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Lecture 4: Normal human Dr Nisreen Jawad Kadhim  NORMAL HUMAN MICROBIOTA The normal microbiota denotes the population of microorganisms that inhabit the skin and mucous membranes of healthy normal persons. The normal microbiota provides a first lin...

Lecture 4: Normal human Dr Nisreen Jawad Kadhim  NORMAL HUMAN MICROBIOTA The normal microbiota denotes the population of microorganisms that inhabit the skin and mucous membranes of healthy normal persons. The normal microbiota provides a first line of defense against microbial pathogens, assists in digestion, and contributes to maturation of the immune system. Or the term used to describe the various bacteria and fungi that are permanent residents of certain body sites, especially the skin, oropharynx, colon, and vagina. The normal microbiota organisms are often referred to as commensals. Commensals are organisms that derive benefit from another host but do not damage that host.  The skin and mucous membranes always harbor a variety of microorganisms that can be arranged into two groups: (1) the resident microbiota consists of fixed types of microorganisms regularly found in a given area at a given age; if disturbed, it promptly reestablishes itself. (2) the transient microbiota consists of nonpathogenic or potentially pathogenic microorganisms that inhabit the skin or mucous membranes for hours, days, or weeks. The transient microbiota, does not produce disease, and does not establish itself permanently on the surface. The resident microbiota is disturbed, transient microorganisms may colonize, proliferate, and produce disease.  WHY ARE THESE MICROBES TEMPORARY?? 1. They may be washed from external areas by bathing. 2. They may not be able to compete with resident normal microbiota. 3. They may be killed by substances produced by the resident normal microbiota. 4. They may not survive in the acidic or alkaline pH of the site. 5. They may be flushed away by bodily secretions like tears, sweat, oil, urine, feces,..).  The members of the normal microbiota play a role both in the maintenance of health and in the causation of disease in three significant ways: (1) They can cause disease especially in immunocompromised and debilitated individuals. Although these organisms are nonpathogens in their usual anatomic location, they can be pathogens in other parts of the body. (2) They constitute a protective host defense mechanism. The nonpathogenic resident bacteria occupy attachment sites on the skin and mucosa that can interfere with colonization by pathogenic bacteria. The ability of members of the normal microbiota to limit the growth of pathogens is called colonization resistance. If the normal microbiota is suppressed, pathogens may grow and cause disease. For example, antibiotics can reduce the normal colonic microbiota that allows Clostridium difficile, which is resistant to the antibiotics, to overgrow and cause pseudomembranous colitis. (3) They may serve a nutritional function. The intestinal bacteria produce several B vitamins and vitamin K. Poorly nourished people who are treated with oral antibiotics can have vitamin deficiencies as a result of the reduction in the normal microbiota. 4- The normal flora may antagonize other bacteria through the production of substances which inhibit or kill non-indigenous species. Intestinal bacteria produce a variety of substances like non-specific fatty acids, peroxides and highly specific bacteriocins, which inhibit or kill other bacteria. 5- The normal flora stimulates the production of “cross-reactive antibodies’’. Since the normal flora behave as antigens, they induce an Ab mediated immune response. Low levels of antibodies produced against components of the normal flora are known to cross react with certain related pathogens, and thereby prevent infection or invasion.  WHERE CAN WE FIND NORMAL MICROBIOTA?  NORMAL MICROBIOTA OF THE SKIN The skin is the human body’s largest organ, colonized by microorganisms, most of which are harmless or even beneficial to the host. Skin can acquire any transient bacteria from the environment but it either get washed off or die because the skin is dry, has acidic pH, and produce sweat and oil. Resident bacteria of the skin can be in any layer of the skin. The predominant resident microorganisms of the skin are aerobic and anaerobic diphtheroid bacilli (eg, Corynebacterium, Propionibacterium) nonhemolytic aerobic and anaerobic staphylococci (Staphylococcus epidermidis)  gram positive, aerobic, spore-forming bacilli that are ubiquitous in air, water, and soil; - hemolytic streptococci (viridans streptococci) and enterococci (Enterococcus species); and gram-negative coliform bacilli and Acinetobacter. The predominant organism is Staphylococcus epidermidis, which is a nonpathogen on the skin but can cause disease when it reaches certain sites, such as artificial heart valves and prosthetic joints. Anaerobic organisms, such as Propionibacterium and Peptococcus, are situated in the deeper follicles in the dermis, where oxygen tension is low. Propionibacterium acnes is a common skin anaerobe that is implicated in the pathogenesis of acne.  