Last night, I headed down to the beautiful Bell House in the Gowanus section of Brooklyn for this month's Secret Science Club lecture by Dr. Martin Blaser, director of NYU’s Human Microbiome Program. Dr Blaser's title for the lecture was: "While Babies Sleep and Dream, their Microbiome Never Rests"- a very sweet, poetic title.
After a brief overview of the topics he would cover, Dr Blaser opened his lecture with a slide of the changes in the Greenland ice sheets due to global warming. Just as global warming is a change in the macroenvironment, there are changes occurring in the microenvironment inside our bodies.
The lecture then proceeded to the topic of the three "Kingdoms" of life, the Bacteria, the Archaea, and the Eukarya. To put our place in the scheme of things into perspective, Dr Blaser showed a slide of the "Tree of Life" and informed us that, in comparison to the distantly related bacteria Escherichia coli and Clostridium sp., humans can count as close relatives corn and fungi.
The microbiome is ancient, niche-specific, persistent, conserved, and host specific. Ever since animals evolved, they have had microbial symbionts. In a typical human body, there are 23,000 "human" genes present, and 8 million microbial genes. Put bluntly, 99% of the genes present in your body are bacterial. Different sites around the human body have different microbial populations. The diversity of an individual's microbiomes levels out with age, with the "adult" microbiome typically being established by the age of three. The host and the symbiotic microbes co-evolve- host and symbiont send "signals" to each other.
The next topic in Dr Blaser's lecture was the stomach bacterium Helicobacter pylori. H. pylori us the dominant microorganism in the human stomach, and has been around for at least 100,000 years and has a worldwide distribution. Approximately half of the world's population plays host to H. pylori. The bacteria adhere to the stomach epithelia and form "pedestals". The bacteria produce a protein called CagA which they inject into the epithelial cells by means of molecular "syringes". As an aside, I wish to note that molecular syringes may have formed a precursor to the bacterial flagellum, a finding which torpedoed the foolish "irreducible complexity" argument posited by "Intelligent Design" creationists.
Recently, H. pylori has been rapidly disappearing in many regions of the world- this graph shows the precipitous decline in the U.S. over eighty years. Currently, only about 6% of children in the U.S. possess H. pylori symbionts.
H. pylori has been implicated in gastric cancer as well as stomach and duodenal ulcers. Men with H. pylori are more likely to develop stomach cancer than men without H. pylori. As H. pylori disappears, the incidence of gastric cancer has decreased. There's a downside, though- as H. pylori disappears, the incidence of gastric "reflux" and esophageal adenocarcinoma has increased. Reflux, which makes esophageal cancer more prevalent, was rare in the 1930s, but the incidence has been increasing with the wane of H. pylori. H. pylori is bad for the stomach, but good for the esophagus. As Dr Blaser bluntly put it, you can't win.
The next topic of the lecture involved other health effects of H. pylori. The stomach produces the hormone ghrelin, which stimulates appetite. H. pylori affects ghrelin levels. Ghrelin levels are typically high in the morning, which triggers hunger, and decrease as one is satiated. If H. pylori is eradicated, ghrelin levels tend to remain high. The elimination of H. pylori has also been implicated in increased asthma rates and may play a role in the increased incidence of food allergies. In children under fifteen, there is an inverse association between asthma and the presence of H. pylori, but there is no such association in children over the age of fifteen. Asthma rates tend to rise with courses of antibiotics administered to infants- early H. pylori infection could possibly prevent asthma. Wheezing is caused by metacholine. H. pylori makes wheezing less prevalent in infants. the bacteria in the stomach protect the lungs. H. pylori can also cause increased skin sensitization. The disappearance of H. pylori may be related to T-cell depletion and increased gastric acidity. H. pylori is good for the upper regions of the gastrointestinal tract and bad for the lower reaches of the GI tract. It's good for us early in life, but bad for us later in life. Once again, you can't win.
