How Commensal Organisms Help Illuminate Human Phylogenetics

Jade Shepherd, Department of Biology, Howard University


Abstract

            Commensal bacteria consists of microorganisms that are present on body surfaces covered by epithelial cells and are exposed to the external environment, for example gastrointestinal. Respiratory tract, vagina, skin, etc.; some examples include, intestinal human microbiota, propionibacterium acnes, and both urinary and rectal Escherichia coli.  Usually the number of bacteria that colonizes mucosal and skin surfaces exceeds the number of cells forming on and in the human body.  Commensal organisms is the type of bacteria that co-evolves with their hosts, however, under specific conditions they are also able to overcome protective host responses and obtain pathologic effects.  The most abundant organisms are present away from the beginning of the gut, part of the distal areas.  The human intestinal microbiota encode multiple functions that impact human health, such as, metabolism of dietary substrate, prevention of pathogen invasion, immune system modulation, and provision of a reservoir of antibiotic resistance genes.  Functional metagenomics is a culture-independent technique that has been used to study environmental microorganisms, but relatively recently applied to the study of the human commensal microbiota.  Metagenomic functional screens characterize the functional capacity of a microbial community and by subjecting the metagenome to functional assays in a genetically tractable host.  Propionibacterium acnes (P. acnes) like human cells produce porphyrin, which exhibit fluorescence and make bacteria on skin visible with a Wood’s lamp.  It is clear that since P. acnes lives on the human skin surface, it should receive the same amount of radiation exposure that humans do, this may mirror the response of human cells to radiation. Escherichia coli (E. coli) is known to be uropathogenic and commensal and can be divided into four main phylogenetic groups, designated A, B1, B2, and D.  Most E. coli strains are responsible for urinary tract infections and other extraintestinal infections and these generally belong to group B2.  However, through research, phylogenetic group B2 did not just account for the majority of urinary isolates in the young women that were tested but also was dominant amongst the rectal isolates in the young women proving to be commensal as well. Despite the occurrence of recombination events, the population structure is predominantly clonal, allowing the delineation of major phylogenetic groups. The genetic structure of commensal E. coli is shaped by multiple host and environmental factors, and the determinants involved in the virulence of the bacteria may in fact reflect adaptation to commensal habitats. A better characterization of the commensal niche is necessary to understand how a useful commensal can become a harmful pathogen. Here I will highlight the functional diversity of intestinal microbiota, discussion on how metagenomics functional screens can improve our understanding between the complex community and its human host, how porphyrin may be a more accurate reflection of radiation risk and challenges/possible solutions for using the P. acnes to predict the radiation risk, comparing uropathogenic and commensal E. coli, how commensal organisms illuminate human phylogenetics, describing the population structure of commensal E. coli, the factors involved in the spread of different strains, how the bacteria can adapt to different niches and how a commensal lifestyle can evolve into a pathogenic one.

Introduction

Phylogenetics is the study of evolutionary relationships among groups of organisms which are discovered either through molecular sequencing data or morphological data matrices.  Therefore, human phylogenetics is the study of these relationships among groups of organisms found on earth that may be useful or harmful when dealing with the human body.  Healthy humans harbor an enormous and usually diverse group of bacteria and other bugs that may live in their intestines and even possibly on skin.  These organisms, usually bacteria, have occupied earth for at least 2.5 billion years.  Life on earth emerged at least 3.8 billion years ago.  All life forms containing mucosal epithelia have had to adapt to the presence of commensal microbiota in their gastrointestinal tract; this has been achieved via interactions such as symbiosis, commensalism, and pathogenicity (Seong).  During this research the main focus was on commensal organisms and how they help illuminate human phylogenetics.

