Normal human flora Dr.T.V.Rao MD Dr.T.V.Rao MD

Human microbiome The human microbiome (or human micro biota) is the aggregate of microorganisms that reside on the surface and in deep layers of skin, in the saliva and oral mucosa, in the conjunctiva, and in the gastrointestinal tracts. They include bacteria, fungi. Some of these organisms perform tasks that are useful for the human host. However, the majority have no known beneficial or harmful effect. Those that are expected to be present, and that under normal circumstances do not cause disease, but instead participate in maintaining health, are deemed members of the normal flora Dr.T.V.Rao MD

Normal bacterial Flora More bacterial than human cells in the body provide some nutrients (vitamin K) stimulate immune system, immunity can be cross-reactive against certain pathogens Prevent colonization by potential pathogens (antibiotic-associated colitis, Clostridium difficile) Dr.T.V.Rao MD

Overview of Human-Microbial Interactions Microbial flora of the healthy human host 1) The reasons for understanding the normal flora of the healthy human body ▶ Normal flora vs. human body ▶ Some normal flora:  opportunistic pathogens when injury occurred,                                             when resistance of body decreased,                                             when moved to another site 2) Origin of the normal flora 3) Relationship between normal flora and human host 4) Distribution and occurrence of the normal flora Dr.T.V.Rao MD

Where to find microbe? Everywhere! Dr.T.V.Rao MD

Introduction of Normal Flora A diverse microbial flora => Human body Area: the skin and mucous membranes Time: shortly after birth until death Number: 1014 bacteria =>1013 host cells 2. Normal flora may: a. Aid the host b. Harm the host (in sometimes) c. Exist as commensals (no effect to the host) Viruses and parasites => NOT normal microbial flora Most investigators consider that they are not commensals and do not aid the host. Dr.T.V.Rao MD

Normal Flora and Pathogenesis Outcomes of exposure to a microorganism: Transient colonization Permanent colonization Disease Colonization vs. Infection Colonization: establishment of a site of reproduction of microbes on a person without necessarily resulting in tissue invasion or damage. Infection: growth and multiplication of a microbe in or on the body of the host with or without the production of disease. Dr.T.V.Rao MD

Significance of Normal Flora 1.The normal flora influences the anatomy, physiology, susceptibility to pathogens, and morbidity of the host. 2. The effect of the normal flora on the host was not well understood until germ-free animals became available. Cesarean Section => Germ-free animals => Isolators w/o detectable pathogens (viruses, bacteria & others) 3. Two interesting observations: a. the germ-free animals lived almost twice as long as their conventionally maintained counterparts. b. the major causes of death were different in the two groups. Dr.T.V.Rao MD

Factors Influencing Normal Flora Local Environment (pH, temperature, redox potential, O2, H2O, and nutrient levels…). Diet Age Health condition (immune activity…) Antibiotics,…..etc Dr.T.V.Rao MD

Significance of Normal Flora Normal flora may aid the host in several ways: Aid in digestion of food Help the development of mucosa immunity Protect the host from colonization with pathogenic microbes. 106 pathogenic microbes GI infection w/ normal flora 10 pathogenic microbes GI infection w/ reduced flora after Streptomycin treatment Dr.T.V.Rao MD

Composition of the Normal Flora The normal flora of humans are exceedingly complex and consist of more than 200 species of bacteria. The makeup of the normal flora may be influenced by various factors, including genetics, age, sex, stress, nutrition and diet of the individual. Three developmental changes in humans, weaning, the eruption of the teeth, and the onset and cessation of ovarian functions, invariably affect the composition of the normal flora in the intestinal tract, the oral cavity, and the vagina, respectively. However, within the limits of these fluctuations, the bacterial flora of humans is sufficiently constant to a give general description of the situation Dr.T.V.Rao MD

Dr.T.V.Rao MD

When we get colonized with Normal Flora A human first becomes colonized by a normal flora at the moment of birth and passage through the birth canal. In utero, the fetus is sterile, but when the mother's water breaks and the birth process begins, so does colonization of the body surfaces. Handling and feeding of the infant after birth leads to establishment of a stable normal flora on the skin, oral cavity and intestinal tract in about 48 hours. Dr.T.V.Rao MD

A new born child's flora is dependent on mother The composition of a child’s bacterial flora is dependent on the mother’s micro flora, since she is the primary source for the child’s bacteria at the outset Dr.T.V.Rao MD

