aAK l 5 4 Normal microbiota and _ host-parasite relationship MBBS Year 1 Dr.Komathi Selly,= Explain the role of human microbiome and the relationship with disease and opportunities for ™ Describe the factors that affect and determine the normal flora explain the terms commensalism, mutualism, and parasitism. state the common microbiota residing at different si of human body. ™ describe the effects of broad-spectrum antibiotics@mthe normal microbiota. state the beneficial and the harmful effects ofthe normal microbiota.Normal microbiota The term "normal microbiota or normal flora" denotes the population of microorganisms that are normally present at specific sites of the body without causing any disease to healthy person. Two groups of microorganism: 1) Resident microbiota 2) Transient microbiota Conjunctiva —> Large —_ intestineResident microbiota The “Resident microbiota” consists of relatively fixed types of microorganisms regularly found in a given area at a given age; if disturbed, it rapidly reestablishes itself. Location : Skin, conjunctiva, mouth, nose, throat, large intestine, lower urethra and reproductive systems, especially near their openingsTransient microbiota Transient microbiota are microorganisms that can be present under certain conditions in any of the locations where resident microbiota are found. They are nonpathogenic or potentially pathogenic microorganisms. that inhabit the skin or mucous membranes for hours to months which does not produce disease. Example: An immunized person come in contact with a child infected with measles. Immunity will prevent the viruses from invading cells. But the person harbor the viruses as transmits for a short time. However, if the resident flora is disturbed, transient microorganisms may colonize, proliferate and produce disease.Role of microbiota in health parasitism | uniaterat benefit | \ | } harm >. benefit ‘mutuatism | reciprocal benefit none \ tah symbiosis 7 partial — > complete dependency There are at least 3 types of relationships based on the quali the relationship for each member of the symbiotic associal Mutualism Commensalism P;» Mutualism: » It is defined as the relationship in which each organism in interaction gets benefits from association. It is an obligatory relationship in which mutualist and host are metabolically dependent on each other. Q One classic mutualistic association is that of the the lactic acid bacteria that live on the vaginal epithelium of a woman. Q The bacteria are provided habitat with a constant temperature and supply of nutrients (glycogen) in exchange for the production of lactic acid, which protects the vagina from colonization and disease caused by yeast and other potentially harmful microbes. ~ actin iil ram-stained photomicrograph of a vaginal specimen, revealed the presence of uamous epithelial cells, and numerous (Gardneretta vaginalis Gram-positive bacilli, or rod shaped curved bacilli (Mot hacteria epithelial cell coated wittCommensalism: It is a relationship in which one organism (commensal) in the association is benefited while other organism (host) of the association is neither benefited nor harmed eters asast ators Wound roi ‘paired tumor romth Q Staphylococcus epidermidis, a consistent inhabitant of the skin of humans.The bacterium produces lactic acid that protects the skin from colonization by harmful microbes that are less acid tolerant. Q But it has been suggested that other metabolites that are produced by the bacteria are an important cause of body odors (good or bad, depending on your personal point of view) and possibly associated with certain skin cancers+ A parasite that causes disease in its host is called a pathogen. * Some parasitic bacteria live as normal flora of humans while waiting for an opportunity to cause disease. * Other nonindigenous parasites generally always cause disease if they associate with a nonimmune host. * It is a relationship in which one population (parasite) get benefited and derive its nutrition from other population (host) in the association which is harmed. * Viruses: * Viruses are obligate intracellular parasite that exhibit great host specificity.Alterations of the microbiome can aggravate the di restoration of the microbiome should be beneficial BACKGROUND SIGNS & SYMPTOMS. + MALANCE f MCRORAL SPECIES DUE Ts REDUCTION MERORIAL DIVERSITY Microbiome Perturbation Associates with “omgmurmmens “Ch Disease sous ley causes erie ssrmaes — ‘hemos umes ss ase “roeeme ste oun se Teenent “Sl cacora |+ DIETARY CHANGES ee ‘Mowene mates =n” aes | UFESTYLE MODIFICATIONS Teemessen | IS =e = Uy pee Eom oaThe gut microbiome appears altered in many chronic diseases 00 Crohn's ‘isoase Multiple 200: tp : Incidence of Immune Disorders (%) = = = 00. f 1950 1960 1970 1980 1990 2000 Seven of the top 10 causes of death in 2010 were chronic diseases. Two of these—heart disease and cancer—accounted for nearly 48% of deaths in the US centers for Disease Control and Prevention, 2013= Normal microbiota __ refers to the microorganisms that reside on the surface and deep layers of skin, in the saliva and oral mucosa, in the conjunctiva, and in the gastrointestinal tracts of every human being. ™ They have developed a symbiotic relationships with the host. ™ The normal flora is acquired at birth. ™ Our normal microbiota consists of various bacteria, fungi, and archaeaIR STOSeEAT CONSULT scalp as skin teeth |Streptococcus mutans Bacteroides Fusobacterium streptococci actinomyces: throat Strep. viridans ‘Strep. pyogenes Strep. pneumoniae ‘Novsseria spp. ‘Staphylococcus ‘epidermidis Haemophilus influenzae skin Staph. epidermidis Staph. aureus diphtheroids streptococci Pseudomonas ‘aeruginosa anaerobes, Candida Torulopsis Staph. aureus Staph. epidermidis diphtheroids streptococci ‘mouth Strep. mits and ‘other streptococe! Trichomonas tenax Candkido ung | 2 Pneumocystis jrovect ‘urethra and vagina Staphylococcus ‘epidormds diphtheroids | streptococe! Gram-negative rods ‘groin and perineum as skin feet Large intostine Bacteroides agit Eschorchia col Proteus mirabiis ‘obsiola species Lactobacitus species Streptococcus species Candida abcane Clostrctum species Pseudomonas species Enterococcus species* mucus production + antimicrobial chemicals * assist digestion + ward off pathogens * lubricate pulmonary tissues * prevents gastric complications + digestion of complex carbohydrates + maintain pH and Hz0, production to kill microbes * fortify immune system * scent productionFactors that affect the normal microbiota Their flourishing in a given area depends upon many physiologic factors : = Temperature: highly constant temperature (warm- blood animals). = Moisture = Presence of certain nutrients: rich in organic nutrients and growth factors = Inhibitory substances = Relatively constant conditions of pH and osmotic pressureSS Factors that Influence Gut Bacteri Composition ™ Method of delivery at birth = Infant feeding ™ Genetics ® Infections = Medications = Diet————ESE “NT. Modulation of central nervous system 1. Protection against pathogens 6. SCFA production by fermentation of dietary fiber <> 2. Synthesis of vitamins (2 5. Promotion "e fat storage 3. Immune system development ~~ Ge 4. Promotion of intestinal angiogenesis© Insulin resistance, 2 diabetes pe. ‘an Type 1 siabetes| © Metavotic syndrome ‘and obesityi Useful effects of the normal microbial biota on the human body The normal flora ea { Very imp in ¢ immunity . oe we're not ALL BAD!ee Useful as well as the harmful effects of the normal microbial biota on the human body = The resident flora of certain areas plays a definite role in maintaining health and normal function. = Members of the resident flora in the intestinal tract synthesize vitamin K and aid in the absorption of nutrients. ™ On mucous membranes and skin, the resident flora may prevent colonization by pathogens and possible disease through “bacterial interference”.= It may involve competition for receptors or binding sites on host cells, competition for nutrients, mutual inhibition by metabolic or toxic products, mutual inhibition by antibiotic materials or other mechanisms. = Suppression of the normal flora -organisms from the environment or from other parts of the body-behave as opportunists and may become pathogens. = Members of the normal flora may themselves produce disease under certain circumstances.= These organisms are adapted to the noninvasive mode of life defined by the limitations of the environment. = If forcefully removed from the restrictions of that environment and introduced into the bloodstream or tissues, these organisms may become pathogenic. = For example, streptococci of the viridans group are the most common resident organisms of the upper respiratory tract.= If large numbers of them are introduced into the bloodstream (e.g., following tooth extraction or tonsillectomy), they may settle on deformed or prosthetic heart valves and produce infective endocarditis. = Small numbers occur transiently in the bloodstream with minor trauma (e.g., dental scaling or vigorous brushing).Bacteroides are the commones *tesident bacteria of the large intestine and are quite harmless in that location. * If introduced into the free peritoneal cavity or into pelvic tissues along with other bacteria as a result of trauma, they cause bacteremia.Wyse — ae * Candida lives throughout our bodies in small amounts: in our oral cavity, digestive tract, gut microbiome, and vaginal tract. Its job is to aid with digestion and nutrient absorption—which it does when it’s in balance with the good bacteria in our microbiome. ® The problem occurs when there is too much Candida in relation to our body’s good bacteria, and it overpowers the bacteria, which can lead to a lot of digestive issues, as well as fungal infections, mood swings, and other psychological issues.SS Normal flora of the vagina ™ Soon after birth, aerobic lactobacilli appear in the vagina and persist as long as the pH remains acid (several weeks). = When the pH becomes neutral (remaining so until puberty), a mixed flora of cocci and bacilli is present. ™ At puberty, aerobic and anaerobic lactobacilli reappear in large numbers and contribute to the maintenance of acid pH through the production of acid from carbohydrates, particularly glycogen.preventing the establishment of other, possibly harmful microorganisms in the vagina. » © If lactobacilli are suppressed by the administration of antimicrobial drugs, yeast or various bacteria increase in the numbers and cause irritation and inflammation = After menopause, lactobacilli again diminish in number and a mixed flora returns.= The normal vaginal flora often includes also group B hemolytic Streptococci, anaerobic Streptococci (peptostreptococci), Prevotella species, Clostridia, Gardnerella vaginalis, Ureaplasma urealyticum, and sometimes Listeria or Mobiluncus species. . = The cervical mucus has antibacterial activity and contains lysozyme. ™ Vaginal organisms present at time of delivery may infect the newborn (eg. group B streptococci).Lactobacilli in the oral cavity probably contribute to acid formation that leads to dental caries. = Lactobacillus acidophilus colonizes the vaginal epithelium during child-bearing years and establishes the low pH that inhibits the growth of pathogens.I Streptococcus pyogenes Often found - mouth and throat. S.mutans,S. gordonii , and S. salvarius (normal mouth). blood agar used for hemolytic patterns Streptococcus pyogenes - Group A, Beta-hemolytic streptococci. ™ Cause tonsillitis (strep throat), pneumonia, endocarditis. Some streptococcal diseases can lead to rheumatic fever or nephritis which can damage the heart and kidney.SS Staphylococcus = S. aureus tends to be found in moist environme such as nose and armpits ® S. epidermidis is found on dryer areas of the ski and is rarely pathogenic. = Mannitol salt agar differentiates between them - i ferments mannitol and turns yellow it is S. aureus if not does not change it is S. epidermidis. \Se Neisseria meningitidis = Neisseria and other Gram-negative cocci - frequent inhabitants of the upper respiratory tract, mainly the pharynx. ™ Neisseria meningitidis - important cause of bacterial meningitis. ™ Grows on chocolate media ™ Oxidase positiveSS Diphtheroids (Coryneforms = Non-pathogenic members of the genus Corynebacterium are also normal skin humans. = Mueller-Hinton-Tellurite (MHT) plates - If diphtheroids are present, they will produce gray black colonies because they are able to reduce the tellurite in the media to tellurium, which appears ¢ a gray or black precipitate.Sh E. = E£. coli - a consistent resident of the small intestine. Klebsiella, Enterobacter and Citrobacter also seen = Some strains of £. coli are pathogens that cause intestinal infections, urinary tract infections and neonatal meningitis.SS Pseudomonas aeruginosa = The commonest opportunistic pathogen of humans that can invade virtually any tissue. ™ Leading cause of hospital-acquired (nosocomial) Gram-negative infections, but its source is often exogenous (from outside the host).SS Effects of broad-spectrum antibiotics on the normal flora Normal flora (normal microbiota) ™ (a) the drug destroy the friendly/helpful bacteria (normal microbial flora) ™ (b) Because they have such a wide spectrum of activity, [tetracyclines] destroy the normal intestinal microflora and often produce severe gastrointestinal disorders Superinfection ™ (a) Knocking out these non-pathogenic bacteria can lead to disease (e.g., diarrhea, Clostridium difficile -associated colitis, Candida vaginal yeast infections, etc.)® (b) Normal flora can compete with pathogenic bacteria (microbial antagonism), thus preventing disease; removing these flora can thus make an individual more susceptible to subsequent disease a (c) The replacement of a normal flora member by a pathogen is called superinfectionBENIFICIAL EFFECTS OF NORMAL MICRBIOTA . Prevent colonization by pathogenic organism: Occupy receptor site on skin & mucous membrane. . Antimicrobial substance production: Normal microbiota of the skin may produce bacteriocines & acids. . Normal microbiota in colon produce several vitamin B, vitamin K & vitamin E. . Stimulus for the development of the immune system: Bacterial colonization of the new born infant acts as a powerful stimulus for the development of the immune system. . Lactobacillus in vagina cause acidic pH that prevent growth of other microorganisms. . Disposal of its waste matter: Bacteria normally present in gut degrade mucins, epithelial cells, carbohydrate and fiber.HARMFUL EFFECTS OF NORMAL MICRBIOTA ac Causes serious infection in immunocompromised individual. Changes of normal anatomic location of normal microbiota may cause disease. Example: E. coli- normal microbiota in gut cause UTI when introduced by catheter. Creates problem in establishing accurate diagnosis. Inflammatory bowel disease and colorectal cancer: due to alterations of normal microbiota. Example: Akkermansia muciniphila & Bacteroid fragilis Colorectal cancer due to alterations of normal microbiota. Example: Bacteroid fragilis: Colorectal tumourPro-biotics Live bacteria! Pre-biotics Food for bacteria! Syn-biotics Synbiotics are a combination of both pro and prebiotics. Probiotics are active bacterial cultures. Prebiotics are substances that can only be metabolised by the gut bacteria, and not the human host.LT, REFERENCE BOOK 1. Review of Medical Microbiology and Immunology by Warren Levinson. 2. Medical Microbiology by Jawetz, Melnicls Adelberg's. \ 3. Medical Microbiology by Patrick R. Murray, S. Rosenthal and Michael A. Pfaller.