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Role of Human Microflora 1 & 11

Dr. Patrick E. Akpaka OPTOM 1012 Lecture Notes 2011 -2012 Academic Year

Definitions: Normal (indigenous) microflora, normal body flora and normal biota are different terms used to describe the various microbial species which normally inhabit the skin, mucous membranes and other non-sterile sites on the animal without causing disease. Resident microflora: those organisms that are always present on the body. Transient microflora: those present temporarily and under certain conditions. There are different relationships that microbes can share with the animal: Commensalism: one organism benefits, the other is unaffected (microbes on your skin). Mutualism: both organisms benefit (E. coli makes vitamin K for humans). Parasitism: one organism benefits at the other organisms expense. Normal body flora may consist of more than 200 species of bacteria. A body site can harbour normal flora or it can be sterile (harbouring no flora), please take the opportunity to fill in: Site Liver Skin Mucous membranes Lungs Colon Blood Middle and inner ear Brain CSF Bones Vagina Heart Amniotic fluid
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Harbours normal flora

Sterile

Distal urethra Urinary bladder Muscle External ear The composition of normal body flora depends on factors such as: genetics, age, sex, stress, geographic location, climate, nutrition and diet of an individual. It may be influenced by other factors such as drug therapy and hormonal changes. Normal body flora tends to be host (tissue) adapted which may be referred to as tissue tropism. This may be due to the fact that at a particular site, the host provides essential nutrients needed by the bacterium. However at other sites the bacterium will not thrive because of an inhospitable environment for the bacterium by the production of such substances as stomach acids, bile salts and lysozyme. Many of the normal flora are able to specifically colonize a particular tissue or surface using their own surface components like capsules, fimbriae and cell wall components as specific ligands for attachment to specific receptors located at the colonization site. Some of the indigenous bacteria are able to construct bacterial biofilms on a tissue surface, or they are able to colonize a biofilm built by another bacterial species. Many biofilms are a mixture of microbe s, although one member is responsible for maintaining the biofilm and may predominate. One example of a biofilm is dental plaque on the teet.h