Density of normal flora in Humans It has been calculated that a human adult houses about 1012 bacteria on the skin, 1010 in the mouth, and 1014 in the gastrointestinal tract. The latter number is far in excess of the number of eukaryotic cells in all the tissues and organs which comprise a human. The predominant bacteria on the surfaces of the human body are listed in Table 3. Informal names identify the bacteria in this table. Dr.T.V.Rao MD

Normal Flora Resident flora Reflects sex of person Dr.T.V.Rao MD

Potential colonization sites Dr.T.V.Rao MD

Humans as Habitats Colonization (and infection) frequently begin at mucous membranes These are found throughout the body. Consist of single or multiple layers of epithelial cells, tightly packed cells in direct contact with the external _____________________________. Bacteria may associate loosely or firmly Breaches in the _______________ barrier can result in infection (pathogenesis)by opportunistic pathogens Dr.T.V.Rao MD

Upper respiratory tract – and Lower Respiratory tract Dr.T.V.Rao MD

Common Skin Bacterium May Be New Opportunistic Pathogen* Helococcus kunzii is a recently identified bacterium that is thought to be a nonpathogenic member of normal human skin flora and is rarely associated with skin infections. In the study though, the researchers report the isolation of the organism from an infected cyst on the breast of a 57-year-old immunocompromised woman. Finding provides further support for the opportunistic role of H. kunzii in causing infection in both immunosuppressed and immunocompetent patients," say the researchers. A.H. Chagla, A.A. Borczyk, R.R. Facklam, and M. Lovgren. 1998. Breast abscess associated with Helocococcus kunzii. Journal of Clinical Microbiology. 36:2377-2379.) Dr.T.V.Rao MD

Associations Between Humans and the Normal Flora E. coli is the best known bacterium that regularly associates itself with humans, being an invariable component of the human intestinal tract.  Even though E. coli is the most studied of all bacteria, and we know the exact location and sequence of 4,288 genes on its chromosome, we do not fully understand its ecological relationship with humans Dr.T.V.Rao MD

commensal relationship. Sometimes the relationship between a member of the normal flora an its host cannot be deciphered. Such a relationship where there is no apparent benefit or harm to either organism during their association is referred to as a commensal relationship. Many of the normal flora that are not predominant in their habitat, even though always present in low numbers, are thought of as commensal bacteria. However, if a presumed commensal relationship is studied in detail, parasitic or mutualistic characteristics often emerge. Dr.T.V.Rao MD

Normal flora are Mutualistic Much is not known about the nature of the associations between humans and their normal flora, but they are thought to be dynamic interactions rather than associations of mutual indifference.  Both host and bacteria are thought to derive benefit from each other, and the associations are, for the most part, mutualistic.  The normal flora derive from their host a steady supply of nutrients, a stable environment, and protection and transport. The host obtains from the normal flora certain nutritional and digestive benefits, stimulation of the development and activity of immune system, and protection against colonization and infection by pathogenic microbes. Dr.T.V.Rao MD

Normal Flora of the Gastrointestinal Tract (GIT) In bottle-fed infants Bifidobacteria are not predominant. When breast-fed infants are switched to a diet of cow's milk or solid food, bifidobacteria are progressively joined by: 1. Enterics 2. Bacteroides 3. Enterococci 4. Lactobacilli 5. Clostridia Dr.T.V.Rao MD

Normal Microbial Flora of the Gastrointestinal Tract Functions and Products of Intestinal Flora Intestinal microbes carry out a variety of essential metabolic reactions that produce various compounds The type and amount produced is influenced by the composition of the intestinal flora and the diet Compounds produced include vitamins B12 and K gas Dr.T.V.Rao MD

Dr.T.V.Rao MD

The flora of the large intestine (colon) 1. Enterococci 2. Clostridia 3. lactobacilli 4. Bacteroides 5. Bifidobacterium (Bifidobacterium bifidum) 6. Escherichia coli 7. Methanogenic bacteria 8. Viridans streptococci 9. Staphylococcus sp. 10. Proteus sp. 11. Candida albicans (Yeast) 12. Mycoplama sp. Dr.T.V.Rao MD

Normal Flora of the Respiratory Tract A) The nares (nostrils) 1. Staphylococcus epidermidis 2. Corynebacterium Staphylococcus aureus 4. Neisseria sp. 5. Haemophilus sp 6. Streptococcus pneumoniae Dr.T.V.Rao MD

