on, our environment. We still know precious little about this relationship, and crude attempts to alter it invariably end up badly.


Featured Photo Credit: blog.paleohackers.com

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

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