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The Role Antibiotics Play in Gut Dysbiosis and the Emergence of
Antibiotic-­Resistant Bacteria
Meghan McGillin
December 14, 2016

2. Introduction
Early History of Antibiotics
The introduction of antibiotics for the treatment of disease has advanced humanity into
the era of modern medicine. Prior to Alexander Fleming’s discovery of penicillin in 1923, the
leading cause of human mortality was infectious disease [12]. Fleming set the precedent for
mass screening of potential antimicrobial species by measuring the inhibition zones in lawns of
pathogenic bacteria on the surface of agar plates. This innovative method required significantly
less resources than the traditional animal disease models, and set up the paradigm for future
pharmaceutical research [12]. Since the “golden era of discovery of novel antibiotic classes”,
which was from the 1950s through to the 1970s, no new classes have been discovered. Since
that explosive period of research and development, methods for circumventing the emergence
of antibiotic resistant bacteria have relied heavily on the modification of the already existing
antibiotic classes [12].
Current Antibiotic Use
Agricultural Use
Antibiotics are not just used to prevent and treat infections, but are also used in
low-­doses as growth promoters in livestock in the agricultural industry. For over sixty years,
antibiotics have been administered to livestock to promote weight gain, in fact, most of the
antibiotics used in the United States are used on animals, as much as 70% according to The
Union of Concerned Scientists [5] [9]. This practice has ensued colossal increases in food
animal production in the agricultural sector.
Medical Use
In terms of human health, prescription antibiotics have made historically unparalleled
advances in modern medicine [9]. Since their discovery, millions of lives have been saved.
However, now is a pivotal moment in the continuous battle against pathogenic bacteria, and
unfortunately, the current practices have produced a landscape that has allowed drug-­resistant
bacteria to thrive. A serious issue associated with this looming crisis is brought on by the
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3. crossover use of antibiotic agents in the agricultural sector as well as in disease treatment and
prevention. By undermining the microbial community’s ability to adapt and survive against our
most aggressive antibiotic drugs is the exact reason why at least 2 million people in the U.S.
become infected and at least 23,000 die from antibiotic-­resistant bacteria [14].
Antibiotic Resistance
Resistance occurs after exposure to the antibiotic drug pressures the bacteria to develop
or improve their natural defense mechanism against the bactericidal agent. This resistance
hinders the drug’s effectiveness, allowing infections to persist, which introduces the risk of
dissemination of the drug-­resistant gene into the environment [12]. Bacteria can develop
resistance through genetic mutations or by acquiring new genes through lateral transfer, which
protects them from the drug and results in a reduction or, sometimes, an elimination of the
antimicrobial effect [16]. This resistant gene is not always limited to one drug, there are strains
of bacteria, termed “super-­bugs”, that have developed resistance to multiple antibiotics and are
a serious threat to treatment of preventable infections and diseases. Without effective
antibiotics, we lose a concerning amount of treatment options for infections and illness brought
on by pathogenic bacteria. This is evident in the 63,000 deaths of hospital acquired bacterial
infections that take place in the United States, alone. In the European Union (EU), which has
banned antibiotic use as growth promoters in animal feed for the past decade, still has 25,000
human fatalities resulting from an infection with the selected multidrug resistant bacteria each
year [13][16].
The agricultural industry and medical industry argue over who is more responsible for
the concerning rise of antibiotic resistant bacteria. The food industry likes to place the blame on
the medical providers, arguing misdiagnosis on the doctor’s part and misuse by the patient are
the driving forces behind this problem. Their claims are not entirely false, in fact, there is some
strong evidence in their favor. The CDC reports as much as half of antibiotics prescribed are
used inappropriately. This could be through unnecessary use (such as with viral infections), as
well as inappropriate drug selection or incorrect doses. They also found that at least 30% of
antibiotics prescribed in an outpatient setting were unnecessary [15]. Those defending the
medical practitioners do not need to look far to divert the blame on the agricultural sector,
claiming the crux of the problem is the widespread and prolonged use of low-­dose antibiotics to
promote growth in food animals [9]. One study discovered extremely high levels of antibiotic
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4. resistance bacteria in Albanian poultry farms. Out of the 172 samples collected in this study, 91
of the bacterial isolates were of the Escherichia coli, Salmonella species or other
Enterobacteriaceae, and had demonstrated resistance to 11 different antibiotics [7]. The
effectiveness of antibiotic drugs enhances their allure, which leads to their overuse in both the
medical and agricultural industries. Another major contributing factor to the rise of resistant
pathogens is the use of broad-­spectrum antibiotics. Broad-­spectrum antibiotics kill
indiscriminately, resulting in the elimination both the pathogenic and commensal bacteria, as
well. It is theorized that many of the rising diseases and ailments may be linked to the current
use of antibiotics, and its disruption of the human gut microbiota.
The Human Microbiome
The human microbiome is this highly dynamic and essential organ that is composed of
all the microorganisms who reside coherently in the gut, skin, mouth, and other biological niches
found on and within the human host. The gut microbiota is acquired at birth, and over time
develops into a stable microbiota following the succession of key organisms [8].
The microbial community is essential for numerous biological of the host, such as aiding
in digestion and some immune functions, as well as facilitating nutrient absorptions [5]. The
commensal microbes have co-­evolved with their human host, resulting in a unique and highly
dynamic synergistic relationship [5]. This is evident in their ability to ferment non-­digestible
components in the host’s diet, as well as their ability to synthesize essential nutrients like
vitamins, and their mystifying role in host defense against pathogens [5]. The microbiota ability
to degrade complex polysaccharides is one of its most notable features relating to host health.
