July 18, 2011 | 13
(especially if you are like a mouse, which you are)
Scientists seem to care a great deal about the health and well being of mice. Thousands of men and women with PhD’s dedicate their lives to helping mice suffering from a dozen varieties of cancer, diabetes, obesity, forms of autism and much, much more. These scientists awake in the middle of the night with bold new ideas. They dream of, if not grandeur, at least consequence, being the one to rush in at the last moment and bring an ailing rodent from the throws of death back to a healthy life. "Stand back," you can almost hear them saying, "I know mouth to mouse."
Of course, the thing about the scientists who cure mice is that after curing them they almost always kill them. Also, most scientists who study mice are not really interested in mice. In fact, it is usually the scientists who have made the mice sick in the first place, in our image so to speak. They give the mice the diseases that plague us so that in curing them they might also understand how to make us well.
The good news is that these diligent scientists sometimes really do figure out how to heal the mice. When they do, sometimes we really do begin to understand ourselves. Such may be the case in a recent study of probiotics.
Probiotics are living species (typically bacteria, though I will argue for a broader definition) taken in one form or another by animals (typically though not always humans) in order to improve their health. The great hope with probiotics is that we might eat and favor a suite of living forms that make us healthier. Stores are filled with probiotics produced and purchased on the basis of this hope. The difficulty has been actually figuring out what species of bacteria might benefit us and also how, and/or why. For the most part, the answers are. A) No one is sure. B) No one is sure and C) No one is sure.
You would be forgiven for thinking that the benefits of probiotics were well known and worked out. After all, billions of dollars of probiotics are purchased each year and books offer “the wonderful new probiotics lifestyle.” Yet, a recent review of probiotics finds that for many of the ailments for which they are used, ailments that range from cancer to yeast infections, that their benefits are still unclear1. For example, the author of the review, Barry Goldin, offers, "A systematic review of the published literature in 2005 analysing studies of probiotic treatment of adult lactose intolerance concluded that the evidence does not support the effectiveness of probiotics for treatment of this disorder (Levri et al., 2005)2." Or, "The sum total of the existing human and animal probiotics (Inflammatory Bowel Disorder) literature is preliminary and equivocal."
We know that we have living species in our lives (and in our bodies) on which we depend. If we can just help those species, or replace them with better ones we will be living happier healthier lives. I find this basic premise exciting. The difficulty is that the data themselves, data showing the effectiveness of probiotics are, to quote my five-year-old daughter "harder to find than a flea in the universe3."
Yet, sometimes you can, indeed, find a flea in the universe, if you know where to look (on a dog is a good start, but this analogy is beginning to digress…). In the case of probiotics, one needs to look no further than diarrhea. It is one of the ailments for which the benefits of at least some probiotics are most clear. To return to Goldin,
"A multicenter European based trial with 287 children aged 1-36 months from 10 countries is one of the most extensive trials investigating probiotic treatment for acute diarrhea reported (Guandalini et al., 2000). The children were experiencing moderate to severe diarrhea. The patients were randomized to be given placebo or LGG along with oral rehydration solution. The children receiving LGG had a shorter duration and decreased severity of disease along with a shorter hospital stay."
Here, LGG is the species Lactobacillus GG. That this species helps with diarrheal cases, which are a major cause of death in infants globally, is important and interesting, but how do these bacterial species actually "work?" What scientists often assume happens is that the probiotic bacteria team up with the immune system (both by boosting it and by fighting themselves) to run the disease-causing agent (in the case of diarrhea, often a rotavirus) in the gut out of town. The problem though with this assertion is that such molecular warfare by probiotic bacteria has not been very well studied, particularly in the case of specific pathogens, rather than just broad diseases (such as diarrhea). It is hard to study humans with such pathogens and their diseases, harder still to experimentally give humans diseases only to subsequently try to cure them. That is why scientists study mice. In mice, a series of new studies has finally begun to get down to the nitty gritty of probiotic success and failure.
Then, recently, a very exciting study was published by Empara Chenoll and her colleagues at the University of Valencia in Spain4. Chenoll was interested in the human pathogen, Heliobacter pylori AKA H. pylori. Though its name does not have the ring of, say, Cholera, H. pylori is bad news. It is the major cause of ulcers and a major cause of intestinal cancer in humans. If we could get rid of H. pylori, it would be good. Chenoll wondered if there were probiotic bacteria that when consumed would kill off H. pylori. Her first step was to fight H. pylori against different lineages of the bacterial species Bifidobacterium bifidum5, in petri dish versions of cage matches. The good and bad bacteria were paired in a petri dish and then allowed to fight, to the death. Chenoll then picked the toughest lineage, the one that most often killed H. pylori. That lineage, which turned out to be "CECT 7366" was the one they would introduce into mice, to save them from H. pylori, after, of course, giving them H. pylori.
