The Human Microbiome, Diet, and Health Workshop Summary (2013) / Chapter Skim
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2 Study of the Human Microbiome
2 Study of the Human Microbiome
Pages 33-54
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From page 33... ...
Much of this interest has been driven by and directed toward genomics, with a major goal of the Human Microbiome Project (HMP) being to characterize the genomic makeup of all microbes inhabiting the human body.
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The "healthy cohort" project is a sequencing study of the microbiome based on sampling from 5 major body sites (18 subsites) : nasal passages, oral cavities, skin, gastrointestinal (GI)
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. Additionally, the project is accumulating clinical and phenotype data associated with either the healthy cohort sequencing data or sequencing data from the demonstration projects and is planning to collect nucleic acid extracts and, potentially, cell lines from the healthy cohort.
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. She said, "The human microbiome is probably like a lot of other microbial ecosystems out there on the planet." However, while 16S rRNA data show that microbial composition varies among body sites and even within body sites between individuals, metagenomic data indicate that the major microbial metabolic pathways are effectively the same across body sites.
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With respect to the notion of a core microbiome, although reproducible subsets of microbes may be found in all indi idualsv at grosser taxonomic levels, such as the phylum level (Backhed et al., 2005) and perhaps at the genus level for some body sites (e.g., the skin and possibly the vaginal microbiomes)
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(2011) calculated rates of horizontal gene transfer among more than 2,000 bacterial genomes and reported a greater frequency of horizontal gene transfer in the human microbiome than in other environments, with the most transfer occurring among microbes inhabiting the same body sites (e.g., the microbes of two gut microbial communities are more likely to engage in horizontal gene transfer than a gut microbe and a skin microbe)
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The use of microbiome signatures as biomarkers for disease presence; 2. The use of enterotypes to classify individuals by disease risk or pharmacokinetics; 3.
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By comparing specific sequence reads to sequences with known functions, they can infer function. 13 HMP researchers are sequencing as many microbiome reference genomes as possible as part of the "healthy cohort" study that Lita Proctor described (see previous section for a summary of her presentation)
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The researchers detected a very clear signal that people with colorectal cancer have an enrichment of Fusobacteria in their tumor tissue. As a final example, HMP researchers used both reference-based and de novo OTU classification to analyze OTU data from all five major body sites among the "healthy cohort" study individuals.
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"If there is such a thing as a core microbiome," Wortman said, "it may be at the level of function more than at the level of organism." Challenges Wortman identified five major challenges to HMP data interpretation: 1. Meeting data volume and computational requirements.
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From page 43... ...
, across both time and space? "This is really quite a tough problem," Nicholson said, "probably the toughest problem in 21st-century biology." The Metabolic Window on Complex System Activity Complex interactions between the microbiome and its host generate more than differential disease risks.
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(See the summary of Ellen Silbergeld's presentation in Chapter 5 for a more detailed discussion of the impact of horizontal gene transfer on the microbiome.) • hat are they doing (besides digesting seaweed)
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Microbial co-metabolism of bile acids also impacts lipid bioavailability. Modifying Host-Microbiome Metabolic Interactions: Mouse and Rat Models When thinking about how the gut microbiome impacts human metabolism, the tendency is to think about distal colon processing and the production of short-chain fatty acids, but the microbiome plays an important role in the upper gut as well -- for example, with lipid bioavailability.
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. Another body of evidence indicating that the microbiome plays a key role in human metabolism comes from research on bariatric surgery in both animal models and humans.
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Population Metabolic Phenotyping and Disease Risk In addition to its potential role in personalized medicine, metabolic phenotyping has potential applicability at the population level. Holmes et al.
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For example, there was a question about the implications of studying the impact of bariatric surgery on bile salt metabolism in rats, given that rats do not have a gall bladder and that human patients that undergo bariatric surgery have an increased incidence of gall bladder disease. Nicholson responded, "The important thing about these rat and mouse models is they help you to develop the tools for studying these complex interactions.
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Yet, they induce huge metabolic changes. He said, "I think data already exist that probiotics and prebiotics change the existing microbiome function." Proctor agreed that inducing a biological change does not require a change in microbiome composition.
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2009. Bacterial community variation in human body habitats across space and time.
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2008a. Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model.
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2010. A human gut microbial gene catalogue established by metagenomic sequencing.
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Nature Reviews Microbiology 9(4)
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2011. Systemic gut microbial modulation of bile acid metabolism in host tissue compartments.
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