All of the outer surfaces of the human body are covered with microorganisms that normally do no harm, but may be beneficial; these are commensal organisms.  These commensal organisms on the skin help to break down dying skin cells or to destroy debris secreted by the many minute glands and pores that open on the skin (Seong).  There are also many organisms in the intestinal tract that break down complex waste products into simple substances, while others help in the manufacture of chemical compounds essential to human life.  The gastrointestinal tract, the gut, and skin are all considered to be “outer” surfaces since it is formed by the in tucking of the ectoderm, or outer surface, of the body.  These areas are often heavily populated with microorganisms, most being true commensal organisms, that live in or on humans and derive their sustenance from the surface cells of the body without causing any harm; some of these microorganisms are distinguishable from disease germs.  There are also other true commensals that live in a particular tract in a human and never cause disease; however, when an environment has capability to be altered, they are capable of causing severe illness in their host, or, without harming their host, they may infect another person with a serious disease (Britannica).  Some examples of commensal organisms are propionibacterium acnes bacteria (P. acnes), for the skin,  intestinal microbiota, bifidobacterium, for the intestines, andEscherichia coli (E. coli), for the urinary and rectal tracts.  These commensal organisms either show no pathogenic traces or can be both pathogenic and commensal.  They also help the human body in an abundance of ways such as, exposure of radiation, causing disease/infection, helping with digestion, improving the gut mucosal barrier, and much more.

Propionibacterium Acnes

            The reaction of human skin commensal bacteria to environmental hazards may serve as a biomarker for prediction of the risk of environmental hazard-initiated diseases because the bacteria are exposed to the same fields of hazards as the human body.  In medicine, a biomarker is a quantitative substance in a measurable indicator in an organism, whose presence is indicative of some phenomenon such as disease, infection, or environmental exposure; for example, a biomarker may make predictions and diagnose an aggressive disease recurrence in someone who had a liver transplant.  P. acnes, part of the commensal bacterium group present on human skin, is an auto-fluorescent anaerobic bacterium.  This fluorescence is due to the presence of endogenous porphyrins.  Propionibacterium is identified on human skin in three main species: P. acnes, P. granulosum and P. avidum (Jiang).  It is said that P. acnes bacteria are the most prevalent and usually contains the most numerous among the three.  It is an opportunistic pathogen, meaning it is capable of causing disease only when the resistance is lowered, by possible drugs or other diseases.  P. acnes is also gram-positive and accounts for approximately half of the total skin microbiota; found in the sebaceous gland-rich areas of the skin, the highest level being on the face and scalp and lowest levels being the limbs (Jiang).  There are many reasons why P. acnes can range in different areas and levels, one being, that the sebaceous gland produces high amounts of lipid and fatty acids.  Although some scientists indicated P. acnes to be a harmless organism, some demonstrated that they are not only in the development of inflammatory acne lesions but also in the formation of the microcomedo.  Microcomedo is the smallest form of an acne lesion, it is the very beginning of a pore blockage; and cannot be seen with the naked eye.  P. acnes normally resides in the pores and uses sebum as a nutrient for growth.  As the sebum production increases so does the number of P. acnes bacteria in the pore.  In the microcomedo stage, the bacteria do not cause infection because they are only in the material inside the pore and not infecting the skin. 

Figure 1: Imaging auto-fluorescent P. acnes in human facial skin. Wood’s light examination, most notably on the nose and the forehead.

Figure 1: Imaging auto-fluorescent P. acnes in human facial skin. Wood’s light examination, most notably on the nose and the forehead.

Porphyrins are groups of organic compounds; several of these porphyrins play major roles in diverse process as oxygen transportation and photosynthesis.  These include: heme, protoporphyrin, coroporphyrin, and uroporphyrin which are the most common porphyrins found in the human body (Jiang).  Porphyrins are also pigmented compounds and while exposed to long wavelength ultraviolet light near 400 nm, they usually will expose red fluorescence.  In P. acnes, these organic compounds are involved in many major metabolic processes of prokaryotic and eukaryotic cells such as respiration, biological oxidation, photosynthesis, sulfate reduction, and rearrangement.  P. acnes produces porphyrins, which is evidently fluorescent under Wood’s light examination, usually notable on the nose and forehead (Figure 1).  Wood’s light examination is a procedure that uses ultraviolet light to look closely at the skin and detect bacterial or fungal skin infections. It can also detect skin pigment disorders such as vitiligio.  If your skin is normal, the light will look purple and your skin will not glow or show any spots, otherwise your skin will change colors if you have a fungal or bacterial (these are naturally luminesce under UV light) (healthline).  Scientists believe porphyrins produced by P. acnes have the capability to monitor human radiation risks.  Radiation injury can take days or weeks to present clinical manifestations and some of the delayed radiation injuries may not develop for months or years after exposure.  This delayed response can lead to delays in treatment decisions and can then result in death.  There are many fluorophores in P. acnes that potentially can be used to reflect radiation damage, these include but are not limited to the amino acids tryptophan and tyrosine, and the coenzymes NADH, NADPH, and flavins.  P. acnes as radiation biomarkers are more accurate reflection of radiation injury due to the ideas that, P. acnes resides on the human skin surface with a high density, sample collections from the skin surface is readily accessible and does not require training, the response of live P. acnes on human faces can be monitored in a real timely manner, and lastly bacterial responses to radiation are less affected by internal physiological conditions of the individual.  These accurate observations prove that P. acnes can be used to reflect radiation damage.

