Ending the War Metaphor The Changing Agenda for Unraveling the Host-Microbe Relationship: Workshop Summary (2006) / Chapter Skim
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1 Microbial Communities of the Gut
1 Microbial Communities of the Gut
Pages 35-79
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From page 35... ...
(2005) state in their contribution to this chapter, "It seems appropriate to view ourselves as a composite of many species and our genetic landscape as an amalgam of genes embedded in our Homo sapiens genome and in the genomes of our affiliated microbial partners." The first paper in this chapter, contributed by workshop presenter Karen Guillemin, focuses on the establishment of the gut microbiota (in humans, during the early days of infancy)
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From page 36... ...
He and coworkers review current knowledge of the structure and function of the human gut microbiota, as well as recent research that reveals coevolution between humans and gut microbes to their mutual benefit. Over the course of evolution, symbiotic gut bacteria have become, in Gordon's words, "master physiological chemists," employing a broad range of strategies to manipulate host genomes.
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. The embryos hatch out of their eggshells between 2 and 3 dpf, prior to the completion of gut maturation.
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Acquisition of this microbiota happens concurrently with the later events of gut maturation; a similar process of postnatal gut maturation occurs in mammals as they acquire their microflora. Role of the Microbiota in Gut Development and Function To examine the functional significance of the temporal relationship between microbiota establishment and gut maturation, we turned to gnotobiology, the use of GF animals (see subsequent paper by Bäckhed et al.)
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Alkaline phosphatase activity was restored to control levels in GF animals that were exposed, 5 dpf, to bacteria from their siblings. Another marker of maturation we examined was glycan expression.
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Conclusion Our findings on the role of the microbiota in the development of the GI tract in zebrafish show this to be a promising model for investigating the role of microbial communities in the developmental biology of the host. We have been able to show that the microbiota is required for gut maturation -- as indicated by patterns of expression of glycans, by alkaline phosphatase activity, and by goblet cell census -- and that the microbiota is important for such functions as protein absorption and GI motility.
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From page 41... ...
. Our gut microbiota can be pictured as a microbial organ placed within a host organ: It is composed of different cell lineages with a capacity to communicate with one another and the host; it consumes, stores, and redistributes energy; it mediates physiologically important chemical transformations; and it can maintain and repair itself through self replication.
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From page 42... ...
This review aims to illustrate these points and highlight some future challenges for the field. Microbial Diversity in the Human Gut Bioreactor The adult human gastrointestinal tract contains all three domains of life-bacteria, archaea, and eukarya.
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Although these values are somewhat arbitrary and the terms "genus" and "species" are not precisely defined for microbes, we use them here to frame a view of human gut microbial ecology. When the sequences (n = 495 greater than 900 base pairs)
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vulgatus human colon human colon human colon rat feces human colon [Prevotella] heparina [Prevotella]
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. Ratios are the number of sequences represented in the human gut relative to the total number in the subgroup; red, yellow, and black indicate majority, minority, and absence of sequences represented in human GI tract, respectively.
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The estimated 1,200 viral genotypes in human feces (Breitbart et al., 2003) suggest that a phage attack is a powerful shaper of the gut's microbial genetic landscape (Fuhrman, 1999; Winter et al., 2004)
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. These findings provide insights about how functional diversity and adaptability are achieved by a prominent member of the human colonic microbiota (Figure 1-4)
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Microbial fermentation of otherwise indigestible polysaccharides in these platforms is made possible by induced expression of substrate-appropriate sets of bacterial polysaccharide-binding proteins and glycoside hydrolases.
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thetaiotaomicron, impart stability to the gut ecosystem by having the capacity to turn to host polysaccharides when dietary polysaccharides become scarce. The highly variable outer chain structures of mucus and epithelial cell surface glycans are influenced by host genotype and by microbial regulation of host glycosyltransferase gene expression.
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. This observation might seem paradoxical at first but can be explained by the fact that the gut microbiota allows energy to be salvaged from otherwise indigestible dietary polysaccharides (Yamanaka et al., 1977)
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Defining the representation of mesophilic methanogens in the colonic microbiota of individuals, sequencing their genomes [as we are currently doing with Methanobrevibacter smithii, a prevalent isolate from the human colon (Miller and Wolin, 1982)
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Finally, just as microbiotas have coevolved with their animal hosts, this field must coevolve with its academic hosts and their ability to devise innovative ways of assembling interactive interdisciplinary research groups necessary to advance our understanding. ACTIVITIES OF HUMAN COLONIC MICROBES Abigail A
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From page 53... ...
For example, the small intestine is designed to promote a fast flow of contents, a feature that has the effect of discouraging microbial growth by washing microbes through before they can establish themselves. The flow of contents through the colon, by contrast, is so slow that microbes can easily establish themselves and reach concentrations that are high enough to make up at least 30 percent of human colonic contents (Figure 1-5)
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From page 54... ...
A striking feature of the colonic microflora is that the majority of colonic bacteria are gram-positive bacteria, virtually all of which are obligate anaerobes (Bäckhed et al., 2005; Salyers, 1986; Salyers and Shipman, 2002; Wilson and Blitchington, 1996)
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From page 55... ...
Because the human colon is not as accessible to sampling as other areas of the human body, mice -- or some other animal such as the pig -- will have to be accepted as models for colonic populations if progress in understanding niches in the colon is to be made. As has already been mentioned, gram-positive bacteria account for at least 65 percent of colonic isolates.