Sites of Normal biota

The Skin Contains microbes located mainly in the most superficial layers of the epidermis and upper portions of hair follicles. The skin biota present in the skin are mainly Staphylococcus spp., Micrococcus spp., diphtheroids such as Propionibacterium acnes and fungi such as Candida sp. Staphylococcus spp. include the potentially pathogen Staphylococcus aureus and the opportunist Staphylococcus epidermidis. Diptheroids such as Propionibacterium sp. including the anaerobes Propionibacterium acnes, which can cause acne. These bacteria are generally commensals, however if the normal conditions change so to can the relationship. Staphylococcus spp. and Proprionibacteria sp. can produce fatty acids that inhibit the growth of fungi and yeast in the skin. Fungi on the skin include yeasts belonging to the genus Pityrosporum, which use fats as a substrate for growth and grow on oily areas on the face, scalp, chest, and back.
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The mite Demodex spp. lives on the face, within hair follicles and in the openings to oil glands in humans and dogs. The Conjunctivae The conjunctivae are defended by the continuous secretions of the lachrymal glands which keeps the conjunctiva moist and contain bacteriocidal substances such as lysozyme, blinking also helps to physically move foreign objects away such as bacteria. Only microorganisms with special mechanisms capable of attaching to epithelial surfaces and withstanding the lysozyme attack would be able to colonize the conjunctiva. Some pathogens capable of infecting the conjunctiva include Neisseria gonorrhoeae and Chlamydia trachomatis, it is thought that these organisms attach to the conjunctival epithelium. Staphylococcus epidermidis and certain other coryneforms such as Proprionibacterium acnes are predominant. Other organisms occassionaly found on the conjunctiva include Staphylococcus aureus, some Streptococci sp., Haemophilus sp. and Neisseria sp. Newborn infants may be especially prone to bacterial attachment. Since Chlamydia sp. and Neisseria sp. can be present on the cervical and vaginal epithelium of an infected mother, silver nitrate or an antibiotic may be put into the newborn's eyes to avoid infection after passage through the birth canal. The Respiratory Tract (Upper and Lower Respiratory Tract) The microbiota of the nasal cavity and nasopharynx are particularly well adapted to adhere because of the mucociliary system. The Upper Respiratory Tract The upper respiratory tract is colonized by numerous species of bacteria. The nostrils/nares are heavily colonized by Staphylococcus epidermidis, Corynebacterium spp. and in about 20% of the population Staphylococcus aureus may be found here. The nares being the main carrier site for this organism. The pharynx (throat) is colonized by Streptococci sp. and various Gram-negative cocci. Pathogenic bacteria that may sometimes colonize the pharynx include Streptococcus pneumonaie, Streptococcus pyogenes, Haemophilus influenza and Neisseria meningitides. It must be noted that healthy sinuses are considered sterile. With respect to animals the bacteria present are similar to those seen in humans, these include: Micrococcus spp., Staphylococcus sp., Streptococcus sp., Bacillus sp. Lactobacillus sp. Actinomyces sp. spirochetes, mycoplasmas, Pasturella sp. Diphtheriods, pneumococci, yeasts such as Candida albicans and Haemophilus sp.
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The Lower Respiratory Tract (trachea, bronchi and pulmonary tissue). The lower respiratory tract is considered virtually free of microorganisms due to the presence of ciliated epithelium that lines the tract. Bacteria that reach the lower respiratory tract are swept upwards by the action of the mucocilliary blanket that lines the bronchi, from here, coughing, sneezing or swallowing will remove the bacteria. At times the epithelial lining may become damaged such as in bronchitis and viral pneumonia. This causes the individual to become more susceptible to pathogenic bacteria such as Haemophilus influenza and Streptococcus pneumoniae which enter through the nasopharynx. The Oral Cavity The mouth is a warm, moist environment with abundant nutrients, epithelial debris and secretions which make the mouth a favourable habitat for numerous bacteria. Bacteria present in the oral cavity include Streptococcus spp. (haemolytic and non-haemolytic), Lactobacillus sp., Staphylococcus spp. and diphtheriods as well as some anaerobes such as Bacteroides spp. As a person ages the ecological situation in the oral cavity changes and so too does the normal flora. At birth, the composition of the oral cavity is solely soft tissue such as lips, cheeks, tongue and palate which are kept moist by the salivary glands. At birth the oral cavity is sterile but at the first feeding by the mother the oral cavity becomes rapidly colonized by organisms from the environment. Streptococcus mutans, can cause tooth decay as these bacteria require a non-desquaminating (nonepithelial) surface in order to colonize the mouth. The other strains of streptococci. adhere to the gums and cheeks but not to the teeth. There is no doubt that the normal biota of the oral cavity benefit from the nutrients and habitat provided by the host. However there are also benefits to the host as well, this includes the fact that normal flora occupy colonization sites making it difficult for nonindigenous species to become established. In addition oral flora can synthesize vitamins and contribute to immunity as they can induce low levels of circulating and secretory antibodies that may cross react with pathogens. The normal flora of the mouth can also exert microbial antagonism against the nonindigenous species by production of inhibitory substances such as fatty acids, peroxides and bacteriocins. It must be noted at this point that normal flora can cause various oral diseases in humans, including abscesses, dental caries, gingivitis and periodontal disease. Oral bacteria can also cause abscesses in the alveolar bone, lung, brain or extremities. Infections such as these can contain a mixture of bacteria inclusive of Bacteriodes melanogenicus. It must also be noted that Streptococcus spp. from the mouth can be introduced into wounds created by dental
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manipulation or treatment, these organisms can cause subacute bacterial endocarditis by adhering to the heart valves. The Intestinal Tract The bacterial flora of the gastrointestinal tract of various species of animals has been studied more extensively than any other site. The normal flora of the gastrointestinal tract varies between the animal species as well as within species. The esophagus, stomach, and upper intestine are too inhospitable to sustain a normal biota and hence contains only the bacteria swallowed with saliva and food. Due to the high acidity of gastric juice, there are very few bacteria which can be cultured from the normal stomach of a human, mainly acid-tolerant lactobacilli can be observed. However studies have shown that at least half of the American population is colonized by Helicobacter pylori which is pathogenic. This bacterium is known to cause gastric ulcers and possibly even gastric and duodenal cancer. In the lower intestine, intestinal movement is less vigorous. A complex microbial community develops there. The first intestinal tract evacuations in a newborn are germ-free but that quickly changes on the first feeding. The small intestine contains sparse amounts of Gram-positive flora consisting mainly of Lactobacillus spp. and Enterococcus faecalis. As one moves from proximal to the distal part of the small intestine the numbers of bacteria increase, in addition to the number of species. Coliforms such as E. coli and relatives as well as Bacteroides spp. join the list of organisms that can be found. The quality of flora found in the large intestine is similar to that found in the faeces. The majority of species in the lower intestine are strict anaerobes belonging to the genera Bacillus, Bacteroides, Bifidobacterium, and Clostridium (Clostridium perfringens and Clostridium septicum). Facultative anaerobes include the Enterobacteriaceae (such as Escherichia coli, Klebsiella sp., Enterobacter sp., Pseudomonas sp., Proteus spp.) and Lactobacillus spp. The intestinal flora is important because it is in here that we can see the most profound effect of the bacterial flora on their host. This may be due to their large numbers and mass. In humans the microbiota of the GI tract have been demonstrated to be producers of vitamins and may contribute to nutrition and digestion. The most important effects of the normal biota are their ability to protect their host from the establishment of infection by foreign microbes and also their ability to stimulate the development and the activity of the immunological tissues. However some bacteria present in the colon such as Bacteroides spp. have been shown to produce metabolites that are carcinogenic, it is possible that there may be an increase in the incidence of colon cancer associated with these bacteria. It is important to note that changes in the gastrointestinal flora are brought about by poor nutrition and antimicrobial therapy, these can lead to shifts in the populations and colonization by non-residents thus leading to disease.
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The Urogenital Tract The urine is normally sterile, in fact the urinary tract is flushed every few hours. Due to this fact microorganisms have problems gaining access and becoming established. The Urethra Only the outermost part of the urethra, where the mucous membranes meet the skin, supports a microbiota. Usually, relatively low numbers of enterococci (such as Enterococcus faecalis), Staphylococcus epidermidis and some alpha-haemolytic Streptococcus spp. are present on the outer part of the urethra. Contaminants from the skin, vulva and rectum may occassionally be found in this area and include enteric bacteria such as E. Coli and Proteus sp., and Corynebacterium sp. The Vagina The vagina is a warm, moist, protected environment, the colonization of the vagina begins soon after birth. Common inhabitants include Corynebacterium sp., Staphylococcus sp., Streptococcus sp. E. coli and Lactobacillus spp. When influenced by estrogen the vagina epithelium contains glycogen, it becomes acidic with the growth of lactobacilli which metabolize the glycogen to lactic acid. The production of this lactic acid and other products inhibit colonization by most bacteria except the lactobacilli and a select number of lactic acid bacteria. The acidic pH generated also prevents the growth of potentially-pathogenic yeast such as Candida albicans. When estrogen is not being produced, it is alkaline and more prone to infections.

