Microbiome lecture.pdf

THE MICROBIOME Katelyn Mroczek [email protected] WHAT IS THE MICROBIOME? Learning outcomes Define what is meant by the term ‘microbiome’ Understand the development of the microbiome Difference between resident and transient microflora ...

THE MICROBIOME Katelyn Mroczek [email protected] WHAT IS THE MICROBIOME? Learning outcomes Define what is meant by the term ‘microbiome’ Understand the development of the microbiome Difference between resident and transient microflora  What is a Microbiome? A functional collection of different microbes in a system Genetic material from all the microbes in and on the human body Includes bacteria, viruses, fungi, protozoa Number of genes in a human microbiome is 200 x the number in the human genome (The Center for Ecogenetics and Environmental health, University of Washington) Can weigh up to 2kg!! Picture: Gaby D’Allesandro / American Museum of Natural History  Microbiome vs Microbiota Microbiota: Defined by over 100 experts from all over the world in 2020 Encompasses: Prokaryotes and eukaryotes Comprise of microbial structures, metabolites, and movable genetic elements Microbiomes encompass a wider range than microbiota. Included in the microbiome that are NOT members of the microbiota Phages Viruses Plasmids Free DNA Prions Viroids Tai, J., Han, M. S., Kwak, J., & Kim, T. H. (2021). Association between Microbiota and Nasal Mucosal Diseases in terms of Immunity. International Journal of Molecular Sciences, 22(9), 4744. Retrieved from https://www.mdpi.com/1422-0067/22/9/4744 https://res.mdpi.com/d_attachment/ijms/ijms-22-04744/article_deploy/ijms-22-04744-v2.pdf The human https://www.hmpdacc.org/ microbiome project Goal – to catalogue all the microorganisms of the human body An extension of the human genome project Sponsored by the National Institutes of Health (NIH) U.S.A Study of major microbial sites of the human body of 300 healthy individuals Skin Mouth Nose Colon Vagina  THE MICROBIOME IS HIGHLY Microbiomes of individuals are PERSONALISED unique Estimates of 80- 90% different from each other Our human genomes are 99.9% identical 22000 human genes vs 3.3 million genes in the gut microbiome Gilbert, Jack A, Blaser, Martin J, Caporaso, J Gregory, Jansson, Janet K, Lynch, Susan V, and Knight, Rob. "Current Understanding of the Human Microbiome." Nature Medicine. 24.4 (2018): 392-400. Web. Normal Microbial Microflora Micro-organisms that inhabit the skin and mucous membranes of a healthy human body Normal flora comprises both resident and transient microflora Transient microflora unlike resident m/o are not usually able to multiply Human body comprised of diverse habitats https://en.wikipedia.org/wiki/Human_microbiome#/media/File:Skin_Microbiome20169-300.jpg  Our microbiome develops over time At birth neonate – blood, tissues, amniotic fluid is microbe free Colonisation occurs rapidly due to contact with birth canal, carers & hospital environment Breast- or bottle-feeding results in development of different microflora ▪ a – haemolytic Strep colonize 4- 12hrs after birth S. aureus colonisation within few days https://mmbr.asm.org/content/81/4e00036-17 9  Development of microflora in newborn babies Bifidobacterium predominant organism in breast fed newborn babies Together with lactobacilli comprises 90 -99% faecal population Bottle fed babies have mixed & varied population of microbes Bifidobacterium found in vagina of pregnant women and in colostrum of lactating mothers https://www.researchgate.net/figure/Stages-of-microbial-colonization- of-the-infant-and-child-intestine-Most-abundant_fig1_266086347 10 Resident vs Transient microflora Resident: population of cells permanently found on or in human body at any time Re-established if removed Microbial antagonism Competition with pathogens for nutrients Transient: microbes that only reside in any given area for a short period of time Environment dependent Hours, days, weeks Insignificant unless resident flora affected Pathogenic & potentially pathogenic m/o https://ubiome.com/blog/post/nail-biting-truth- hands-bacteria/ 11  A handprint from an eight-year-old boy after he came in from playing outside (Tasha Sturm, Cabrillo College via ASM) MICROBIAL POPULATIONS OF THE BODY Learning outcomes Know the main microbial populations at each body site Understand how skin microbes can prevent colonisation of pathogens Normal Human Microflora Microbiota May include pathogens (organisms that cause disease), even when there are no symptoms of disease Only transient in: Eyes, Upper urinary tract, Kidneys, bladder In low numbers: Respiratory tract: -lungs, trachea 14 Skin Largest organ of the human body The skin can vary dramatically from person to person Varying characteristics (1) Ultraviolet light Sebaceous Moist Dry exposure and oily pH Face, chest, Bend of Volar forearm Topography back elbow, back of and palm Temperature knee, groin Moisture Sebum content  Interactions with resident skin flora and S. aureus Antibiotics produced by coagulase negative Staphylococcus sp. prohibit colonisation S. epidermidis can prevent S. aureus biofilm Epidermidis forming Protease production also signals immune response – producing antimicrobial