World War You
by Guest Blogger,
Tyler Kokjohn, Ph.D.
The 20th century began a period of notable public health improvements in which average life expectancy increased from just under 49 years to nearly 79 years today (1, 2). A combination of factors including vaccines, improved living conditions and antimicrobial drug therapies decreased the threat of early death from many infectious diseases (3). Today death is often the long term consequence of chronic conditions such as heart (cardiovascular system) disease, cancer and diabetes.
Antibiotics vanquished a number of bacterial diseases and for a while they certainly looked like miracle cures. However, while battles with infectious diseases were being won, a sign of serious trouble, drug resistance, emerged quickly. For a while steady development of new antibiotics enabled physicians to keep pace. Eventually, rising tides of resistance forced the medical community to acknowledge the miracle of antibiotic resistance might be squandered (3). Medical professionals were called on to use antibiotics judiciously and follow procedures to reduce the spread of drug-resistant microbes – more than 25 years ago. The longstanding problems have never been resolved and some are much deeper than we first imagined.
Antibiotics are often so effective at killing or suppressing it once appeared our microbial enemies were doomed. However, our petri dish models were limited and led us to underestimate the adaptive potential of bacteria. Microbes have been fighting each other with antibiotics for a long time and some had developed effective mechanisms to inactivate or eliminate them. In addition, many antibiotic resistance factors are on DNA elements that can be passed to other bacteria. What this means is that the bacterial pathogens we seek to destroy not only have access to pre-evolved antibiotic resistance genes and they are also adept at genetic plagiarism. Once one of them acquires the right genes, ruthless selection coupled with fast transfers enables rampant antibiotic resistance spread.
We have been slow to recognize that the human body is a complex and dynamic ecosystem. Our external and many internal surfaces are populated with thousands of different microbial species. We and our billions of tiny companions are mutually interdependent to a degree that is only now beginning to be understood (4). Physicians may prescribe an antibiotic to destroy a specific pathogen, but sensitive bacteria that happen to be in the neighborhood will be decimated along with the target. Antibiotic treatments may eliminate the pathogen but they also change the composition of our normal microbial flora (5). Hopefully, any disturbances are minor and temporary, but antibiotic treatment-induced alterations in gastrointestinal microbial community composition sometimes become catastrophic for the patient. Antibiotics and anti-cancer treatments that disrupt the normal microbial balance in the colon may create a situation in which overgrowth of the bacterium Clostridium difficile produces serious, sometimes fatal disease (6). Induced by medical treatment, the best hope for recovery from a disease produced by one antibiotic has been to switch to a different antibiotic and pray the patient improved. This strategy often failed and a promising new approach has been to reconstitute the normal bacterial population using fecal transplants from healthy donors (6).
We have been tossing powerful drugs into complex, interactive communities with little understanding of their potential downstream ecological consequences. Tunnel vision and a lack of appreciation for interconnections between networks have been a traditional feature of ecosystem management by humans. Our medical approaches have been successful, but several shortcomings are coming back to haunt us.
Modern animal husbandry practices provide enormous quantities of affordable foods. They also increase the threat of human disease (7). Actions taken to address economic concerns and consumer preferences may end up having important public health implications. How animals are fed, housed, handled and transported to slaughter may favor the emergence and proliferation of highly pathogenic agents like enterohemorrhagic E. coli O157:H7. Feeding corn to cattle in order to increase production efficiency promotes colonization with E. coli O157:H7 (8) and stress may enhance the growth of these pathogens (9) in herd animals held in crowded feedlots.
Using antibiotics on food animals may directly select populations of drug-resistant bacteria which might go on to infect humans (7). Worries about fostering the transfer of nasty pathogens seem well founded; millions of instances of food poisoning are caused each year by bacteria that get from our food animals into us. One strategy suggested to mitigate the threat is ensuring antibiotics currently important in the treatment of human infections are employed only under carefully regulated situations in animal husbandry (7).
Nearly 70 years ago researchers discovered that herd and flock animals fed antibiotics gained weight (10). Estimates of the amounts of antibiotics now being provided to enhance the growth of healthy animals vary (11), but it is clear the totals are substantial. The exact reason(s) behind the growth enhancement phenomenon is unclear, but it is probable the normal dynamics of gut ecology – the interplay between animal hosts, their food and the microbial populations living within them – are fundamentally altered by sub-therapeutic antibiotic treatments. We have only vague ideas as to the species composing the microbial worlds within our food animals and even less certain concepts about how they respond to antibiotic exposures.
If antibiotic feeding promotes growth in food animals, what are the human health implications? One fact is clear; persons fed antibiotics gain weight just like farm animals (10). Some scientists suspect the intermittent exposures to prescription antibiotics many of us experience are sufficient to disrupt the normal ecological balance of our digestive systems. If this idea is correct, antibiotic treatments may be contributing directly to an increasing incidence of obesity and other conditions such as diabetes and allergies (5). Some compelling results supporting this hypothesis are in hand, but antibiotic exposure is one of many factors, including diet, that could be altering our normal populations of gut microbes (12).
The war against infectious diseases has been a monumental success. However, from the microbial ecology perspective some antibiotic treatments are a scorched earth approach with global impacts. Understanding the worlds within us may lead to new strategies to prevent or cure disease without inflicting so much collateral damage on our mostly peaceful microbial partners. All of us have a stake in the outcome of World War You.
(1) D. Leonhardt. 2006. Life Expectancy Data. The New York Times, September 27, 2006. http://www.nytimes.com/2006/09/27/business/27leonhardt_sidebar.html
(2) E. Arias. 2011. National Vital Statistics Report, Volume 64, Number 11, September 22, 2015. http://www.cdc.gov/nchs/data/nvsr/nvsr64/nvsr64_11.pdf
(3) M. L. Cohen. 1992. Epidemiology of Drug Resistance: Implications for a Post-Antimicrobial Era. Science 257:1050-1055.
(4) J. E. Brody. 2014. We Are Our Bacteria. The New York Times, 14 July 2014. http://well.blogs.nytimes.com/2014/07/14/we-are-our-bacteria/?_r=0
(5) M. J. Blaser. 2016. Antibiotic Use and Its Consequences for the Normal Microbiome. Science352:544-545. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939477/
(6) P. A. Smith. 2015. Fecal Transplants Made (Somewhat) More Palatable. The New York Times, 9 November 2015. http://www.nytimes.com/2015/11/10/health/fecal-transplants-made-somewhat-more-palatable.html
(7) Antibiotic Use in Food-Producing Animals. National Antimicrobial Resistance Monitoring System for enteric Bacteria, Centers for Disease Control and Resistance. http://www.cdc.gov/narms/animals.html
(8) T. R. Callaway et al. 2009. Diet, Escherichia coli O157:H7 and Cattle: A Review After 10 Years.Current Issues in Molecular Biology 11:67-80. http://www.horizonpress.com/cimb/v/v11/67.pdf
(9) L. Galland. 2014. The Gut Microbiome and the Brain. Journal of Medicinal Food 17(12):1261-1272. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259177/
(10) P. Kennedy. The Fat Drug. The New York Times, 8 March 2014. http://www.nytimes.com/2014/03/09/opinion/sunday/the-fat-drug.html
(11) T. F. Landers et al. 2012. A Review of Antibiotic Use in Food Animals: Perspective, Policy and Potential. Public Health Reports 127(1):4-22. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234384/
(12) T. Kokjohn. 2016. Food for Thought? https://jayvay.wordpress.com/2016/08/24/food-for-thought/