Gut Microbiota: Bifidobacterium

Figure 2: Gut microbiota inside the intestine. 

Figure 2: Gut microbiota inside the intestine. 

Figure 3: Gram-positive Bifidobacteria

Figure 3: Gram-positive Bifidobacteria

            The word microbiota represents an ensemble of microorganisms that resides in a previously established environment.  Humans have clusters of bacteria in different parts of the body, such as in the surface or deep layers of skin (skin microbiota), the mouth (oral microbiota), the vagina (vaginal microbiota), etc.  Gut microbiota is the name given today to the microbe population living in our intestine (Figure 2).  The development of gut microbiota starts at birth and evolves throughout our entire life, from birth to old age, and is the result of different environmental influences.  The period in which the human host is most acutely influences by the microbiota is the postnatal period, during which the germ-free neonate moves from the sterile environment of its mother’s uterus into a world full of microorganisms and during which the neonate’s mucosal and skin surfaces become gradually colonized (Bartova).  The composition of bacterial populations does not usually stabilize until after the first few years of life; during this period, the microbiota will gradually colonize the mucosal and skin surfaces of the neonate and exert effects on the development of the immune system.  There is evidence that indicates the idea that human microbial communities play a role in the pathogenesis of diseases as diverse as asthma, eczema, inflammatory bowel disease, obesity, insulin resistance, and neoplasia.  Researchers state that there is a decreased rate of early childhood infections, diabetes, and obesity in breastfed infants compared to that in the composition of the intestinal microbiota in formula-fed infant (Moore).  In breastfed infants, Bifidobacterium became the predominant group of organisms, while formula-fed infants develop a different microbial community comprised of some Bifidobacteria and large proportions of other potentially pathogenic organisms, a few examples include, staphylococcus, enterobacteria, and clostridia.  Bifidobacterium is a gram-positive, nonmotile, anaerobic bacteria (Figure 3).  This form of bacteria inhabits the gastrointestinal tract, vagina and mouth of mammals including humans; it is proved to be in Activia yogurt.  Different species or strains of the bacteria may exert a range of beneficial health effects, including the regulation of intestinal microbial homeostasis, the inhibition of pathogens and harmful bacteria that colonize or infect the gut mucosa, the repression of procarcinogenic enzymatic activities within the microbiota, and the production of vitamins (Moore).  Bifidobacterium improves the gut mucosal barrier and lowers levels of lipopolysaccharide in the intestine and discourages the growth of gram-negative pathogens in infants.  A mother’s milk tends to contain high concentrations of lactose and lower quantities of phosphate which is a pH buffer.  Therefore, when a mother’s milk is fermented by lactic acid bacteria, which includes Bifidobacteria  in the infant’s gastrointestinal tract, the pH in the stool may be reduced, making it more difficult for gram-negative bacteria to grow in breastfed infants.  If there is a decrease of Bifidobacteria in intestinal microbiota there will be an increase in other enteric flora in infancy which are linked to diseases that arise later in life such as, increased numbers of E.coli associated with the development of atopic diseases such as asthma and eczema (Oh), while a decrease in bifidobacterial counts and an increase in S. aureus are associated with overweight mothers and an increased risk of the infant becoming overweight in childhood (Bourboulis).  