In 1850, one in four American babies died before their first birthday, and people of all ages died of bacterial infections that could have been successfully treated today with antibiotics. Unfortunately, treatments that have effects usually have side effects, and we are seeing problems due to the overuse of antibiotics. They are given to people with viral infections for which they are useless and to food animals to improve their growth. As a result, antibiotic-resistant organisms are evolving and the development of new antibiotics is not keeping up with the threat. This is common knowledge, but we’re starting to realize that there may be other problems with antibiotics even when they are used correctly to save lives.
The rates of obesity, diabetes, asthma, food allergies, hay fever, eczema, inflammatory bowel disease, celiac disease, acid reflux disease, and esophageal cancer are all on the rise. Martin Blaser, MD, director of the Human Microbiome Program at NYU, thinks antibiotics may be to blame, either as a causal or a contributing factor. In his book Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, he describes some of the fascinating research he and others have been doing to elucidate the role of the more than 100 trillion microbes that live on and in each of us, and the possibility that antibiotics may have a causal role in several of the so-called diseases of civilization.
I learned a new word from the book: amphibiosis, the condition in which two life-forms create relationships that are either symbiotic or parasitic, depending on context. You have probably heard of Helicobacter pylori, the bacteria that earned Drs. Barry Marshall and Robin Warren a Nobel Prize in 2005 for finding it in the stomach and discovering its connection to gastritis, ulcers, and stomach cancers. We think of it as a pathologic organism that we should eliminate with antibiotics. Dr. Blaser argues that along with the harms it causes, it protects its hosts from a number of diseases.
That may sound like a crazy idea, but he provides a lot of surprising supporting evidence, as well as insights from evolutionary theory. Genetic studies have shown that humans have carried H. pylori for 100,000 years. We can trace human migration patterns with different strains: pure East-Asian strains can be found deep in the Amazon jungles while European strains predominate in South American coastal cities. Until recently it colonized virtually all children early in life; today, only 6% of American children harbor it. Nearly all adults in Africa, Asia and Latin American carry the bacteria, but only half of adults in Australia do. The reason for its declining prevalence can be explained in one word: transmission. Sanitation is better, families are smaller so kids are less likely to pick it up from siblings, and antibiotics destroy bacteria.
We are just beginning to appreciate the importance of the microbiome, the mixture of microbes that help keep us healthy. Babies get their first dose of microbes as they pass through the birth canal. Babies born by C-section are not colonized by their mother’s vaginal lactobacilli, and their microbiome only gradually comes to resemble that of vaginally born babies over the next several months. We don’t know how much this matters, but it’s certainly worth thinking about. The C-section rate varies geographically from 4% in some parts of Sweden to 80% in Rome.
H. pylori stimulates a profusion of lymphocytes and macrophages in the stomach. This is diagnosed as gastritis, but Blaser argues that maybe we should think of it as a normal immune response that attacks some pathogens and improves the ecology of the stomach for friendly microbes. The increase in T-cells is protective against diseases like asthma, especially early in life.
Carriers of H.pylori are 6 times more likely to develop stomach cancer as non-carriers, and carrying the cagA-positive strain doubles the risk.
Non-carriers have higher levels of stomach acid, have more heartburn, and are 8 times more likely to develop gastroesophageal reflux disease (GERD).
Carriers are 30-40% less likely to have asthma and are also less likely to have hay fever and skin allergies.
H. pylori affects the regulation of the hormones ghrelin and leptin. Farm animals are given antibiotics because they promote growth. Subtherapeutic antibiotic treatment (STAT) alters bacterial diversity, converts indigestible food in the intestine to useable calories, and increases body fat; and the effect is synergistic with a high-fat diet. Transferring the STAT microbiome to germ-free mice makes them fat. Studies in mice have shown that even brief exposures to antibiotics early in life can contribute to lifelong obesity. Children who got antibiotics in the first 6 months of life were fatter. And C-section births were associated with childhood obesity.
Antibiotics and C-sections
There is evidence that antibiotics early in life and C-sections increase the incidence and progression of diabetes. Patients who recently developed celiac disease are 40% more likely to have been prescribed antibiotics in the preceding months. Children who develop inflammatory bowel disease (IBD) are 84% more likely to have received antibiotics. Victims of Salmonella infections were more than 5 times as likely to have taken antibiotics in the previous month. Blaser speculates that antibiotic use might also be a contributory factor in conditions as diverse as nut allergies and autism.
Babies in the US routinely get antibiotics on the first day of life to prevent devastating gonorrheal eye infections, but the risk is low today. In Sweden, they are not treated, and there is no effect on the rate of infection. Perhaps we should reconsider.
Blaser says our microbiome evolved for good reasons and tampering with it is potentially dangerous. He is enthusiastic about the prospects of increasing our understanding of all those critters that live inside us, but he recognizes the limits of our current knowledge. He is skeptical of claims for probiotics and prebiotics, but he does support more rational antibiotic use and efforts like the Antibiotics Are Not Automatic campaign that has reduced the prescriptions of antibiotics by 26% in France.
Blaser’s book is well-written, explains the science clearly for the average reader, and includes fascinating stories and facts. This is exciting stuff! I wish I could be alive 100 years from now to see how research into the microbiome will change the practice of medicine.