The next topic of the lecture was an overview of the disappearing microbiota hypothesis. A changing human ecology since the 19th century has affected the transmission and maintenance of the indigenous microbiota, and the microorganismal composition changes have an effect on health. Since the 19th century, each generation of mothers has passed fewer microbes to its children. In a cross-cultural study, the diversity of microbiota in the U.S. has been found to be lower than that in the Malawian and South American indigenous populations.
One major factor in the transmission of microbiota is the method of birth. Mothers pass their microbiota to their children through the birthing process (vaginal birth transfers a more diverse microbiota than birth by Caesarian section), through the mastication of food for their infants, through nursing, and through skin contact.
Dr Blaser then went on a slight tangent about the overuse of antimicrobials, and injected a moment of bizarre hilarity by showing an ad for an antimicrobial stapler (as an aside, I wonder if that's why Milton was so upset at losing his red Swingline). He emphatically stated that less bacteria do not equal better health.
The "antimicrobials" discussion turned to the use of antibiotics. Out of the top eight prescriptions given to children, five are for antibiotics. 41 million courses of antibiotics are administered to children yearly. This may be a factor in the rise of obesity throughout the developing world for the last thirty years. The administration of low doses of antibiotics (STAT: sub-therapeutic antibiotic treatment) promotes growth in farm animals. The earlier the antibiotics are applied, the greater the increase in growth. Studies involving mice showed no difference in weight between mice given "STAT", but the mice given antibiotics had a greater fat mass. Not only does STAT create a greater fat mass, but it also changes the host's microbiota. The microbiota change precedes the development of obesity. Liver adiposity also increases with STAT. STAT also affects lipid metabolic processes and fatty acid metabolism. The antibiotics change the composition of microbiota through Natural Selection (microbes not killed by the antibiotics proliferate when "weaker" microbes die off) The application of antibiotics also decreases the activation of the immune system's T-cells, and changes genes which regulate obesity in early life.
Besides STAT, sub-therapeutic antibiotic treatment, studies were made of PAT, pulse antibiotic therapy, the administration of antibiotics as if an infection were being treated. In these studies, it was found that three "pulses" of antibiotics were sufficient to accelerate weight gain and resulted in bigger bones with a higher mineral content. It's possible that PAT could be resulting in increases in average height.
The administration of antibiotics reduces the diversity of microbiota- with each "pulse" there is a permanent reduction in microbiota species. If an ecosystem is perturbed once, it can recover, additional perturbations cause permanent change. Perturbed equilibrium changes all "pathways" in an ecosystem. This has an implication in the development of stem cells because microbiota create a context for development. By perturbing microbiota, we could be changing metabolic, cognitive, and developmental processes. A changing microbiota also has allergic and autimmune implications- a rise in allergies and autoimmune disorders could be "collateral damage" resulting from changing microbiota.
In the Q&A session, some bastard in the audience asked Dr Blaser if the various "probiotics" on the market were of any value. He indicated that most of the probiotics on the shelf were more triumphs of marketing rather than paragons of therapeutic value. He also asserted that more narrow spectrum antibiotics were needed to prevent large scale disruptions of microbiota. In a response to a question about Fecal Transplant Therapy, he indicated that the clinical trial showed that fecal transplants are useful in treating persistent Clostridium difficile infections. As an aside, I think I could become a regular POOP donor... I'm full of the stuff! Diet can change the microbiome somewhat, but the fundamental (heh heh) "fingerprint" of the microbiome doesn't change much.
Once again, this was a top-notch lecture in a top-flight series. It was also an appropriate lecture for the Valentine's Day season, because it was a celebration of the fact that no-one is alone, ever. So... love the little buddies who travel with you wherever you go. Special thanks to Dr Blaser, Secret Science Goddesses Dorian Devins and Margaret Mittelbach, and the staff of the beautiful Bell House. They are even better than my beloved gut-buddies, and I never have to worry about them giving me ulcers.
POSTSCRIPT: Me being me, I couldn't finish this post without putting up the video for Germfree Adolescents by the late great Poly Styrene and the X-Ray Spex: