Human Microbiota Lecture 4 PDF

Aurora Killi Human microbiota Lecture 4 The humane microbiome is the population of all microbiotas that reside on our within human tissues and biofluids along with the corresponding anatomical sites in which they reside Terminology Microflora → the term microflora is used frequently, yet it i...

Aurora Killi Human microbiota Lecture 4 The humane microbiome is the population of all microbiotas that reside on our within human tissues and biofluids along with the corresponding anatomical sites in which they reside Terminology Microflora → the term microflora is used frequently, yet it is not precise as it was conceived when only two kingdoms existed, namely Animalia and Planta. Microbiomes were classified under Planta, therefore the term flora Microbiota → total number of microorganisms found at a given area Microbiome → genomes of microbiota. We use this term when we perform genome examination Metagenomics → direct study of genetic material recovered from microbial communities. Communities means that we cannot separate one microbe from another, so when we take a DNA sequence, we get the DNA sequence of many bacteria at the same time Facts The intestinal microbiota contains 3.3 million genes The human genome consists of around 22 000 genes o Big difference between genes in intestinal tract Genetic similarity among humans is 99.9% Difference between people´s intestinal and skin microbiome is 80-90%. This means that our microbiome is unique and very individual Here you can see a map of diversity in the human microbiome o E. coli is present in the gut of majority of healthy subjects o Staphylococcus epidermitis colonies resides on the skin Classification of microbiota 1. Resident or constant (obligatory) microbiota → fixed types of microorganisms found in a given area at a given age 2. Transient microbiota (facultative) → non-pathogenic or potentially pathogenic microorganisms that inhabit the skin or mucous membrane for hours, days, weeks. These microbiota pass through a region and resides there for hours, days, or weeks Ecological niche One niche is one particular area or site of the body with a group of typically found microbes Microorganisms in different areas of the body The variety of microorganisms species differs An adult body harbors 1013 bacteria There are 350 species of microbes in the large intestine There are two factors that determine the formation of ecological niches o Bacterial adherence → adhesins. Bacteria are subject to saliva, chewing food, gastrointestinal juices, intestinal peristalsis, etc. o Environmental conditions → O2, humidity, nutrients, T, pH, etc.) Ecological niches have a crucial role in human microbiota 1  Aurora Killi If person has some microbe disbalance in a concrete region of the body, it could be associated as one from many that promotes development of disease o Example 1: changes in the oral microbiome could lead to dental caries o Example 2: changes in the skin microbiome can promote ectopic dermatitis When does microbiota appear? The fetus is sterile Newborns are colonized during delivery Within 4-12 hours → nonhemolytic bacteria o Viridian streptococci are the first colonizers of the newborn. Nonhemolytic means that these bacteria do not cause red blood cell lysis if they are cultivated on blood agar. The term viridians streptococci mean green streptococci, and this means that for these agents there are no hemolytic zone around the colonies. And the zone has a slightly greenish color o Streptococcus mutans o S. mitis o S. salivarius Within 24-48 hours → microbiota of intestinal tract o Lactobacillus o Bifidobacterium spp. o Coliform bacteria In breast-fed children those microbes produce acid from carbohydrates and tolerate pH 5 In bottle-fed children, a more mixed flora exists in the bowel. Lactobacilli are less prominent Maternal and postnatal factors There are factors that can influence the concentration and content of microbiota. They are subdivided into two groups Maternal factors → can influence newborn microbiota o Gut microbiota o Vaginal infection o Periodontitis Postnatal factors o Antibiotics o Breast-feeding o Host genetics o Environment o Diet (especially in the later periods after first year of age, because microbiota can change if some products lack) Interaction of microorganisms and the host Microbes: There are a lot of microbes in different sites Infect the host: They contact with the host, and they can infect the host as well Carrier state: the person at first becomes a carrier and this is called a carrier state. Carrying also means that there are no clinical signs or symptoms. But if person is in contact with other susceptible people, the carrier might become a source of infection to surrounding people. Carrier state is subdivided into two groups o Acute carrier o Chronic carrier → according to data, overall people are chronic carriers for o Staphylococcus aureus (20-40%) o Streptococcus pneumoniae (40-70%) o S. typhi u. 2  Aurora Killi Exposure of an individual to a microorganism can lead to 1. The microbe can transiently colonize the person Microbes that colonize humans do not 2. Permanently colonize the person disrupt normal body functions 3. Produce disease Disease occurs when the infraction between microbe and human leads to a pathogenic process characterized by damage the human host Causative agents of infectious diseases Pathogens are divided into two groups 1. Strict pathogens → microbe always associated with disease in humans M. tuberculosis N. gonorrhoeae Fr. tularensis Plasmodium spp. Rhabdovirus 2. Opportunistic pathogens → microbes that are typically members of the patient´s normal microbiota. These organisms do not produce disease in their normal setting, but cause disease when they are introduced into unprotected sites (e.g., blood stream, tissues) S. aureus E. coli C. albicans Risk factors for opportunistic infections Immunodeficiency Chronic diseases (diabetes) Gastric ulcer Stress Antibacterial treatment Malnutrition Avitaminosis etc. Skin microbiota Transient microbiota → surficial Resident microbiota → constant in deeper parts of the skin There are approx. 