Biol371 Lecture 18 2023 PDF

Microbial symbiosis with humans (Ch 24) Relevant study questions in Chapter 24 of Brock. Review questions: 24.1-24.8, 24.10 Microbial symbioses with humans -- All sites on a human that contain microorganisms are part of a microbiome. -- A microbiome is a functional collection of different microbe...

Microbial symbiosis with humans (Ch 24) Relevant study questions in Chapter 24 of Brock. Review questions: 24.1-24.8, 24.10 Microbial symbioses with humans -- All sites on a human that contain microorganisms are part of a microbiome. -- A microbiome is a functional collection of different microbes in a particular environmental system (e.g., the human microbiome). -- Scientists use the term microbiota to describe all the microbes in a microhabitat (e.g., skin microbiota). -- Different microhabitats support different microbes, so the skin will have very different microbes than the mouth. Overview of the human microbiome There are approximately 1013 microbes in the human microbiome living in complex communities. Heavily colonized body regions include: -- Gastrointestinal Tract -- Oral Cavity and Airways -- Urogenital Tracts -- The Skin Figure 24.1 Why study the human microbiome? Future benefits of knowing about the diversity and function of the human microbiome include: -- development of biomarkers for predicting predisposition to diseases -- personalized drug therapies and probiotics We are currently in the early days, but studies have revealed that there are complex interactions between host and its microbiota. Cause and effect are not well understood, as a person’s health, activities, and diet will also influence the microbiome Fundamental questions in human microbiome research There are currently a number of integrated projects underway to answer basic questions about the human microbiome. 1. Do individuals share a core human microbiome? 2. Is there a correlation between the composition of microbiota colonizing a body site and host genotype? 3. Do differences in the human microbiome correlate with differences in human health? 4. Are differences in the relative abundance of specific bacterial populations important to either health or disease? Cultivation independent studies have revealed microbiome diversity across body habitats Most Bacteria have not been cultured; however, advanced sequencing techniques allow for identification of different microbiota at different body sites. Figure 24.2 Cultivation independent studies have revealed microbiome diversity across body habitats There have been numerous metagenomic studies to determine the nature of the normal microbiota. Gastrointestinal microbiota The gastroinestinal tract is the most heavily colonized site. Microbes in gut affect early development, health, and predisposition to disease. Colonization of gut begins at birth. The gastrointestinal (GI) tract: Consists of stomach, small intestine, and large intestine; comprises 400 m2 of surface area Responsible for digestion of food, absorption of nutrients, and production of nutrients by the indigenous microbiota Contains 1013 to 1014 microbial cells Figure 24.3 The Stomach and Small Intestine The acidity of the stomach and the duodenum of the small intestine (pH 2) prevent many organisms from colonizing the GI tract; however, there is a rich microbiome in the healthy stomach. Firmicutes, Bacteroidetes, and Actinobacteria are common in the gastric fluid, while Firmicutes and Proteobacteria are common in the mucus layer of the stomach. Helicobacter pylori was discovered in the 1980s and has since been found in about 50 percent of the world’s population. When present, it is found in the gastric mucosa. H. pylori is a risk factor in development of ulcers and cancers The large intestine and colon The colon is essentially an in vivo fermentation vessel, with the microbiota using nutrients derived from the digestion of food. Most organisms are restricted to the lumen of the large intestine, while others are in the mucosal layers. Figure 24.6 Bacterial diversity in the large intestine and colon The gut microbiota is composed of only a few phyla, and is distinct from any other microbial community A couple hundred “species” in any one individual, thousands of species in the human population Vast majority of all phylotypes are within the Bacteroidetes and Firmicutes Bacteria we tend to think of as gut bacteria such as E. coli only make up a tiny fraction of the diversity and abundance Figure 24.5 Gastrointestinal microbiota: gut enterotypes Individuals may have mostly Firmicutes, mostly Bacteriodetes, or a mix of the two. This may regulate metabolism and the host’s propensity for obesity. While individuals vary in their gut microbiota, each individual has a relatively stable gut microbiota. There are three basic enterotypes currently being studied: #1 is enriched in Bacteroides, #2 is in Prevotella #3 is enriched in Ruminococcus. Early studies indicate that each enterotype is functionally as well as phylogenetically distinct Products of Intestinal Microbiota and “Educating” the Immune System Many microbial metabolites or transformation products that can be generated in the gut have significant influence on host physiology. 