Kevin Hugins research paper. Meriam-Webster defines endocrinology as “a branch of medicine concerned with the structure, function, and disorders of the endocrine glands.” When considering the human endocrine system, most people think of endocrine glands such as the hypothalamus, pituitary, gonads, adrenals, and pancreas. No one would deny that hormones released from endocrine glands have a powerful effect on cell function throughout the human body. A relatively new field of study called Microbial Endocrinology suggests that the interactions and effects of the human endocrine system involve more organisms than just the human.

1. Microbial Endocrinology
Kevin Hugins
Biology 414-001
Kebret Kebede, M.D.
Nevada State College
Fall 2014

2. Hugins1
Abstract
In choosing a topic for this paper I first typed “endocrinology research paper topics” into
Google. As I browsed the topics, there was nothing that really excited me. Trying to brainstorm,
I asked myself what really interested me. Most of the research papers I have written have been
related to topics about viruses or bacteria. Pathogenic microorganisms seem to be the common
theme for me. The topics that have always caught my attention in classes have been about tiny
little critters that do amazingly big things. On a whim I changed my search to “endocrinology
and bacteria.” To my surprise I learned that there is something known as “Microbial
Endocrinology.” Microbial Endocrinology is defined as the study of the ability of
microorganisms to both produce and recognize neurochemicals that originate either within the
microorganisms themselves or within the host they inhabit. It seeks to understand how hosts and
microorganisms interact, leading to either health or disease. I knew I could count on those little
buggers. They seem to have their cilia in everything.

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Meriam-Webster defines endocrinology as “a branch of medicine concerned with the
structure, function, and disorders of the endocrine glands.” When considering the human
endocrine system, most people think of endocrine glands such as the hypothalamus, pituitary,
gonads, adrenals, and pancreas. No one would deny that hormones released from endocrine
glands have a powerful effect on cell function throughout the human body. A relatively new
field of study called Microbial Endocrinology suggests that the interactions and effects of the
human endocrine system involve more organisms than just the human. Just over 20 years ago,
Mark Lyte gave a presentation at the 1992 American Society for Microbiology General Meeting
suggesting that bacteria recognize human stress hormones and can alter their behavior
accordingly. Two people attended Lyte’s presentation that day. Fifteen years later, at the 2007
ASM General Meeting, the auditorium was filled for Lyte’s presentation on the same topic (Lyte
2009). As research into this area has expanded, scientists have demonstrated that microbes can
not only just detect hormone signals from its human host, but can in some instances also send out
signals that human hormone receptors can detect and respond to as if the signals were from the
human’s own system. Researchers have found that some microorganisms can produce
neuroendocrine hormones such as GABA, serotonin, acetylcholine, catecholamines and
melatonin (Wang 2013). The interdisciplinary approach of Microbial Endocrinology now
combines the study of microbiology, neurobiology, and endocrinology. This area of study looks
at the ways microbes and their hosts interact and how those interactions can contribute to health
or disease.
Scientists have been aware that other living organisms contain hormones that we would
consider to be human. Some insects and protozoa, as well as plants such as potatoes, tomatoes,
and bananas contain the neuroendocrine hormones dopamine and norepinephrine. As research

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methods became more advanced researchers recognized that microbes are able to interact with
their host in ways that are non-infectious, non-immune mediated. It is thought that interactions
can also involve hormone mediated signaling between the microbe and host. Considering the
size of the human microbiome this ability of interspecies signaling can have significant
ramifications.
The whole of the bacterial populations that are on or in a human is called the microbiota.
Currently, the most commonly suggested ratio between human cells and the bacterial cells that
are on and in the human is 10:1. For every cell that makes up our body, there are 10 bacterial
cells that are living on or in us. The majority of these bacteria reside in the gastrointestinal tract.
They are involved in processes that are vital for humans to maintain good health. These bacteria
have evolved a symbiotic relationship with humans and are involved in tasks such as aiding
digestion, synthesizing critical nutrients such as vitamins K and D, and preventing pathogenic
microorganisms from colonizing in our gut. It has been shown that anxiety and stress can affect
the microbiota within the human gut (Wang 2013). Studies in the 1990’s demonstrated that
neuroendocrine hormones could alter virulence of bacteria and stimulate growth (Lyte 2013).
Many of the gut bacteria are recognized as being hormone responsive. These include
Escherichia coli, Salmonella, Listeria, Campylobacter, and Yersinia (Sharaff 2011). Some
microorganisms that are responsible for respiratory infection have their growth stimulated by
stress hormones. Pseudomonas aeruginosa, Bordetella pertussis, Klebsiella pneumonia, and
Bordetella bronchiseptica all experience exponential cell growth when exposed to
catchecholamines.
Some fungi, protozoa and bacteria have insulin-like receptors and molecules on their cell
surface. Bacteria such as Burkholderia cepacia, B. pseudomallei, and some species of