103-104 microbes per cm2 Most typically we see members such as o Staphylococcus epidermidis (90%) o Corynebacterium o Cutibacterium acnes o Malassezia o Candida Factors influencing skin microbiota Detergents → transitory and superficial constant microbiota is decreased by 90%. Recolonization happens within 8 hours Disinfectants → kill resident microbiota Sex Age Climate UV rays 3  Aurora Killi Hygiene Profession Diseases Intact skin is the first line of defense against microbial invasion Skin is dry (not suited for microbial growth), yet it has microbiota that is supplied with nutrients by 1. Sweat glands → there are two kinds Eccrine glands secrete sweat Apocrine glands secrete sweat and nutrients. these are more active following puberty Sweat glands secrete o Lysozyme which cleaves the bond between NAG and NAM in peptidoglycan o Lactic acid which lowers pH to 3-5 and suppresses microbial colonization 2. Sebaceous glands → attached to hair follicles Secrete sebum Microbes multiply up to 106/cm2 Skin mycobiome Skin mycobiome is another term that characterizes normal fungal species in this region Fungi represent 30% of the skin microbiota and Malassezia strains are by far the majority on the skin o M. globosa o M. restricta o M. furfur etc. Malassezia represents more than 90% of fungal population in most skin niches The role of Malassezia on the skin remains controversial because this genus has been associated with both healthy skin and pathologies such as dandruff, eczema, etc. Human virome Human virome is a collection of all the viruses found in or on human organs such as the skin Human stools contain at least 109 virus-like particles (VLPs) per gram Bacteriophages make up 96.1% of the human gut viral populations Human virome potentially influences human health, not only disease Microbiota of nasopharynx and oropharynx Nasopharynx Oropharynx Microbe amount: 105/ml Microbe amount: 107/ml Staphylococcus epidermidis Staphylococcus Corynebacterium Streptococcus Propionibacterium Corynebacterium Haemophilus parainfluenzae Propionibacterium Neisseria spp. Pathogens Branhamella catarrhalis Staphylococcus aureus Bacteroides Staphylococcus pneumoniae Fusobacterium anaerobes Haemophilus influenzae Enterococcus Neisseria meningitidis Pathogens Streptococcus (α-hemolytic) 4  Aurora Killi Corynebacterium diphtheriae Klebsiella pneumoniae Pseudomonas aeruginosa Microbiota of oral cavity Microbe amount in saliva: 108/ml Microbe amount in teeth plaque: 1011/g Streptococcus salivarius o S. sanguis o S. milleri o S. mutans Staphylococcus Enterococcus Veilonella Neisseria Bacteroides orale Fusobacterim nucleatum Leptrotrichia buccalis Actinomyces Vibrio Spirocheta o Treponema orale o Borrelia buccalis o Leptospira dentium Candida albicans o Saccharomyces Prevotella malinogenica Porphyromonas gingivalis etc. Dental caries Polyaethiologic disease Caries is disintegration of the teeth beginning at the surface and progressing inwards The surface enamel is demineralized caused by acid products of bacterial fermentation Subsequent decomposition of the dentin and cement Microbial mechanism of caries 1. After a meal, there is produced around 0.1 um saliva layer which also is called microbe pellicle on the surface of the teeth 2. The microbe pellicle is a good place for the bacteria to attach 3. If we give time for the pellicle to grow, the microbes remain, multiply and cleave carbohydrates to produce glucan and fructan 4. They generate pH decrease, and promote anaerobic conditions because of extensive bacterial metabolism 5. It leads to conditions that this environment is good for facultative anaerobes and even anaerobes 6. Lactobacillus makes environment even more acidic because they produce lactic acid 7. So high concentration of lactic acid promotes demineralization and initiates dental caries 8. Dental caries is also a biofilm where bacteria are protected from immune cells and antibiotics 5  Aurora Killi Gastrointestinal microbiota Stomach o pH 1-3 o 101-103 CFU/ml o PO2 77 mmHg o Lactobacillus, Streptococcus, Staphylococcus, Enterobacteriaceae Duodenum o 101 – 103 CFU/ml o PO2 33 mmHg o Lactobacillus, Streptococcus, Staphylococcus, Enterobacteriaceae Small intestine Jejunum and ileum pH 6-7 4 7 o 10 – 10 CFR/ml o PO2 33 mmHg o Bifidobacterium, Bacteroides, Lactobacillus, Streptococcus, Enterobacteriaceae Colon o pH 7 o 1010 – 1011 CFU/ml o PO2 < 33 mmHg o Fusobacterium, Eubacterium, Clostridium, Peptostreptococcus, Bifidobacterium, Streptococcus, Bacteroides, Lactobacillus, Enterobacteriaceae Gut-brain-microbiota axis Gut microbiota variations play a critical role in the pathogenesis of neuropsychiatric disorders Communication along this axis is bidirectional Antibiotic courses for patients with GI diseases can increase the burden of depression and anxiety symptoms Gut microbes provide neuroactive compounds and immune modulators including serotonin, dopamine, y-aminobutyric acid, acetylcholine, histamine, and short-chain fatty acids Urogenital microbiota Vagina Urethra 109/ml Staphylococcus epidermidis Staphylococcus epidermidis Peptostreptococcus Streptococcus Neisseria spp. Corynebacterium spp. Lactobacillus acidophilus Lactobacillus fermentans Bacteroides Ureaplasma Mycoplasma The role of microbiota Positive aspects o Absorption of nutrients and breakdown of products o Synthesis of vitamin K o Conversion of bile pigments and bile acids o Antagonism to microbial pathogens o Stimulation of the immune system Negative aspects → may cause disease if 6