Lec#17 .pptx

PowerPoint® Lecture Presentations CHAPTER 24 Microbial Symbioses with Humans © 2018 Pearson Education, Inc. 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 particul...

PowerPoint® Lecture Presentations CHAPTER 24 Microbial Symbioses with Humans © 2018 Pearson Education, Inc. 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. © 2018 Pearson Education, Inc. OTU= operational taxonomic unit. (closely related individuals based on DNA sequence comparisons). © 2018 Pearson Education, Inc. © 2018 Pearson Education, Inc. Overview of major microbial populations in the body sites sampled by human microbiome projects. © 2018 Pearson Education, Inc. I. Structure and Function of the Healthy Adult Human Microbiome • • • • • 24.1 Overview of the Human Microbiome 24.2 Gastrointestinal Microbiota 24.3 Oral Cavity and Airways 24.4 Urogenital Tracts and Their Microbes 24.5 The Skin and Its Microbes © 2018 Pearson Education, Inc. 24.1 Overview of the Human Microbiome • There are approximately 1013 microbes in the human microbiome living in complex communities. © 2018 Pearson Education, Inc. Figure 24.1 24.1 Overview of the Human Microbiome • Future Benefits of Knowing the Human Microbiome • development of biomarkers for predicting predisposition to diseases • designing targeted therapies • personalized drug therapies and probiotics • These are very early studies, and they reveal that there are complex interactions between host and its microbiota. © 2018 Pearson Education, Inc. 24.1 Overview of the Human Microbiome • Experimental Protocols and Body Target Sites • Most Bacteria cannot be cultured; however, advanced sequencing techniques allow for identification of different microbiota at different body sites. • There have been multiple studies to determine the nature of the normal microbiota. © 2018 Pearson Education, Inc. 24.1 Overview of the Human Microbiome • There are currently integrated projects underway to answer basic questions about the human microbiome. • Do individuals share a core human microbiome? • Is there a correlation between the composition of microbiota colonizing a body site and host genotype? • Do differences in the human microbiome correlate with differences in human health? • Are differences in the relative abundance of specific bacterial populations important to either health or disease? © 2018 Pearson Education, Inc. 24.2 Gastrointestinal Microbiota • Humans are monogastric and omnivorous. • Microbes in gut affect early development, health, and predisposition to disease. • Colonization of gut begins at birth. © 2018 Pearson Education, Inc. 24.2 Gastrointestinal Microbiota • The human 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 microbial flora • Contains 1013 to 1014 microbial cells © 2018 Pearson Education, Inc. © 2018 Pearson Education, Inc. Figure 24.3 24.2 Gastrointestinal Microbiota • The Stomach and Small Intestine • Microbial populations in different areas of the GI tract are influenced by diet and the physical conditions in the area. • 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 ~50 percent of the world’s population. When present, it is found in the gastric mucosa. © 2018 Pearson Education, Inc. 24.2 Gastrointestinal Microbiota • Intestinal microorganisms carry out a variety of essential metabolic reactions that produce various compounds • The Large Intestine • 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. © 2018 Pearson Education, Inc. 24.2 Gastrointestinal Microbiota • Summary of the Gut Microbiota: The Two Major Components • The vast majority (~98 percent) of all human gut phylotypes fall into one of three major bacterial phyla: Firmicutes (gram +, Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus), Bacteroidetes (gram -, can degrade complex plant carbohydrates), and Proteobacteria (gram -, E. coli, Pseudomonas-). • Individuals may have mostly Firmicutes, mostly Bacteriodetes (Bacteroides and Prevotella) , or a mix of the two. This may regulate metabolism and the host’s propensity for obesity. © 2018 Pearson Education, Inc. 24.2 Gastrointestinal Microbiota • Gut Enterotypes • 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, and #3 is enriched in Ruminococcus. • Early studies indicate that each enterotype is functionally as well as