Data showed that understanding the interactions between the microbial communities and their human hosts may illuminate the pathogenesis of complex human diseases such as obesity, atopic disease, and autoimmune disorders.  The main characteristics of autoimmune diseases are tissue destruction and functional impairment caused by immunologically mediated mechanisms that are principally the same as those that function against pathogenic infections; both living bacteria and their components are clearly responsible for many of those immunomodulatory mechanisms (Bartova).  Immunomodulatory mechanisms have the ability to alter or regulate one or more immune factors.  Moreover, these disorders represent an important medical problem because they have a devastating impact on quality of life and require longstanding medical care.  Understanding these interactions provided a source for therapeutic approaches, a way to decrease the pathogenesis.  One method used was PCR (polymerase chain reaction) probing for specific genes and chemical profiling of microbial metabolites.  PCR is a technology in molecular biology used to amplify a single copy or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence.  These approaches have shown altered metabolic profiles in human subjects with inflammatory bowel disease, variations in the composition of the intestinal microbiota with human diet and functional differences in the gut microbiota related to host body habitus, developmental changes in the composition of the gastrointestinal microbiota during infancy and childhood, and lastly the genetic epidemiology of antibiotic resistance in the intestinal microbiota (Moore).  Specific variations in the composition of the gastrointestinal microbial community have been linked to important area of human health and disease. Through research there has been recent advances in understanding the interactions between both bacterial metabolites and the host cellular machinery, which have begun to illuminate the physiologic basis of microbial contributions to human pathology; meaning the study of human diseases.  Functional metagenomics screens may also illuminate the genetic determinants of microbial interactions with host cells.  Functional metagenomics is one of the culture-independent techniques that was used for decades to study environmental microorganisms.  It wasn’t until recently that this method was applied to the study of the human commensal microbiota.  Metagenomic functional screens characterize the functional capacity of a microbial community, independent of identity to known genes, by subjecting the metagenome to functional assays in a genetic host.  Using the screening method one can identify specific bacterial gene products that directly influence the fate of human cells.  These same screens may also be designed to investigate the immune-modulatory capacity of the gastrointestinal microbiota.  Together, these studies demonstrate the potential for functional metagenomics screens to illuminate the genetic mechanisms for microbial community contribution to the development of the human immune system and the pathogenesis of atopic, autoimmune, and neoplastic disease, which may provide novel therapeutic targets for these conditions (Moore).  Furthermore, in addition to interacting with cells found in humans, commensal bacteria such as intestinal microbiota and other organisms can also use quorum-sensing to convey signals over distances and coordinate community gene expression.  Quorum sensing is a system of stimulate and response correlated to population density.  Many species of bacteria use quorum sensing to coordinate gene expression according to the density of their local population.  With every technique presented and human disease inhibited it gives proof that human microbial communities play a role in the pathogenesis of diseases.