They are able to convert nondigestible carbohydrates into short-­chain fatty acids (SCFA),
specifically acetate, propionate, and butyrate [5].
Microbial Diversity
Microbial diversity is a major factor in determining the functionality of an individual’s gut
microbiota. Considering that the human gastrointestinal (GI) tract houses approximately
800–1000 different bacterial species and more than 7000 different strains, it can seem like there
are infinite variations for the configuration of an individual’s gut microbiota. The magnitude of
this diversity contributes to the challenge of developing a complete understanding of the
microbiota’s dynamic role in the host’s health and wellbeing [4].
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5. Despite the incredible amount of bacterial diversity and variation, there are observable
differences in the gut microbiota composition between obese and lean individuals. One study
compared the microbiomes of obese mice to lean mice and reported differences in energy
harvesting capabilities between the two phenotypes. It was also reported that the microbiota of
the obese mice was responsible for the increased capacity for weight gain that was absent in
the lean subjects [10]. It is believed that these discrepancies in microbial diversity materialize in
the form of different functional genes, which in turn, initiate different metabolic activities,
resulting in the expression of the two different phenotypes [5]. Overall, these findings support
the significance in the composition of the gut microbiota in regards to energy harvest, and
demonstrate the significance of the composition of the gut microbiota [10].
Dysbiosis and the GM
Dysbiosis is defined as an imbalance in the composition of the gut microbiota and have
been associated with immune disorders, susceptibility to infections, and metabolic diseases
such as cardiovascular diseases, obesity, and diabetes [5]. Considering the role the gut
microbiota plays in the development of obesity, one would expect perturbations within the
microbiota brought on by antibiotics to have an impact on one’s risk of obesity. It is evident that
antibiotics disrupt the composition of the microbiota, and despite the rapid recovery observed
with short term antibiotic treatment, the accumulated effect over a long period of time is
pervasive and potentially detrimental to human health in unprecedented ways.
Dysbiosis, Obesity, and Antibiotics
As discussed earlier, obesity is associated with dysbiosis, antibiotics is now believed to
accentuate this vulnerability brought on by their disruption of the gut biome ecology [3]. One
longitudinal birth cohort study found that early-­life exposure to antibiotics was linked to weight
gain [8]. Antibiotic increased the risk of being overweight by the age of 12 by 34.0%. In this
study, gender played a significant role in the weight gain observed, finding that the increased
risk of becoming overweight was only of significance among boys but not girls [8].
Another study demonstrated the repercussions of the agricultural sector’s use of
low-­dose antibiotic on host metabolism. They found that treatment of low-­dose penicillin
delivered at birth accentuated the ill-­effects of the high-­fat diet and the development of obesity
[8]. Their findings supported the idea that dysbiosis brought on by low-­level antibiotics can
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6. initiate the proliferation of specific populations within the microbiota that can promote weight
gain and obesity [6].
The consequences of antibiotic-­induced dysbiosis are not just limited to disruption of
host metabolism, but can also lead to the emergence of antibiotic-­resistant strains. Antibiotics
exert a certain kind of selective pressure on the microbial community. This leads to an across
the board reduction in the residential bacterial population, which lessens the competition for
resources for those microbes that are resistant. The resistance is often acquired through
horizontal gene transfer or genetic mutation. Regardless of the mechanism behind the acquired
resistance, the reduction in the gut microbial community creates an ideal landscape for harmful
and resistant pathogens to thrive [4]. Perhaps the greatest cause of concern from this is the
continuous flow of genetic information that occurs between different ecological compartments.
Once the resistome enters into the microbiome, antibiotic selection results in the amplification
and dissemination of these genes, which demonstrates the basis behind the concern of
antibiotic crossover between both health and agricultural sectors [12].
Conclusion
Since the “golden era of antibiotics”, nearly half a century ago, a lot has changed in the
way disease and infection is researched and understood. Antibiotic resistance is no longer an
issue limited to clinical research. It is a complex problem that requires the collaborated efforts of
microbiologists, ecologists, health care specialists, teachers, policy makers, legislative bodies,
as well as the agricultural and pharmaceutical industry in order to effectively address this
serious problem [12]. The agricultural industry needs to stop using low-­dose antibiotic to
promote livestock growth. They need to abstain from using antibiotics outside veterinary
supervision, and use alternatives to antibiotics (i.e. vaccines) when appropriate. This, in
addition, to improved hygienic conditions and overall improved animal welfare will reduce
incidences of infection and help curb antibiotic dependency. Healthcare professionals and
medical providers need to practice greater discernment for their dispersal of antibiotic
prescriptions;; additionally, they need to inform their patients about proper use and effectively
communicate the consequences of antibiotic misuse. It is the scientific community’s
responsibility to invest in researching new antibiotics and better alternatives, as well as, develop
better diagnostic tools and alternative methods towards preventing and treating infection. Policy
makers can contribute by implementing a thorough and explicit national action plan to combat
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7. antibiotic resistance. They need to call for improved surveillance methods of antibiotic-­resistant
infections and tighter regulation the proper use of antimicrobial medicines. Most importantly,
there is a dire need for educators and teachers to inform the general public on the impact of
antibiotic resistance.
The full extent of the long-­term consequences of the United States explosive and
haphazard practice of antibiotics remains unknown, but what has been made evident is the
interminable adaptive capabilities of bacteria, and their hardiness proves that they are not to be
underestimated. At this point, it seems inevitable that the US will follow in the EU’s footsteps
with the banning of growth-­promoting antibiotic use in livestock. This will require new measures
to limit the occurrence and distribution of antibiotic resistance from agricultural sources.
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