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From page 56... ...
These bacteria may receive more attention in the future due to interest in the possibility that the colonic microflora play a role in inflammatory bowel disease and colon cancer. The preponderance of these previously unknown gram-positive bacteria in the normal human colon raises an interesting practical question.
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Nutritional Interactions The colon has been called a second organ of digestion because dietary material that is not digested in the small intestine by human enzymes is fermented by the colonic microflora to produce short-chain fatty acids such as acetate, propionate, and butyrate (Bäckhed et al., 2005; Salyers, 1986; Salyers and Shipman,
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Possible Detoxifying Activities of the Human Colonic Microflora Another interesting example of a beneficial interaction between cows and bacteria comes from scientists who were trying to solve the problem of animals in Australia and many tropical and subtropical countries that cope with toxic plants. The main toxin is mimosine, a plant compound that can kill a ruminant.
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From page 59... ...
For this reason, toxic substances in the diet are likely to have a disproportionate effect on colonic mucosal cells or on cells they encounter if they are absorbed. Looming behind interest in this topic is the question of whether colon cancer risk might be affected, positively or negatively, by activities of the colonic microflora.
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The concern is that antibioticresistant bacteria that arise due to selection from the use of antibiotics as prophylactic treatments or as feed additives are moving through the food supply and into the human intestinal tract, where the resistance genes could be transferred to bacteria that permanently or temporarily reside in the human colon. How important this process is for the development of resistance in bacteria -- that are serious causes of human infections -- has not been conclusively established, but it remains a concern.
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From page 61... ...
This discussion has surveyed briefly some of the issues that have been raised in connection with the normal microflora of the human colon and its possible role, if it becomes unbalanced, in human disease. A theme that has run through this article is the surprising lack of information about some very basic aspects of the human microflora.
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From page 62... ...
This means that the microfloras of mammalian bodies have fallen into a funding vacuum unless they can be tied to disease. No one questions the importance of studies on inflammatory bowel disease or colon cancer, but without a normal baseline or criterion for how external factors such as diet might affect this baseline, modern studies of these diseases are likely to fall to the same fate that was previously met by the cultivation-based studies: studies whose results contradict each other because they lack any consensus as to what is normal and what amount of variation can be counted as significant.
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MICROBIAL COMMUNITIES OF THE GUT 63 ANNEX 1-1 TABLE 1-1 Comparison of the Glycoside Hydrolase and Polysaccharide Lyases in the Human, Mouse, and B thetaiotaomicron Genomes Glycoside Hydrolase (GH)
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64 ENDING THE WAR METAPHOR TABLE 1-1 Continued Glycoside Hydrolase (GH) or Polysaccharide Lyase (PL)
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MICROBIAL COMMUNITIES OF THE GUT 65 TABLE 1-1 Continued Glycoside Hydrolase (GH) or Polysaccharide Lyase (PL)
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66 ENDING THE WAR METAPHOR TABLE 1-1 Continued Glycoside Hydrolase (GH) or Polysaccharide Lyase (PL)
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MICROBIAL COMMUNITIES OF THE GUT 67 TABLE 1-1 Continued Glycoside Hydrolase (GH) or Polysaccharide Lyase (PL)
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68 ENDING THE WAR METAPHOR TABLE 1-1 Continued Glycoside Hydrolase (GH) or Polysaccharide Lyase (PL)
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gut motility comparisons of the enteric nervous system in GF versus CONV-R animals are needed; potential implications concerning the pathogenesis of irritable bowel syndrome in humans GF rats have Impaired excretion of bile acids (Gustafsson et al., reduced 1966) bile acid deconjugation GF rats This effect, together with deconjugation defect, (Wostmann, 1973)
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sensitive than restriction need to be delineated CONV-R animals GF mice have Associated with reduced fat stores (Bäckhed et al., lower circulating 2004; Bäckhed and levels of leptin Gordon, and adiponectin unpublished observation) Nutrition/metabolism GF mice are The gut microbiota produces vitamin K, B6, B12, (Gustafsson et al., vulnerable to biotin, folic acid, and pantothenate 1962; Sumi vitamin et al., 1977; deficiencies Wostmann et al., 1963)
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Levenson et al., 1969; Wostmann et al., 1982, 1968) GF mice absorb GF mice have large bile acid pools (Gustaffsson et al., more cholesterol 1975)
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some mouse models GF mice Mechanism to be defined; potential implications for (Matsuzawa, 1965) are more ameliorating GI syndrome in patients receiving radioresistant radiotherapy for abdominal/pelvic malignancies SOURCE: Bäckhed et al.
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2002. Microbial community structure and activity in a compartmentalized, anaerobic bioreactor.
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Applied Environmental Microbiology 68(6)
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C Presentation at the Forum on Microbial Threats Workshop Ending the War Metaphor: The Changing Agenda for Unraveling the Host-Microbe Relationship.
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Applied Environmental Microbiology 69(6)
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Presentation at the Forum on Microbial Threats Workshop Ending the War Metaphor: The Changing Agenda for Unraveling the Host-Microbe Relationship, Washington, D.C., Institute of Medicine, Forum on Microbial Threats. Salyers AA, Shipman JA.
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2004. Human intestinal bacteria as reservoirs for antibiotic resistance genes.
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1996. Human colonic biota studied by ribosomal DNA sequence analysis.
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