1. Microbiota (Normal Flora)
Basic Bacteriology
Part-4
First Semester

2. Definitions:
Symbiosis: refers to a close and prolonged interaction between organisms of different species.
Each of the organisms that is involved in symbiosis is called symbiont.
The symbiotic relation could be:
Mutualism: refers to a symbiotic relationship with mutual benefits
Commensalism: refers to a symbiotic relationship during which one of the symbiont benefits but the other is not harmed
Parasitism: refers to a symbiotic relationship during which one of the symbiont benefits and the other is harmed.
Host: refers to a larger symbiont that can support the survival and growth of a smaller symbiont.

3. Microbiota:
Microbiota is a term that is used to describe microorganisms that live in a symbiotic relationship with living multi-cellular organisms (lager symbiont (host)) at certain anatomical location (s).
The association of some of these microorganisms is permanent. Thus they are called as permanent residents. On the other hand, some of these microorganisms are associated transiently with their host.
Human microbiota includes bacteria, archaea and fungi that can be found at certain anatomical locations of the human body.
Human microbiota includes hundreds, if not thousands of bacterial species. However, the only fungal species that may be found among human microbiota is, Candida albicans, which can be found in mouth, large intestine, vagina and on skin.
Human body harbors billions and billions of bacteria at certain anatomical locations such as:
1- Skin
2- Oral cavity
3- Upper Respiratory tract (nasal cavities, though, upper part of the trachea)
4- Colon (large intestine)
5- The last parts of the Urogenital tact (urethra, vagina)
It is estimated that the number of bacterial cells that each human harbors is about 10 times more than the t number of cells that build up the human body.

5. During intra-uterine, the fetus lives in a completely sterile environment. Thus, human babies are supposed to be born completely sterile.
However, during birth, the skin of the newborn may become colonized with some members of the viginal microbiota as well as the members microbiota that are found on skin of the medical staff and other persons that handle the baby after that including the mother.
Once the baby start being fed the intestinal tract (large intestine) become gradually colonized by different nonpathogenic bacterial species that can be found in the nutrients taken by the baby or found on the mothers nibbles .
Although humans have more or less similar members of bacterial microbiota, human microbiota can affected by several factors such as:
1- Age: physiological changes associated with human age affect microbiota
2- food habits of individuals or communities
3- Antibiotics
4- The status of the immune system, which can be affected by genetic mutations that affect the immune system, age, AIDS, cancer, chemotherapy, diabetes, immunosuppressive drugs…

6. The symbiotic relationship between humans and their microbiota can be considered as mutualism and commensalism. However, some members of human microbiota can be opportunistic pathogens.

7. Advantages:
1- Development of the immune system (experiments have shown that germ-free mice ( also known as Axenic /Gnotobiotic mice) develop a poor immune system
2- Production of certain vitamins (vitamins B and K)
3- Interfere with colonization of primary pathogens
Disadvantages:
Some members of the human microbiota can cause disease in certain cases:
1- Weakening or collapse of the immune system
2- Translocation into a sterile body site that are not supposed be at (such as balder, kidneys, blood stream, lungs, peritoneal cavity, CNS, muscle tissue)
3- Overgrowth of some members of normal flora during antibiotic administration ( sensitive members of normal flora die while resistant members overgrow)
Note: members of microbiota that can cause disease are known as opportunistic pathogens (secondary pathogens).
Note: oral normal flora play an important role in dental caries (Germ-free mice DO NOT develop dental caries)

8. The immune system keeps normal flora in check:
Although our immune system allows normal flora to inhabit certain body locations , it keeps normal flora in check:
Examples:
Skin produces many inhibitory substances that limit bacterial growth such as sweat and certain fatty acids
Lysosome that kills bacteria by (by destroying peptidoglycan) is secreted in saliva and tears
The mucosa of digestive tract secrete antibodies (IgA) and antibiotic peptides that limit bacterial growth

9. Examples of human Microbiota (memorize the underlined ones only)
A- Skin Normal Flora:
Staphylococcus epidermidis : it can cause disease when reaches certain sites such as artificial heart valves and prosthetic joints, where it can forms biofilms. (There are about 103–104 organisms/cm2 of skin).
Propionibacterium acnes: it is anaerobic bacterium that is found the deeper follicles in the dermis where oxygen tension is low. Propionibacterium acnes is implicated in the pathogenesis of acne.
Candida albicans (yeast): it is the only fungal member of the human normal flora that may be found on skin, in oral cavity and colon.
In healthy individuals, it may cause skin infections and vaginitis (because of over growth)
In immunocompromised patients, it may enters bloodstream when needles pierce the skin to cause life-threatening blood stream (candidemia) and systemic infections in immunocompromised patients.