Urinary and Rectal Escherichia coli

            Escherichia coli (E. coli) is a gram-negative, facultative anaerobic, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms.  Most strains are harmless and live peacefully in our guts munching on bits of food and causing no harm or even creating benefits for hosts by helping with digestion, but some types can cause serious food poisoning in their hosts, causing people to experience vomiting, diarrhea, and dysentery; and in rare cases, the bacteria can lead to kidney failure or even death.  These harmful E. coli occasionally responsible for product recalls due to food contamination; it can also cause various diseases, both intestinal and extra intestinal.  E.coli is a commensal organism of humans and other warm-blooded animals.  It can also be a virulence organism; virulence factors in the bacteria depend on the variations in genetic backgrounds.  Phylogenetic studies have shown that E. coli can be divided into four main phylogenetic groups, A, B1, B2, and D (Foxman).  These groups give a better characterization of understanding how commensal bacteria or commensal E. coli can become a harmful pathogen.  Groups A and B1 are sister groups whereas group B2 is included in an ancestral branch.  These phylo-groups apparently differ in their ecological niches, life-history and some characteristics, such as their ability to exploit different sugar sources, their antibiotic resistance profiles and their growth rate (Amaral).  The majority of the E. coli strains that live and thrive in the environment belong to phylogenetic group B1.  Genome size also plays a factor amongst the phylo-groups, group A and B1 has smaller genomes than B2 and D; these two groups contained more virulence factors than strains from groups A and B1.  It is proven however, that most E. coli strains in group B2 are responsible for urinary tract infections (UTI) and other extra intestinal infections; this group also often carries virulence determinants.  Bowel flora or rectal E. coli is considered the natural reservoir of pathogenic strains in extra intestinal infections, and is therefore considered apart of the commensal strain population.  The phylogenetic distribution of commensal E. coli isolates from healthy humans could provide an important comparison and insight on the spread of the potential pathogenic lineage (Foxman).  Commensal organisms are usually dominated by strains of A and B1 groups, with few B2 strains.  However, through observation, the difference in distribution of E. coli phylogenetic groups between pathogenic and commensal E. coli populations was based on comparing fecal and urine isolates from different host populations.  Amaral and her colleagues identified phylogenetic groups of E. coli isolates from college-age women and compared their distributions among collections in order to better compare genetic relationships between pathogenic and commensal E. coli populations.  The researchers described the distributions of 93 uropathogenic strains and 88 commensal rectal strains from healthy women among the four main phylogenetic groups of E.coli (Foxman).  The results showed that the strains from group B2 dominated in UTI specimen collection and less frequently in the rectal specimen collection, and were also the most common group amongst all the results from the studied women.  They also examined genetic variability within each phylogenetic group using ERIC typing and showed that group B2 and D strains of UTI origin were genetically less diverse than those of rectal origin.  ERIC-PCR which stands for enterobacterial repetitive intergenic consensus PCR analysis was used in order to further examine the genetic diversity of strains within each phylogenetic group from each collection as shown in the results above.  Based on all the information stated, it may be safe to say or estimate that B2 strains account for a lot of all extraintesinal E. coli infections, it only accounted for a small percentage of examined commensal human strains.  Since group B2 is found in both pathogenic and commensal groups it proves there is genetic diversity.  It is possible that a healthy human population can have a high rate B2 strain but can also be less virulent. This data shows that bacteria or E. coli can adapt to different niches and move and evolve from a commensal lifestyle to a pathogenic one.  Potentially, the evolution of such organisms from their commensal ancestor not only requires the gain of additional genes, for example those that encode virulence determinants, but also the modification of existing functions.  One example of the way pathogens use their genetic variability to escape immune surveillance and drug therapy comes from 3TCresistant HIV-1; meaning HIV is resistant to 3TC which is lamivudine a potent nucleoside, and is used for treatment of chronic hepatitis B.  HIV can rapidly develop resistance to 3TC if viral loads are not suppressed below the limit of detection, therefore meaning the treatment will not work. 

Conclusion

            Porphyrins are naturally synthesized in human cells, and are also produced by human commensal bacteria such as P. acnes in human skin.  As a commensal bacterium, P. acnes is a component part of every human being; it’s constant and consistent presence on human skin may make it an excellent endogenous radiation biochemistry.  Microbiota represents an ensemble of microorganisms that resides in a previously established environment, and the development of gut microbiota starts at birth and evolves throughout our entire life, from birth to old age, and is the result of different environmental influences.  An example of such is bifidobacterium, which improves the gut mucosal barrier and lowers levels of lipopolysaccharide in the intestine and discourages the growth of gram-negative pathogens in infants.  A mother’s milk tends to contain high concentrations of lactose and lower quantities of phosphate which is a pH buffer.  Therefore, when a mother’s milk is fermented by lactic acid bacteria, which includes Bifidobacteria in the infant’s gastrointestinal tract, the pH in the stool may be reduced, making it more difficult for gram-negative bacteria to grow in breastfed infants.  E. coli in most strains are harmless and live peacefully in our guts munching on bits of food and causing no harm or even creating benefits for hosts by helping with digestion, but some types can cause serious food poisoning in their hosts, causing people to experience vomiting, diarrhea, and dysentery; and in rare cases, the bacteria can lead to kidney failure or even death.  E. coli can be divided into four main phylogenetic groups, A, B1, B2, and D.  These groups give a better characterization of understanding how commensal bacteria or commensal E. coli can become a harmful pathogen.  Each of these three organisms show how commensal organisms help illuminate human phylogenetics through their diversity.  Each one helps the body in a different way and a few have eventually over time been able to acquire pathogenic traits, such as E. coli.  The commensal organisms are organisms that be helpful to the body, breaking down food, fighting off disease, exposing radiation, immune system assistance, and few other things; but can also hurt the body by bringing pathogens, diseases and illnesses to the body.  This happens over time and usually only with environmental changes.

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