NORMAL MICROBIOTA OF THE MOUTH AND UPPER RESPIRATORY TRACT A wide spectrum of organisms colonize the nose, throat, and mouth, but the lower bronchi and alveoli typically contain few, if any, organisms. The nose is colonized by a variety of streptococcal and staphylococcal species, the most significant of which is the pathogen S. aureus. The throat contains a mixture of viridans streptococci, Neisseria species, and S. epidermidis. These nonpathogens occupy attachment sites on the pharyngeal mucosa and inhibit the growth of the pathogens Streptococcus pyogenes, Neisseria meningitidis, and S. aureus, respectively.  Within 4–12 hours after birth, viridans streptococci become established as the most prominent members of the resident flora and remain so for life. These organisms probably originate in the respiratory tracts of the mother and attendants. Early in life, aerobic and anaerobic staphylococci, gram-negative diplococci (Neisseriae, Moraxella catarrhalis) and diphtheroids. When teeth begin to erupt, the anaerobic spirochetes, Prevotella species (especially Prevotella melaninogenica), Fusobacterium species establish themselves along with some lactobacilli. Actinomyces species are normally present in tonsillar tissue and on the gingivae in adults, and various protozoa may also be present. Yeasts (Candida species) occur in the mouth.  THE ROLE OF THE NORMAL MOUTH MICROBIOTA IN DENTAL PLAQUE AND CARIES In the mouth, Streptococcus mutans, a member of the viridans group, is of special interest since it is found in large numbers in dental plaque, the precursor of caries. The viridans streptococci, such as S. sanguinis, are also the leading cause of subacute bacterial (infective) endocarditis. These organisms can enter the bloodstream at the time of dental surgery and attach to damaged heart valves. Anaerobic bacteria, such as species of Bacteroides, Clostridium 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.  NORMAL MICROBIOTA OF THE INTESTINAL TRACT At birth, the intestine is sterile, but organisms are soon introduced with food. Many early studies reported that the intestinal microbiota of breast fed children is dominated by Bifidobacteria. However, recent studies suggested that in most babies, Bifidobacteria did not appear until several months after birth and thereafter persisted as a minority population. In bottle-fed children, a more mixed flora exists in the bowel, and lactobacilli are less prominent. As food habits develop toward the adult pattern, the bowel flora changes.  NORMAL MICROBIOTA OF THE CONJUNCTIVA The predominant organisms of the conjunctiva are diphtheroids, S epidermidis, and nonhemolytic streptococci. Neisseriae and gram-negative bacilli are also frequently present. Tears (Lysozyme enzyme) will protect the conjunctiva of the eye from colonization by more bacteria.  Stomach: Only few bacteria are present in the stomach due to gastric enzymes and acidic pH. Small intestine: Only few normal flora are present in the upper part of small intestine because bile kills them. Lower parts have more number of normal microbiota Large intestine: - Has more bacteria than any other part of the body. 99% of normal microbiota in the large intestine are anaerobic Bacteroides spp. - Many of the normal microbiota are opportunistic i.e. if they move to other areas - e.g. E.coli cause urinary infection.  The small intestine usually contains small numbers of streptococci, lactobacilli, and yeasts, particularly Candida albicans larger numbers of these organisms are found in the terminal ileum. The colon is the major location of bacteria in the body. the most important of which is Bacteroides fragilis. The most abundant facultative bacteria are the coliforms, of which Escherichia coli is the most important. The normal microbiota of the intestinal tract plays a significant role in extraintestinal disease. For example, E. coli is the leading cause of urinary tract infections, and B. fragilis is an important cause of peritonitis associated with perforation of the intestinal wall following trauma, appendicitis.  Urine in the bladder is sterile in the healthy person, but during passage through the outermost portions of the urethra, it often becomes contaminated with S. epidermidis, coliforms, diphtheroids, and nonhemolytic streptococci. The skin surrounding the genitourinary tract is the site of Staphylococcus saprophyticus, a cause of urinary tract infections in women. Q/Why do the normal flora not induce an immune response from the host? The short answer to this question is: the normal flora do induce an immune response. Antibodies to the normal flora exist in our bodies, but at lower concentrations than would exist for pathogenic bacteria. They provide a "sparring partner" for the human body that keeps the immune system in tune.