phylogenetically distinct. © 2018 Pearson Education, Inc. Gut microbiomes are diet driven © 2018 Pearson Education, Inc. The balance between metabolically healthy microbiota and dysbiosis is crucial Fan, Y., Pedersen, O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 19, 55–71 (2021). https://doi.org/10.1038/s41579020-0433-9 © 2018 Pearson Education, Inc. 24.6 Human Study Groups and Animal Models • Mouse Models • Mice have a short life cycle and well-defined genetic lines; they can be raised in a germ-free environment. • antibiotic therapy • strict dietary control • fecal transplants • germ-free environment © 2018 Pearson Education, Inc. 24.8 Disorders Attributed to the Gut Microbiota • The Role of the Gut Microbiota in Obesity: Mouse Models • 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. © 2018 Pearson Education, Inc. Obese mice have more methanogens methanogens Acetate, proprionate and butyrate © 2018 Pearson Education, Inc. Figure 24.19 24.8 Disorders Attributed to the Gut Microbiota • The Gut Microbiota and Human Obesity • Like the mouse model, obese humans have more Firmicutes and methanogens than non-obese humans. • The nature and transferability of gut microbiota is dependent on diet as well genetics. © 2018 Pearson Education, Inc. Transfer of obese condition by fecal transplant. Transplanting fecal material from the gut contents of pair identical human twin study group to germ free mice showed that the obese twin microbiota made the mouse obese. © 2018 Pearson Education, Inc. The gut-brain axis. The influence of gut microbiota on behaviour- particularly autism. MIA= maternal immune activation—autism-like behaviours– shift in the composition of gut bacteria Bacteroides fragilis displaces 4-ethylphenylsulfate producers and return gut chemistry to normal. Epidemiological evidence implicates maternal infection as a risk factor for autism spectrum disorder and schizophrenia. Animal models corroborate this link and demonstrate that maternal immune activation (MIA) alone is sufficient to impart lifelong neuropathology and altered behaviors in offspring. © 2018 Pearson Education, Inc. Causes anxiety like behaviour Oral Microflora • Metagenomic analysis of human microflora shows a complex microbial community • Most microorganisms are facultatively aerobic • Some are obligately anaerobic or obligately aerobic • Firmicutes are most abundant • Veillonella parvula is most abundant single species • Streptococcus is most abundant genus • Comprises ~25% of bacteria in some individuals © 2018 Pearson Education, Inc. © 2018 Pearson Education, Inc. Figure 1 Study design and top 15 abundant genera of the oral microbiota and probiotic yoghurt. (A) Samples of both members of recruited couples were collected of the anterior dorsal tongue surface and saliva prior to (blue) and after an intimate kiss of 10 s (red). One of the partners was asked to consume 50 ml of a probiotic yoghurt drink, and again tongue and saliva were collected of the donator prior to (yellow) and the receiver after a second intimate kiss (green). (B) Relative abundances of the top 15 most dominant genera of the oral microbiota and probiotic yoghurt plotted on a log transformed color-coded rainbow scale from 0 to 12 from black, blue, green, yellow, orange to red. Headers include partner, probiotic yoghurt drink, saliva, tongue, sample IDs, couples, and sample type, as indicated by the same color-coding in the study design. © 2018 Pearson Education, Inc. Conclusions This study indicates that a shared salivary microbiota requires a frequent and recent bacterial exchange and is most pronounced in couples with relatively high intimate kiss frequencies of at least nine intimate kisses per day or in couples sampled no longer than 1.5 h after the latest kiss. The microbiota on the dorsal surface of the tongue is more similar among partners than unrelated individuals, but its similarity does not clearly correlate to kissing behavior. Our findings suggest that the shared microbiota among partners is able to proliferate in the oral cavity, but the collective bacteria in the saliva are only transiently present and eventually washed out, while those on the tongue’s surface found a true niche, allowing long-term colonization. © 2018 Pearson Education, Inc.