Normal Flora of the Respiratory Tract B) The upper respiratory tract (nasopharynx). 1. Non-hemolytic streptococci 2. Alpha-hemolytic streptococci 3. Neisseria sp. 4. Streptococcus pneumoniae 5. Streptococcus pyogenes 6. Hemophilus influenzae 7. Neisseria meningitidis Dr.T.V.Rao MD

Normal Flora of the Respiratory Tract C) The lower respiratory tract (trachea, bronchi, and pulmonary tissues): Usually sterile. The individual may become susceptible to infection by pathogens descending from the nasopharynx e.g. H. influenzae S. pneumoniae). Dr.T.V.Rao MD

Normal Flora of the Human Oral Cavity Oral bacteria include: 1. Viridans streptococci 2. Lactobacilli 3. Staphylococci (S. aureus and S. epidermidis) 4. Corynebacterium sp. 5. Bacteroides sp. 6. Streptococcus sanguis (dental plaque) 7. Streptococcus mutans (dental plaque) 8. Actinomyces sp. Dr.T.V.Rao MD

Sites of human body that the normal flora microbes colonize Respiratory tract and head outer ear, eye, mouth, oropharynx, nasopharynx Sterile sites: sinuses, middle ear, brain, lower respiratory tract (trachea, bronchiole, lung) Gastrointestinal tract esophagus, stomach, small intestine, large intestine Genitourinary system anterior urethra, vagina Sterile sites: bladder, cervix, uterus Skin Dr.T.V.Rao MD

Normal flora may act as opportunistic pathogens Especially in hosts rendered susceptible by: 1. Immuno-suppression (AIDS & SCID) 2. Radiation therapy & Chemotherapy 3. Perforated mucous membranes 4. Rheumatic heart disease…etc. Dr.T.V.Rao MD

Normal Flora absent in … Sterile tissues In a healthy human, the internal tissues such as: blood brain muscle cerbrospinal fluid (csf.) are normally free of microorganisms. Dr.T.V.Rao MD

Importance of The Normal Flora (Advantages) 1. They constitute a protective host defense mechanism by occupying ecological niches. Dr.T.V.Rao MD

Normal Flora of the Skin The most important sites are: 1. Axilla 2. Groin 3. Areas between the toes Dr.T.V.Rao MD

Importance of The Normal Flora (Advantages) The oral flora contribute to immunity by inducing low levels of circulating and secretory antibodies that may cross react with pathogens. Dr.T.V.Rao MD

Importance of The Normal Flora (Disadvantages) 1. They can cause disease in the following: a) When individuals become immunocompromised or debilitated. b) When they change their usual anatomic location. Dr.T.V.Rao MD

Fecal bacteriotherapy Fecal bacteriotherapy, which is now officially and scientifically known as fecal micro biota transplantation and is also referred to as fecal micro biota therapy, fecal transfusion, fecal transplant, stool transplant, fecal enema or human probiotic infusion (HPI), is a medical treatment for patients with pseudomembranous colitis (caused by Clostridium difficile), or ulcerative colitis that involves restoration of colon homeostasis by reintroducing normal bacterial flora from stool obtained from a healthy donor. Dr.T.V.Rao MD

Fecal micro biota transplantation Fecal micro biota transplantation (FMT) -- also known as fecal bacteriotherapy, among other names -- is an effort to calm a troubled bowel by reintroducing the vast diversity of collaborative bowel inhabitants after the usual mix has been disturbed. More than 1,000 different strains of bacteria co- exist peacefully in the typical healthy bowel. But when the delicate balance is altered, by antibiotics or other causes, a few strains can become dominant, leading to severe diarrhea, inflammation and tissue damage. Dr.T.V.Rao MD

microbiota transplantation Like an organ transplant, fecal microbiota transplantation begins with finding a donor, often a family member. The treatment team collects a fresh stool sample, at least 200 to 300 grams. The sample is mixed with salt water in a blender and filtered to remove particulate matter. It can be administered to the recipient through a colonoscopy, as an enema, or -- when the inflamed region is higher in the colon -- through a naso-gastric tube. Dr.T.V.Rao MD

Programme created by Dr. T. V Programme created by Dr.T.V.Rao MD for Medical and Paramedical students in the Developing World Email doctortvrao@gmail.com Dr.T.V.Rao MD