peptides = Kills S. aureus Propionibacterium produces small molecules that promote S. aureus aggregation and biofilm formation Byrd, A. L., Belkaid, Y., & Segre, J. A. (2018). The human skin microbiome. Nature Reviews Microbiology, 16(3), 143-155. doi:10.1038/nrmicro.2017.157 The foot The microbiota of the feet are quite different to other areas of the skin The feet are home to more species of fungi than other places on the body Typical bacteria of the feet are Corynebacteriaceae, Micrococcacea and Probionibacteriacea The most common fungi: Malassezia, Cryptococcus, Aspergillus, Trichophyton, Candida  Nasal cavity (middle meatus) Nose and upper Anterior nares respiratory The nose has a similar microbial make up to the skin However, 20-30% of the Divided into 3 categories Non carriers 50% population carry S. aureus Persistent carriers 20% in the nose Transient carriers 30% Can be antibiotic resistant strains  The eye The number of bacteria on the surface of the eye is quite low The eye has many natural defence mechanisms against microbes Lysozyme Tear film contains Antimicrobial peptides Immunoglobulins (antibodies) Most common microbiota: Propionibacterium, Corynebacteria, Staphylococcus, Streptococcus Li, J. J., Yi, S., & Wei, L. (2020). Ocular Microbiota and Intraocular Inflammation. Frontiers in Immunology, 11(3388). doi:10.3389/fimmu.2020.609765  Microbial flora of the GIT form 1 kg of our body weight! 60% of the dry mass of feces! 20  BENEFITS OF THE MICROBIOME Learning outcomes Describe the benefits of the microbiome/normal microflora BENEFITS OF THE MICROBIOME  Normal Flora - benefits Established resident flora forms barrier to invasion or colonisation by either external pathogens or internal opportunists Bacterial Interference – mode of action unknown: possible mechanisms Competition for nutrients Host cell receptor binding sites Resident m/o growth forms protective layer across tissue surfaces eg intestine Production of inhibitory substances fatty acids, bacteriocins, colicins, metabolic waste products, antibiotic production eg Acid environment maintained in vagina by lactobacilli suppresses growth of other microbes 23  Benefits of normal body flora Stop harmful bacteria & fungi from invading the body → compete for attachment receptors & food sources → maintain a low pH – to prevent fungal growth (skin, mucous membranes, female genital tract) e.g. Lactobacillus species → acid fermentation = low pH (acidic) → protection from invasion of harmful microbes https://fineartamerica.com/featured/lactobacillus- acidophilus-dennis-kunkel-microscopyscience- 24 photo-library.html  Benefits of gut bacteria Harvesting nutrients from food Able to break down certain nutrients (e.g. carbohydrates) that humans otherwise could not digest 30% of calories processed by bacterial in the gut Gut flora produce vitamin K Essential for normal blood clotting https://dailylolpics.com/at-least-if-youre-feeling-full- Produce chemicals (signalling molecules) youre-feeling-something Tell us when we are hungry/full Neurotransmitters - serotonin Involved with immune system and metabolic function Balance good vs bad bacteria 25 DIGESTION OF AN APPLE WITH AND WITHOUT MICROBIOME FACTORS THAT AFFECT THE MICROBIOME Learning outcomes List and understand how different factors can affect the microbiome  Factors affecting normal flora Sex Diet Standard of living Nutritional status Health Drugs, antibiotic therapy Hospital stay Clothing Environment Including family & friends in https://www.biokplus.com/en_us/about-probiotics close contact with individual 28 Factors affecting microbiome Diet Long term diets affect gut microbiome Microbial diversity in the gut varies with a diet rich in plants/vegetables/fruit Limited diet = low microbial diversity Age Increased age = decreased microbial diversity This correlates with inflammation and frailty Younger individuals have a greater proportion of gram-negative bacteria of faecal origin Factors affecting microbiome - Lifestyle Cohabitation with pets Children raised with pets less likely to develop allergies Exposure to dogs can alter the gut microbiome Dust from homes from dogs reduce immune response to asthma triggers Couples that live with a dog have similar microbiomes  Factors affecting microbiome - Lifestyle Exercise Reduces inflammation Sleep deprivation Been seen to correlate with gut microbiome Stress Changes microbiome with increased permeability of intestine Occupation E.g. Farmers vs Office workers significantly different microbiomes https://tenor.com/search/sleep-deprived-gifs ILLUSTRATION: DARIA KIRPACH https://tenor.com/view/bart-the-simpsons-stressed-problem-gif-12954832 https://www.nytimes.com/guides/business/manage-your-career Antibiotics Antibiotics can affect normal microbiota as well as the targeted pathogens Can lead to a significant change in normal microflora Gut Vaginal Skin When administered early on in development can cause problems Developing normal microflora Development of the immune system Can predispose child to allergies and autoimmune disorders Probiotics and Prebiotics Prebiotic: specific plant nutrients Carbs humans can’t digest Bacterial food source Acts as a microbial growth stimulant