Dr. Martin Blaser’s book Missing Microbes details his observations and hypotheses on how overuse and misuse of antibiotics may be the source of modern non-communicable diseases, such as diabetes, asthma, and obesity.

The maps of the U.S. colored with obesity and antibiotic prescriptions fit extremely well – and centered on my Southern homeland. Could it be that the obesity epidemic, diabetes, allergies, asthma, and other non-communicable diseases that are centered over the American South are not due to our preference for all things fried or sopped in butter and washed down with a swig of sweet tea? It’s not just due to sitting in front of screens too much. Certainly poor diet and little exercise don’t help. But could an over-use of antibiotics also be to blame?  That was the hypothesis.

Obesity Caused by Over Use of Antibiotics?

Dr. Martin Blaser from NYU’s experimental research on mice demonstrated drastic changes in the different types of gut bacteria present before and after antibiotic use. More strikingly, when the antibiotic use was discontinued and the bacterial populations rebounded, the bacterial types that did come back were different metabolically. Antibiotics drastically effected the gut microbiome. Does antibiotic somehow set us on a path towards obesity and diabetes?

Marti recounted trips with his wife, Dr. Maria Gloria Bello-Dominguez, another microbiome scientist [1-5], to the Yucatán. They had last visited a decade ago. Unlike the children years ago, the children walking down the road this time were obese. These scientists saw antibiotics on the shelves at convenience stores. Residents said that they took antibiotics for any number of different ailments. Shockingly, another colleague also noticed that the children in Ghana no longer had trouble with malnutrition, as they did thirty years ago. Now Ghana children have trouble with obesity.

Decreased Diversity and Missing Microbes

Combining these observations with the power of next generation sequencing of the human microbiome, Marti and Gloria to begin comparing the microbiome of Amerindian peoples to those of people in the United States. The results were shocking. People in the U.S. had a less microbial diversity than did Amerindians [1]. Developed countries were seeing skyrocketing rates of diabetes, obesity, and digestive system disorders. Whereas these indigenous populations had none. Diet and an active lifestyle were usually considered to blame for increased waistlines, but there were other differences as well. Developed countries use more antibiotics, increasingly have C-sections instead of vaginal birth, have smaller family sizes and less bed sharing, reduced use of pre-mastication for infants, and decreased breastfeeding rates [6, 7]. Which of these factors have decreased the gut microbiome diversity in developed countries? Do they all?

Studies across generations within developed countries suggest that grandchildren have less bacterial diversity than their parents and grandparents. Again, there has been a huge shift in diet, daily activity, job types, family size, and medicine over those generations even in developed nations. Is the microbiome diversity decreasing in front of our eyes? Is that decrease important?

The Increase of Antibiotic Resistance

In parallel with the increase in antibiotic use and increase in non-communicable diseases has been an increase in the rise of antibiotic resistance. As antibiotics have become commonplace in cleaners, soaps, animal feed and used to treat viral infections, more bacteria are exposed to antibiotics. Increased exposure results in increased antibiotic resistance [8-10]. This resistance often occurs quickly, within a few years of the antibiotics first being used medically [11].

Bit by bit many microbiome research laboratories around the world are seeking to answer these questions. But science takes time. Simply moving from observational studies to experimental studies in lab animals takes years, much less doing any sort of work with humans. If microbiome diversity is truly the lynchpin here somehow and we are losing bacterial species and increasing antibiotic resistance – time is of the essence. With each year, more babies are born and develop the microbiome they will carry with them throughout life. Interactions between the infant’s immune system and microbiome seem to set the stage for future health. If microbiome diversity is essential for health and our lifestyle damages that diversity – it is a public health imperative that we change our habits to protect our bacterial partners. How do scientists get this important information out to the public? How can we convince parents to stop asking for antibiotics when kids have colds caused by viruses?

