Martin Blaser, MD, director of the Human Microbiome Program at NYU has been studying the collection of bacteria in our body for over 30 years. Collectively, these are known as the human microbiome, and are the subject of Blaser’s fascinating and eminently readable new book Missing Microbes. How the overuse of antibiotics is fueling our modern plagues. Much of the research in this book is that of Blaser: he has published hundreds of peer-reviewed papers in this area over the years, but he refers to many other people’s work as well.
Cluster of bacteria live everywhere in our bodies, both on the surfaces and within, and help carry out any number of functions for our body from food digestion to disease resistance. The population of microbes varies a bit and can be changed markedly by antibiotics, and not always for the better.
For example, Blaser’s team has studied the gut bacterium heliobacter pylori, or H. pylori in great detail. As most people know, H. pylori was shown to be the cause of acute gastritis, leading to stomach ulcers by Robin Warren and Barry Marshall in 1984. They received the 2005 Nobel Prize for this breakthrough work. (At the time, the microbe was called campylobacter pylori, but has been reclassified since.)
Blaser and his research group have been studying H. pylori for some years, and correlated it with the appearance of stomach cancer. However, they have also concluded that it is a normal part of the human microbiome and has a number of positive aspects as well and is present in most people all their lives. To everyone’s great surprise, patients with acid reflux (GERD) have extremely low levels of H. pylori, and in fact it seems to protect against it.
Blaser found that the people who never acquired H. pylori in their childhood or had it “knocked out” by antibiotics have high levels of acid even after age 40, when it would normally die down in those who have H. pylori. They have a different acid regulation system, and acid reflux is more common today in children who do not have this useful bacterium.
Recognizing that a “harmful” bacterium was also a “helpful” bacterium led Blaser and his colleagues to look into what happens when bacteria are removed from the human microbiome in general. For example, we all know that over the years, farmers have used subtherapeutic levels of antibiotics in farm animals to promote faster growth. We don’t know how that happens, but since farmer animals go through a “washout phase” before they are slaughtered, this was not supposed to have any health effect on consumers. Of course, this washout period was never strictly enforced and because of worries that these antibiotics were in fact in the human food chain, countries began banning this antibiotic use,
In the US in December of 2013, the FDA got 25 out of 26 manufacturers of farm antibiotics to change the labeling so that they could not be used except for disease treatment, so this is being phased out in the US as well.
So, Blaser and his colleagues began an historical study of height: when humans began to grow taller and found that it was correlated with the elimination of pathogens in the water supply as well as with living conditions. And while Blaser noted that this paper was received with “a big yawn,” they decided to look into weight as well.
So, he began to ask the question:
“If farmers can purposefully enhance the growth of their livestock by giving [them] antibiotics, what are we doing to our children when we give them many similar medications?”
Clearly these antibiotics are affecting gut microbes in some way and they begin a series of experiments on mice to see what happened. They added four different antibiotics to the water bottles of four different groups of mice. While the mice did not gain weight, all four groups had about 15% more fat than the control groups. And it didn’t matter which antibiotic they used! Careful measurements of the bacterial populations of the bacterial population in the gut of the mice showed that the proportions of each of the expected bacteria had changed significantly. Knowing that these bacteria were involved in the digestion process, it was not unreasonable to assume that these changes were significant contributors to the increase in fat cells in the mice.
In a follow-on experiment, graduate student Laurie Cox fed the antibiotics to pregnant mice, so that the pups would have the modified microbiome from the outset. Mimicking today’s higher fat diet, they fed these mice a high fat diet from the start. And while all of the mice gained more weight than those not given that diet, those fed antibiotics gain 25%-100% more [males (25%), females (100%)].
They also found in later experiments that even giving mice antibiotics for 4 to 8 weeks was sufficient for increased weight gain for their rest of their lives.
They also were able to analyze data from 14,500 pregnant women in the Avon (UK) Longitudinal Study, and found that children who received antibiotics in the first 6 month of life became fatter.
This is the status of this continuing study as the book went to press. There is a great deal more fascinating work in this book, and we will discuss one more case in a follow-on article.
Biologists we’ve talked to about this work, recognize the significance of Blaser’s ground breaking studies of the human microbiome, but point out that the causes of obesity are complex and varied and this work is only one data point among many in the continuing study of childhood obesity.
Nonetheless, it is useful to consider whether antibiotics are changing our life by modifying our gut bacteria, and despite their great value in treatment of disease, they may have some downside as well.
In any case, we chugged through this delightful and fascinating book in just a day and a half, and you should read it as well.