An Antibiotic Alternative?

After weeks of searching, I finally found an excellent review that describes the patterns and mechanisms by which fatty acids affect gut bacteria.

Let me give some background to this unabashedly nerdy exclamation. Since summer of freshman year, I have been working on research on the effect of a mouse’s diet on the populations of bacteria that inhabit its gut. It doesn’t sound like the most exciting prospect until you pause to consider that (1) bacterial cells in/on the human body outnumber human cells 10:1, (2) bacterial genes outnumber human genes 100:1, and (3) the majority of these bacteria are concentrated in the gut. In one respect, we’re really more like clumps of bacteria walking around with some human cells mixed in.

Much research has lately been done on the effects of prebiotics (indigestible compounds that modulate levels of gut bacteria) and probiotics (living cultures of ingested bacteria—the most well-known being the Lactobacillus in our yogurt). But painfully little research has been done on the effect of fatty acids on gut bacteria populations. Frustrated by the hours of fruitless literature searches, I recently sent an email to a prominent researcher in the field, based in Belgium. He replied by relaying his belief that the reason little research has been done in this area was because very small amounts of fatty acids actually reach the colon, adding that if a fatty acid could be constructed in away so that it could reach the colon and offer beneficial effects…that would be a “breakthrough”.

It’s true that most fatty acids are absorbed in the small intestine. But that fails to explain the sweeping shifts in colon bacteria that labs such as the Gordon lab have observed in response to high-fat diets—in as little as 24 hours. Still unsatisfied, I hit PubMed once again and somehow tripped upon a fantastic paper I had previously missed.

Desbois and Smith (2009) summarize a number of studies on how different fatty acids kill bacteria in different ways. They then proceed to propose a number of possible mechanisms. Perhaps they insert themselves into the bacterial cell membrane to make it “leaky”. Perhaps they act like a detergent and dissolve it altogether. There’s also been scattered evidence that they shut down key bacterial enzymes, prevent uptake of nutrients, or cause damage with their reactive products.

Further along there’s a statement that catches my eye:

The increasing prevalence of drug-resistant bacteria as well as an enhanced appreciation for the mechanisms of drug resistance acquisition is necessitating the discovery and development of alternative anti-infectives to conventional antibiotics.

And that brings me back to freshman year, when I had borrowed a book from my research mentor (can’t remember the name of the book but it was purple) on the escalating war between bacteria and antibiotics. Humans spend years developing a new drug, only to see bacteria evolve resistance to it in a matter of days. It was a disconcerting thought to say the least, and at the time I thought that maybe the key to avoiding a losing race was to focus efforts on bolstering the natural human immune response to react to infections rather than targeting them with antibiotics.

But Desbois and Smith offer an alternative that may hold promise. Free fatty acids (FFA) have already been shown to be effective at killing pathogens on human skin, while topical antibiotics such as mupirocin are facing growing resistance. There is potential to develop creams to prevent the spread of STIs, growth of cavities, or development of acne. Fatty acids may even help us overcome the growing concern (and political nightmare) of feeding antibiotics to livestock, presenting a natural, less controversial alternative.

And the kicker? “[…] as FFAs are also active against methane-producing Archaea (methanogens) in the guts of ruminants, they could reduce emission of this important greenhouse gas.” By stopping cows from farting, fatty acids may bring us one step closer to solving the global warming problem.

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