Communicating the Science

Dr. Blaser’s answer was simple – write. His book Missing Microbes had been out a few months. Missing Microbes examines many of the topics he mentioned in his research talk, the connection between antibiotic use and non-communicable disease, antibiotic resistance, and a decrease in microbial diversity over generations, especially in developed countries. He has also studied the bacterium Helicobacter pylori for several decades and discusses its changing interaction with its human host across development. While you may have heard of a connection between H. pylori and stomach ulcers in older people, you may not be aware that is present in at least 50% of people worldwide. Yet these people do not have ulcers. As we have sought to remove H. pylori there has been a decrease in stomach cancer, but an increase in esophageal cancer. In Missing Microbes he discusses his hypotheses about H. pylori in our evolution. Finally, he ends the book with suggested solutions to all of these issues. As he has recently been appointed Chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria, hopefully some of these suggested solutions will be implemented. Many are as simple as educating physicians and parents better. Others, such as developing new antibiotics, are more daunting. I highly recommend Dr. Blaser’s book Missing Microbes if you are interested in these topics. It’s well written, engaging, and approachable. His footnotes at the end are also interesting and provide further reading if you desire.

You never know when you’ll hear a talk or interact with someone who might set you on a different trajectory. I have to say that Dr. Blaser’s talk and our post-doc/graduate student lunch afterwards did just that. I was already very interested in human microbiome research – after all, IGS is one of the key institutes for the Human Microbiome Project. However, now I had an imperative – write. That planted the seed for my blog and science writing to pass this valuable information on to non-scientists.

Microbes After Hours Talk

If you are in the Washington, D.C. area this week – Dr. Blaser will be speaking about his book Missing Microbes at the “Microbes After Hours” chat on Thursday, January 28^th from 6-8 pm sponsored by the American Society for Microbiology. If you aren’t in the area, or don’t get a ticket, the talk will be live streamed at Microbe World starting at 6:30 pm EST. Do tune in.

What Do You Think?

Let me know in the comments section below or send an email to mostlymicrobes@gmail.com.

What do you think about the hypothesis that obesity and other non-communicable diseases are influenced by overuse of antibiotics?

Have you read Missing Microbes? If so, what were your thoughts on it?

 

I purchased my copy of Missing Microbes. If you would also like to purchase a copy, the links provided within the post’s text are Amazon Affiliate links. This means that whatever you purchase at Amazon within 24 hours of clicking on the link will provide a small commission (less than sales taxe) to support the costs of maintaining this blog. Thank you.

REFERENCES

 

1. Clemente JC, Pehrsson EC, Blaser MJ, Sandhu K, Gao Z, Wang B, Magris M, Hidalgo G, Contreras M, Noya-Alarcón Ó et al: The microbiome of uncontacted Amerindians, vol. 1; 2015.
2. Dominguez-Bello MG, Blaser MJ: Asthma: Undoing millions of years of coevolution in early life? Science Translational Medicine 2015, 7(307):307fs339-307fs339.
3. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R: Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proceedings of the National Academy of Sciences 2010, 107(26):11971-11975.
4. Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello MG: The infant microbiome development: mom matters. Trends Mol Med 2015, 21(2):109-117.
5. Mueller NT, Whyatt R, Hoepner L, Oberfield S, Dominguez-Bello MG, Widen EM, Hassoun A, Perera F, Rundle A: Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. Int J Obes 2014.
6. Cho I, Blaser MJ: The human microbiome: at the interface of health and disease. Nat Rev Genet 2012, 13(4):260-270.
7. Blaser MJ, Falkow S: What are the consequences of the disappearing human microbiota? Nat Rev Micro 2009, 7.
8. Galán J-C, Gonzalez-Candelas F, Rolain J-M, Canton R: Antibiotics as selectors and accelerators of diversity in the mechanisms of resistance: From the resistome to genetic plasticity in the beta-lactamases world. Frontiers in Microbiology 2013, 4.
9. Blázquez J, Couce A, Rodríguez-Beltrán J, Rodríguez-Rojas A: Antimicrobials as promoters of genetic variation. Curr Opin Microbiol 2012, 15(5):561-569.
10. Gillings MR: Evolutionary consequences of antibiotic use for the resistome, mobilome and microbial pangenome. Frontiers in Microbiology 2013, 4.
11. Schmidt T, Kock, Marleen M., Ehlers, Marthie M.,: Antimicrobial resistance in Staphylococci at the human–animal interface. In: Antimicrobial Resistance – An Open Challenge Edited by Ossiprandi MC; 2015.