Probiotic: contains live microorganis m s W hen consumed can potentially provide a health benefit to the host Eg. Bifidobacterium spp. and Lactobacillus spp. In yoghurt etc Terms Microbiome Microbiota Transient flora Resident flora Biofilm Antibiotic Prebiotic Probiotic DISADVANTAGES OF THE NORMAL FLORA Learning outcomes Understand the difference between pathogenic and non-pathogenic organisms Understand and apply key microbiological terms 35  Normal Flora - disadvantages Provides ready source of potential pathogens to possibly cause infection and disease Microbes displaced or that spread from natural habitat may result in infection Large intestine to vagina, mouth Nose to mouth Skin to hair follicle Open wound, break in skin due to trauma or surgery URT to bloodstream Mouth to bloodstream (dental treatment) http://www.microbiologynutsandbolts.co.uk/normal-flora.html Do all Microbes cause disease? No!! Microorganisms that cause disease are called pathogens Most microorganisms are non-pathogenic Pathogens are usually host-specific eg. Human versus feline AIDS 37 Pathogens causing disease Pathogens usually cause a specific disease Yersinia pestis causes bubonic plague (the black death) Neisseria gonorrhoea causes Gonorrhoea Treponema pallidum causes Syphilis Vibrio cholerae causes cholera 38  Pathogens causing disease Some pathogens cause a more severe disease than others eg. Virulent Flu strains vs less virulent strains. https://en.wikipedia.org/wiki/Meninges Different pathogens may cause a similar disease eg. Meningitis: Bacterial – N. meningitidis, H.influenzae type b., Streptococcus pneumoniae Viral – most common, various types, no specific treatment Other types – amoebic, fungal Overview of the meninges, and their relationship to the skull and brain. 39 Many beneficial microbes are … potential pathogens! Proliferation of potential pathogen due to imbalance caused by: Altered or weakened physical and/or immunological state Due to disease, surgery, immunosuppression Medical treatment antibiotic treatment Corticosteroid therapy Change in normal habitat pH change in stomach or vagina http://www.microbiologynutsandbolts.co.uk/normal-flora.html 40  Contamination,Colonisation andInfection Contamination - microbe has been introduced into the microbiology sample from an external source. Colonisation ≠ Infection normal process which occurs when bacteria grow on body sites. Infection - microbes can cause damage to body tissues. Infection may not involve any apparent symptoms 41 Slide 41 | Version 2 Colonisation – GIT Most microbes will not survive the conditions to which they are exposed to in the gut and will die off Micro-organisms can gain entry by protection from food entering body Establishment of infection is also dependent on the number of m/o ingested Invasins allow m/o to bypass some of these conditions and establish disease 42 OPPORTUNISTIC PATHOGENS Learning outcomes Understand opportunistic pathogens and the types of infections they can cause Understand the portals of entry 43  Microbiota - Medical Significance Many beneficial microbes are … potential pathogens! ‘Opportunistic’ pathogens can be: Normal flora But ALSO those from environment e.g. soil Given the ‘right’ opportunity…they may cause disease faecal bacteria: in mouth, eyes, urogenital tract contamination of wounds: surgery, injury increased risk of infection in: AIDS, chemotherapy, organ transplants, immune disorders 44 © University of East Anglia  Portals of entry Mouth & gastrointestinal tract Respiratory tract Urogenital tract Skin Microbial source may be exogenous or endogenous 45 Candida albicans Habitat: mouth, digestive tract, and vagina Opportunistic pathogen Infection of the mouth, vagina, genital area, anus, armpits, skin under the breasts in women & skinfolds of the stomach Infection can arise: Following hot, humid weather Wearing tight, synthetic underclothing Poor hygiene Inflammatory diseases eg psoriasis, occurring in the skinfolds Antibiotics 46 Candida albicans Those at most risk Corticosteroids or immunosuppressive therapy following organ transplantation Inhaled corticosteroids used by asthma sufferers Most likely in pregnant women, obese people, and diabetics In some instances where individuals have a weakened immune system Candida may invade deeper tissues as well as the blood, causing life- threatening systemic candidiasis 47 Staphylococcus aureus Scalded Skin Syndrome Toxic Shock Syndrome Pimples, Boils, Styes Food Poisoning “Golden Staph” - Hospital acquired infection MRSA - superbugs 48 SKIN INFECTIONS 49 EYE INFECTIONS 50 NECROTISING FASCIITIS CAUSED BY S.AUREUS 51 Pseudomonas aeruginosa Found in almost any habitat Human/animal impacted environments Major cause of illness and deaths in the immunocompromised Most common cause of microbial keratitis in wearers of contact lenses Able to form biofilms (on contacts) Common pathogen in diabetic foot infection 52  Pseudomonas aeruginosa biofilm formation Billions of bacteria Clustered Covered with extracellular matrix Glued to surface Scott Chimileski and Roberto Kolter, Harvard Medical School 53 Terms Pathogenic Non-pathogenic Contamination Colonisation Infection Opportunistic pathogen 54