10. B- Normal flora of the oral cavity:
1- Viridans streptococci make up about half of the normal flora of the oral cavity such as:
a-Streptococcus mutans, which is involved in dental caries
b-Certain species of viridans streptococci are considered as a leading cause of subacute bacterial endocarditis. These organisms can enter the bloodstream at the time of dental surgery and attach to damaged heart valves.
2- Eikenella corrodens, also part of the normal oral flora, causes skin and soft tissue infections associated with deep human bites.
3- Anaerobic bacteria, such as Bacteroides and Prevotella , which are found in the gingival crevices, where the oxygen concentration is very low. If aspirated, these organisms can cause lung abscesses, especially in debilitated patients with poor dental hygiene.
4-Porphyromonas gingivalis , causes peiodentitis that may result in the loss of teeth

11. C- Normal Flora of the Upper Respiratory Tract:
A wide spectrum of bacteria colonize the nose and the throat (upper part of the respiratory tract).
Note: lower bronchi, bronchioles and alveoli, contain few, if any, organisms.
1- The nose is colonized by a variety of Streptococcal and Staphylococcal species. The most significant of which is Staphylococcus aureus (colonize 30-50% of people).
From the nasal cavity, S. aureus may spread to colonize other anatomical locations such as skin, throat and vagina. S. aureus is an important opportunistic pathogen that can cause a wide range of infections, some of which can be life-threatening (examples wound infections, septicemia , septic shock, meningitis, osteomyelitis, pneumonia and UTI).
2-The throat contains a mixture of nonpathogenic viridans Streptococci, Neisseria species, Staphylococcus epidermides. They play an important role in inhibiting colonization of certain important pathogens such as Streptococcus pyogenes and Neisseria meningitide..
3- Streptococcus pneumoniae: it is found in about 40-50% of human. It can be an important opportunistic pathogen that can cause, otitis media, sinusitis, lung infection and meningitis

12. D- Normal Flora of the Intestinal Tract:
In normal healthy people, the stomach contains few organisms primarily because of its low pH, which kills most bacteria ingested with food.
The small intestine usually contains small numbers of Streptococci, Lactobacilli, and and Candida albicans.
The colon is a major location of normal flora in the body.
It is estimated that 1 gram of feces contains as many as 1011 bacteria.
More than 90% of the fecal microbiota are anaerobes, most important of which belong to the genus Bacteroides .
The most abundant facultative anaerobic bacteria belong to family Enterobacteriaceae, such as Escherichia coli, Proteus, Klebsiella, which are common opportunistic pathogens.
E. coli: is the leading cause of urinary tract infection.
Bacteroides fragilis: is an important cause of peritonitis associated with perforation of the intestinal wall that is associated with trauma and appendicitis.
Enterococcus faecalis: is an important cause urinary tract infections and endocarditis.

13. E- Normal flora of the urogenital tract (lower part):
Kidneys, ureters, and bladder are usually sterile and harbor almost no normal flora
Some skin microbiota can be found in the last pat of urethra.
In adult females, the vagina harbors Lactobacilli, which plays an important role in preventing or interfering with fungal infection.
Adult females that take certain types of antibiotic, may suffer from vaginal fungal infection as these antibiotics suppress vaginal microbiota allowing the fungi to colonize and cause infection (Candida albicans).
Some of the colon normal flora may also be found in the vagina (because of the short anatomical distance between anus and vagina in females). That why UTIs are more often seen in females than males.. Some of these may also cause bacterial vaginitis.

15. Inflammatory bowel diseases (IBDs) reflect the cooperative influence of numerous host and environmental factors, including those of elements of the intestinal immune system, the gut microbiota, and dietary habits. This review focuses on features of the gut microbiota and mucosal immune system that are important in the development and control of IBDs.
Gut innate-type immune cells, including dendritic cells, innate lymphoid cells, and mast cells, educate acquired-type immune cells and intestinal epithelial cells to achieve a symbiotic relationship with commensal bacteria. However, perturbation of the number or type of commensal microorganisms and endogenous genetic polymorphisms that affect immune responses and epithelial barrier system can ultimately lead to IBDs.
Providing beneficial bacteria or fecal microbiota transplants helps to reestablish the intestinal environment, maintain its homeostasis, and ameliorate IBDs.
The gut immune system participates in a symbiotic milieu that includes cohabiting commensal bacteria. However, dysbiotic conditions and aberrations in the epithelial barrier and gut immune system can disrupt the mutualistic relationship between the host and gut microbiota, leading to IBDs. Progress in our molecular and cellular understanding of this relationship has yielded numerous insights regarding clinical applications for the treatment of IBDs.

16. Beyond gut microbiota: understanding obesity and type 2 diabetes
HORMONES 2015, 14(3):
Beyond gut microbiota: understanding obesity and type 2 diabetes
Obesity and type 2 diabetes are metabolic diseases that have reached epidemic proportions worldwide. Although their etiology is complex, both result from interplay between behavior, environment and genetic factors. Within ambient determinants, human overall gut bacteria have been identified as a crucial mediator of obesity and its consequences.
Gut microbiota plays a crucial role in gastro-intestinal mucosa permeability and regulates the fermentation and absorption of dietary polysaccharides, which may explain its importance in the regulation of fat accumulation and the resultant development of obesity-related diseases.
The main objective of this review is to address the pathogenic association between gut microbiota and obesity and to explore related innovative therapeutic targets. New insights into the role of the small bowel and gut microbiota in diabetes and obesity may make possible the development of integrated strategies to prevent and treat these metabolic disorders.