1. vitamin production 2. modification of steroids 3. amino acid biosynthesis Production of “symbiosis factors” by bacteria, such as oligosaccharides that signal to the immune system to promote tolerance of beneficial microbes Microbiota of the oral cavity The oral cavity is a complex, heterogeneous microbial habitat. Saliva contains antimicrobial enzymes. The tooth consists of a mineral matrix (enamel) surrounding living tissue, the dentin, and pulp. But high concentrations of nutrients near surfaces in the mouth promote localized microbial growth. A high diversity of bacteria is found in oral plaque and play a role in dental diseases (Figure 24.8) Fig 25.8 Microbiota of the airway Microbes thrive in the upper respiratory tract. Figure 24.10 Bacteria continually enter the upper respiratory tract from the air during breathing. Most are trapped in the mucus of the nasal and oral passages and expelled with nasal secretions or swallowed and then killed in the stomach. The lower respiratory tract has no normal microbiota in healthy adults. Ciliated mucosal cells move particles up and out of the lungs. Potential pathogens such as Staphylococcus aureus and Streptococcus pneumoniae are in the airway and can cause disease in those with a compromised immune system Microbiota of the urogenital tracts In healthy individuals the kidney and bladder are sterile, but the epithelial cells of the urethra are colonized by facultative aerobes. Altered conditions can cause potential pathogens in the urethra (such as Escherichia coli and Proteus mirabilis) to multiply and cause disease. E. coli and P. mirabilis frequently cause urinary tract infections in women. The vagina of the adult female is weakly acidic and contains significant amounts of glycogen. Lactobacillus acidophilus, a resident organism in the vagina, ferments the glycogen, producing lactic acid. Lactic acid maintains a local acidic environment. (Figure 24.11) Microbiota of the skin There are approximately 1 million resident bacteria per square centimeter of skin for a total of about 1010 skin microorganisms covering the average adult. The skin surface varies greatly in chemical composition and moisture content and can be categorized into three distinct microenvironments 1. dry skin 2. moist skin 3. sebaceous skin The skin microbiota is influenced by many factors including environmental factors, age, hygiene, level of activity… Figure 24.13 Microbiota of the skin There are approximately 1 million resident bacteria per square centimeter of skin for a total of about 1010 skin microorganisms covering the average adult. The skin surface varies greatly in chemical composition and moisture content and can be categorized into three distinct microenvironments 1. dry skin 2. moist skin 3. sebaceous skin The skin microbiota is influenced by many factors including environmental factors, age, hygiene, level of activity… Figure 24.15 Microbiota of the skin How do we become colonized with microbes? Community succession occurs over the first couple years, and an adult-like community develops by the age of three Vaginal Delivery • First major step in microbial colonization • Massive fetal exposure to maternal vaginal, fecal (and skin) microbiota – Bifidobacterium species from the mother’s prenatal feces in the feces of infants born vaginally (but not by Csection) – A study of women at 35–37 weeks of gestation showed that many bacteria, including Lactobacillus and Bifidobacterium species, are shared between the rectum and the vagina Changes in the gut microbiota during pregnancy • Vaginal microbiota + gut microbiota both change during pregnancy • Vaginal microbiota â diversity – Dominance of lactobacilli á with gestational age – Adaptive changes – lactobacilli maintain low pH à limit bacterial diversity à prevent bacteria from ascending to the uterus • Gut microbiota â diversity – Dominance of high-energy-yielding fecal microbiota á with gestational age – Adaptive changes - greater energy harvest during pregnancy to support the growth of mother and fetus Cell2012 2012150, 150,470-480DOI: 470-480DOI:(10.1016/j.cell.2012.07.008) (10.1016/j.cell.2012.07.008) Cell