Coming to understand the bugs in our yogurt and in our guts

In many ways, medicine is remarkably similar to farming.  The ancient Romans and Chinese, for example, knew that rotating crops and spreading manure in their fields would vastly improve yields.  These farmers didn’t know the underlying biology, and it didn’t matter: these practices worked, and they worked well.  Often, medicine is little different.  Insulin was given before knowing that it spurred the movement of glucose transporters to the edge of muscle cells, and exactly how acetaminophen relieves headaches has remained elusive.  The bacteria that thrive in yogurt and kefir, otherwise known as probiotics, are the modern day equivalent of manure.  But researchers are beginning to get a grasp of the microbial world in our tummies.   

In a paper published last month, Jeffrey Gordon’s team at Washington University in St. Louis identified how probiotics may influence gut health.  The scientists inoculated a sterile mouse model with 15 strains of bacteria that normally reside within the human colon.  The mice were then given probiotics and studied for changes in gut function.

Source: Wikipedia.  The model bacteria e. coli viewed by electron microscopy

The most interesting finding was that the probiotics hardly changed the composition of the bugs in the gut.  That is, the beneficial bacteria didn’t simply displace the ones already residing in the animals’ intestines.  And this makes sense to Gordon, who when interviewed said that the bacterial-colonization idea was analogous to “pouring a gallon of Kool-Aid into your swimming pool and expecting it to turn red.”

Instead, the new bacteria apparently vary the gene expression of the native ones.

Human cells and all of the microbes that inhabit the body have individual sets of genes.  A combination of spontaneity, interactions with other genes, and environmental triggers causes the genome to produce chains of messenger ribonucleic acid (mRNA). The “expressed” mRNA, in turn, is converted, or “translated,” into chains of amino acids (proteins) that do all the wonderful things that cells – or bacteria – do.  If genes were sheet music, the mRNA would be the specific keys, or group of keys, that produce the distinct musical notes or chords.  Probiotics changed the frequency that the bacteria’s genes produced mRNA, like a pianist using fewer C’s and more major scales.  Different levels of gene expression, like different musical composition, produce different effects.

Source:  Wikipedia.  Gene coding a protein.

The most noticeable shift in expression was seen in genes that dictate carbohydrate metabolism, specifically molecules known as xylooligosaccharides that are commonly found in plants.  Importantly, the probiotics manipulated the same genes in the bacterial community of human subjects.  It’s these sudden manipulations that may explain the known benefits of friendly microbes.

Gut bacteria influence the entire body.  Clinical trials have consistently shown improved gut function in people taking probiotics, where the benefits are especially pronounced in those afflicted with diarrhea.  When mice are fed probiotics, the brain produces chemical critical for regulating anxiety.  Conversely, eliminating native bacteria can be detrimental.  Some scientists are considering the over-use of antibiotics as a contributor to the rising incidence of allergies, asthma, and inflammatory bowel disease because the drugs indiscriminately wipe out the pathogenic and helpful bugs.  And eating bacteria isn’t the only way to get them into the gut.

Fecal transplant is the most remarkable bacterial therapy, if not the grossest.  As the name makes obvious, the treatment takes feces and the billions of resident bacteria from one person and transplants it into someone else.  It has been used in several different conditions, but the most dramatic results have been shown in c. difficile infections, a relentless hospital acquired bug that is rapidly resisting more antibiotics.  The stomach-churning therapy resolves a whopping 9 out of 10 c. difficile cases with virtually no side effects, and apparently, no smell.  What this frontier of probiotics will evolve into, though, is still an open question. 

Both scientists and marketers are pushing the frontier of probiotics.  “Contains live active cultures” is plastered on every dairy product from yogurt to ranch dressing.  Unfortunately, promise before understanding is a simple recipe for bad nutrition.  Bacteria could become the new snake oil, like high-dose antioxidant supplements.  But microbiologist Jeffrey Gordon’s experiments offer a model to begin rigorously investigating how probiotics work, optimal combinations of bacterial strains, and appropriate doses. 

The great 20^th century physicist Richard Feynman once said that “what I cannot create, I do understand.”  It looks like the science of probiotics is taking a step in the right direction.