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Streptococcus have a large number of insulin binding proteins. If an immune response is
mounted to battle one of these bacteria it may result in the host developing insulin dependent
diabetes. If during the process of battling the infection, host immune cells interact with the
insulin-like epitopes on the bacteria, the resulting antigen receptors may then also end up
targeting human insulin receptor proteins. Autoimmunity ensues, resulting in Type I Diabetes
(Nisr 2012). In their study of insulin binding of 45 different microbial species, Nisr et al. found
that Aeromonas salmonicida, Burkholderia cenocepacia, and Burkholderia multivorans all
showed a high affinity for insulin. It is their conclusion that infections by these microorganisms
may contribute to an autoimmune response that leads to the development of insulin dependent
diabetes.
Sex steroids also have interactions with bacterial receptors. When they are in a host,
accelerated growth and antibiotic insensitivity can result from exposure to steroid hormones and
glucocorticoids (Plotkin 2003). In their study, Plotkin et al. found that increasing exposure to
testosterone and dihydrotestosterone (DHT) caused considerable acceleration in cell division in
E. coli. As levels of the corticosteroid dexamethasone were increased in S. aureus and E.
faecalis, the speed of cell division was significantly increased. When exposed to testosterone
and DHT, Pseudomonas aeruginosa demonstrated up to an eight fold increase in resistance to
the antimicrobial agent Cefepime. Enterococcus faecalis insensitivity to Meropenem resulted
from testosterone and resistance to Norfloxacin was shown as a result of exposure to DHT.
Due to hormonal differences, the gut microbiota of males and females has different
microorganisms and show different responses to stressors. This difference is influenced by
androgens. The microbiota between sexes stays relatively the same from birth until puberty. As
hormonal levels change during puberty, the gut microbiota changes between the sexes. This

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development can be reversed however with castration. Upon castration, the male stops
producing the androgens that affect the microbiota and the changes in his microbiota reverse and
become more like a female again (Yurkovetskiy 2013). By sequencing 16S rRNA genes of gut
microbiota of mice, Yurkovetskiy et al. found that prepubescent males and females have similar
microbiota. After puberty, the adult female microbiota remained fairly similar to that of the
juveniles but the male’s became significantly less diverse. If the male was then castrated, his
microbiome changed again and became more like that of the juveniles and females.
A study by Markle et al. (2013), demonstrated a correlation between testosterone levels
and certain microbe associated auto immune diseases. Noting that there was a strong female bias
toward some autoimmune diseases, Markle set out to see if it was hormonally related. In some
autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, women are more
commonly afflicted then men at younger ages. This gap begins to close as the men reach an
older age and testosterone production declines. Markle studied non-obese diabetic mice that had
insulin dependent diabetes. This autoimmune disease is more prevalent in females than males.
Markle found that castration of male mice led to increased incidence of non-obese type-1
diabetes. If females were treated with androgen, their incidence of the disease decreased (Markle
2013).
As researchers gain deeper understanding of microbial endocrinology and the
relationships between humans and their microbiota, new strategies for maintaining health and
fighting disease will be developed. One example of real world application of microbial
endocrinology can be found regarding coagulase-negative staphylococci (CoNS). CoNS is
present on our skin. It typically shows low pathogenicity. However, CoNS infections are
common in intensive care patients. CoNS biofilms form on intravenous catheters of the patients.

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Catecholamines have an exponential effect on the development of staphylococcal biofilms. The
effect is so strong that staphylococci that appear dead due to antibiotics can recover when
exposed to catecholamines. In medical settings, catecholamines are administered to patients
through intravenous catheters (Sharaff 2011). These persistent infections were actually being
caused by the heath care that was administered to the patient.
Through microbial endocrinology other treatments may be developed. As this paper has
discussed, application of these techniques may one day provide a treatment for pathogens other
than the traditional antibiotics. It may lead to techniques for dealing with auto-immune diseases.
Considering the sheer numbers of microorganisms in our microbiota and all we have yet to learn
on the molecular level, this field of research may answer questions we do not even know we
have yet. In conclusion, the next time you hear a researcher’s novel idea that seems a little bit
odd; remember Mark Lyte and the ASM General Meeting of 1992. You might just want to buy a
little stock in the company. You might be hearing the next new big idea.

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