When Chenoll and friends added the H. pylori and good bacteria to the mice, the rules were,
“In experimental groups A and B, … a suspension of H. pylori … was administered for three consecutive days from day 1 onwards. In group B,… a suspension … of strain CP5 was administered orally for 11 and 18 days after infection. In group A, … a placebo … was administered. On day 14, five mice from each group were killed and analyzed, and on day 21, the remaining five mice from each group were killed and analyzed.”
Or in other words, all of the mice were given H. pylori. Half of the mice were then given the probiotics, the other half weren’t. H. pylori might just win, in which case all of the mice would stay sick. Or maybe the probiotics would win, in which case the mice treated with the probiotics would get better.
In the end, what happened was what society seems to hope will happen. The mice given the probiotic bacteria got better. The probiotics killed the H. pylori (which we know because after the mice got better, the scientists, of course, killed them and checked). In the grudge match of H. pylori versus probiotics, the probiotics won, handily. And what of the weapon being used in these fights? The evidence points toward the possibility that the probiotic bacterial species, Bifidobacterium bifidum, is producing an antibiotic protein that it is using to kill the H. pylori. What is more, the probiotics, with these tiny chemical swords, appear capable of surviving the journey through a mouse stomach and into the intestines (as revealed in additional experiments) such that those of us who are like mouse (which is all of us, who are you kidding) might one day take Bifidobacterium bifidum to cure ourselves of H. pylori. Hooray.
As I think about these results, I am excited, not just for the mice but also for the humans (maybe you, maybe me) who might one day be given the probiotics that are able to kick the butt of H. pylori. We, as humans, are so good at killing other species that the idea that we might also favor a species or two, species that would help us, is lovely and rich and interesting and the right direction. Just think about all the ways, not just having to do with bacteria, that we might favor certain species, be they flowers in our gardens, birds at our feeders, good species in our guts, or even mice in their cages that make us healthy and well.
Yes, I said mice in their cages. In the end, if a probiotic is a species that when used makes us healthier maybe mice are probiotics too. As of now, although the hope of probiotic bacteria is promising, it is the mice in their millions of small rooms that have so far saved us most often. We take their lessons, in the form of pills, surgeries, and almost everything else in medicine, nearly every day. Take a mouse, as the doctors say, and call me in the morning. They can be a bitter pill, and go down best with some beer (itself, in some incarnations, a kind of probiotic: beer of health ), but nonetheless have almost certainly affected your life, for the better. As for the mice, the scientists continue to come to their rescue just in the nick of time, as though reenacting some ancient play, a drama in which we all participate even if we would rather look away.
1. Goldin, B. Probiotics and Health: From History to Future. In Probiotics and Health Claims, First Edition, edited by Wolfgang Kneifel and Seppo Salminen © 2011 Blackwell Publishing Ltd.
2. See a recent article I wrote for Natural History (secret truth about lactose) on why it is silly and wrong to call lactose intolerance a "disorder."
3. For the record, my daughter was describing why she had not yet found her shoe. The shoe was harder to find in our house than a flea in the universe. Also, for the record, this is partially because my son, now age 1.5, likes to hide shoes.
4. E. Chenoll, B. Casinos, E. Bataller, P. Astals, J. Echevarria, J. R. Iglesias, P. Balbarie, D. Ramon, S. Genoves. Novel Probiotic Bifidobacterium bifidum CECT 7366 Strain Active against the Pathogenic Bacterium Helicobacter pylori. Applied and Environmental Microbiology, 2010; 77 (4): 1335 DOI: 10.1128/AEM.01820-10
5. This is one of the very first probiotics ever studied. It was isolated in 1900 at the Pasteur Institute by Henry Tissier from a breast-fed infant and has been a work horse in the field of probiotics ever since.
About the Author: Rob Dunn is a science writer and biologist in the Department of Biology at North Carolina State University. His first book, Every Living Thing, told the stories of the sometimes obsessive, occasionally mad, and always determined, biologists who have sought to discover the limits of the living world. His new book, The Wild Life of Our Bodies, explores how changes in our interactions with other species, be they the bacteria on our skin, forehead mites or tigers, have affected our health and well being. Rob lives in Raleigh, North Carolina with his wife, two children, and lots of microbes.
The views expressed are those of the author and are not necessarily those of Scientific American.