Breastmilk • Composition: 1. Lactose 2. Fats 3. Over 200 human milk oligosaccharides (HMO) • But HMOs can NOT be digested by babies… • Why would lactating females waste so much energy synthesizing HMOs? • HMOs are metabolized by bacteria in the large intestine, esp. Bifidobacterium longum infantis – Promotes gut epithelia cell-to-cell adhesion – Produces sialic acid, necessary for brain development • Social primates have more oligosaccharides than solitary ones – Protects against pathogens as HMOs resembles gut glycans Stability of the adult microbiome and transitions with age Mouse models for investigating the impact of the gut microbiome on health and development Mice have a short life cycle and well-defined genetic lines and you can do experiments with them that can not be performed on humans. Research can be done to explore: Mouse models for investigating the impact of the gut microbiome on health and development Mice have a short life cycle and well-defined genetic lines and you can do experiments with them that can not be performed on humans. Research can be done to explore: 1) The importance of host genetic background through selective gene knockout 2) Effect of microbiota community composition using germ free mice colonized with different bacteria 3) The influence of tightly controlled diets 4) The consequences of antibiotic treatment 5) Transfer of physiological traits through fecal transplants The Role of the Gut Microbiota in Obesity The Role of the Gut Microbiota in Obesity Normal mice have 40 percent more fat than germ-free mice with the same diet. When germ-free mice were given normal mouse microbiota, they started gaining weight. Mice that are genetically obese have different microbiota than normal mice. Obese mice have more Firmicutes and often more methanogens Figure 24.19 The Gut Microbiota and Human Obesity Like the mouse model, obese humans have more Firmicutes than non-obese humans. Studies in obese/lean twins have shown that transfer of the gut microbiota to mice will influence the obese phenotype The nature and transferability of gut microbiota is dependent on diet as well as genetics. Figure 24. 20 Disorders Attributed to the Human Microbiome: Irritable bowel disease (IBD) and irritable bowel syndrome (IBS) Microbiota in IBS • Heterogeneous clinical presentation (IBS-D, IBS-C) – Diarrhea predominant, constipation predominant – Low grade inflammation only in a subset of patients • Changes reported in diversity, temporal stability and metabolic activity of microbiota in IBS patients • NO consistent microbiotic signature in IBS • Most consistent finding = â diversity – á Firmicutes, â Bacteroidetes – â Bifidobacteria in IBS-D • Transplant of IBS microbiota to germ-free rats = á visceral hypersensitivity • Transplant of IBS microbiota to germ-free mice = á GI transit + intestinal permeability • IBS : á colonic VFAs produced by bacteria, correlates with á symptom severity Microbiota-gut-brain axis maternal Immune Activation (mIA) and neuronal dysfunction • mIA involves elevated levels of inflammatory factors in the blood, placenta, and amniotic fluid during pregnancy that can be caused by viral or bacterial infection • Animal models have shown mIA to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring • Human epidemiological studies have shown an association between maternal infection and neurodevelopmental disorders • For example, mIA is an environmental risk factor for a child developing autism Influence of the gut microbiota on autistic-like behavior poly I:C is an immunostimulant, used to simulate viral infections and mIA offspring in mice Anxiety like behavior in MIA mice The defect is ameliorated in mice fed with B. fragilis, perhaps through displacement of the EPS producing bacteria This chemical alone can induce anxiety like behavior in mice Can the microbiome influence aging? Modulation of the Human Microbiome: antibiotics Oral antibiotics decrease ALL microbes in the human gut (both target and nontarget). Use of antibiotics during the first few months of life increases the risk of developing IBD and other disorders related to dysbiosis. Clostridium difficile infections are associated with antibiotic use. Clostridium difficile is a spore-former and generally antibiotic resistant. A newer therapy for Clostridium difficile infection is a fecal transplant. Figure 24.23 Modulation of the Human Microbiome: Probiotics and Prebiotics Probiotics are live organisms that confer a health benefit to the host. Prebiotics are typically carbohydrates that are indigestible by human hosts, but provide nutrition for fermentative gut bacteria.