Site Skin

Eye Teeth and oral cavity

Stomach Reproductive system

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Organism (Genera) Staphylococcus Proprionibacteria Diptheriods* Candida Staphylococcus Streptococcus Neisseria Streptococcus Bacteriodes Fusobacterium Lactobacillus Lactobacillus Candida Staphylococcus

Upper respiratory tract

Tongue

Small intestine

Large intestine

Streptococcus Neisseria E. coli Candida Staphylococcus Streptococcus Neisseria Haemophilus Branhamella Candida Streptococcus Neisseria Lactobacillus Enterococcus Lactobacillus Bacteroides E. coli E. coli Proteus Klebsiella Enterobacter Bacteriodes

*group name

Is Normal Biota helpful or harmful? The benefits of normal biota probably outweigh possible harmful effects. The most significant beneficial effect of microbiota derives from microbial antagonism. Microbiota also stimulates our immune system in a nonspecific way. Some intestinal bacteria provide supplemental sources of vitamin K and B12. If our relationship with microorganisms is altered, pathogens can established themselves in underpopulated areas or normally harmless commensals can proliferate and cause opportunistic infections. Categorizing microorganisms as harmful or harmless is not always clear-cut. The hosts state of health often determines whether diseases occur. Microorganisms exist along a continuous spectrum of disease-causing potential. Today, because of advanced medical technology, more people die from infection by opportunists than by true pathogens. Beneficial Effects of Normal Flora 1. The synthesis and excretion of vitamins. In humans enteric bacteria secret Vitamin K and Vitamin B12, while lactic acid bacteria produce certain B-vitamins.

2. The prevention of colonization by other pathogens. Normal flora can prevent colonization by pathogens by competing with the pathogens for attachment sites or essential nutrients as demonstrated in the oral cavity, the intestine, skin and vaginal epithelium.

3. Normal flora can antagonize other bacteria. This can occur through the production of substances which inhibit or kill nonindiginous species. For example intestinal flora can produce substances ranging from relatively non specific fatty acids and peroxides to highly specific bacteriocins which inhibit or kill other bacteria.

4. Normal flora can stimulate the development of certain tissues.

For example the caecum and some lymphatic tissue such as Peyers patches. It is noted that the caecum of germ-free animals is enlarged, thin-walled and fluid filled when compared to that of conventional animals.

5. The stimulation of the production of natural antibodies. Due to the fact that normal flora can behave as antigens in animals they can induce and immunological response. Low levels of antibodies produced against the components of normal flora can cross react with some other related pathogens, thereby preventing infection or invasion.

The harmful effects of normal flora are as follows: 1. Bacterial synergism That is one organism can help the other one grow and survive. Examples of this occurs when normal flora supply vitamins and other growth factors for pathogenic bacteria to grow. Another example is cross-feeding. This occurs between microbes such as in staphprotected infections when a penicillin-resistant staphylococcus (a component of normal flora) shares its drug resistance with other pathogens.

2. Competition for nutrients. The bacteria may absorb some of the nutrients the host needs, this can be demonstrated by the fact that germ-free animals grow more rapidly and efficiently than normal animals. This is the reason why animals are given antibiotics in their food. However this practice may lead to the development of antimicrobial resistance.

3. The induction of a low grade toxaemia. Minute amounts of bacterial toxins enter the systemic circulation.

4. Normal flora may be agents of disease.

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Members of normal flora can cause endogenous disease if they enter restricted sites or sites where they are not tolerated by the hosts defences. Many normal flora are potential pathogens. They gain access to compromised tissue from which they can invade.

5. Transfer to susceptible hosts. Some pathogens such as those colonizing the upper respiratory tract can produce disease, these include Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus, and potential pathogens such as E. coli, Salmonella spp. or Clostridium spp. in the gastrointestinal tract.

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