Recommended Readings: Rob Knight, Ph.D. Wednesday, Oct. 30, 2013

Wednesday, October 30, 2013
4:00 p.m., Carson Family Auditorium

Rob Knight, Ph.D.
HHMI Early Career Scientist and Professor
Department of Chemistry & Biochemistry, Department of Computer Science, and BioFrontiers Institute
University of Colorado at Boulder

Gut Microbes and their Role in Malnutrition and Obesity

Recommended Readings:

Review Papers

Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012). The impact of the gut microbiota on human health: an integrative view. Cell, 148(6), 1258–1270. doi:10.1016/j.cell.2012.01.035

Gevers, D., Knight, R., Petrosino, J. F., Huang, K., McGuire, A. L., Birren, B. W., … Huttenhower, C. (2012). The Human Microbiome Project: a community resource for the healthy human microbiome. PLoS Biology, 10(8), e1001377. doi:10.1371/journal.pbio.1001377

Hamady, M., & Knight, R. (2009). Microbial community profiling for human microbiome projects : Tools , techniques , and challenges, Genome Research, 19(7), 1141–1152. doi:10.1101/gr.085464.108.19

Ley, R. E., Lozupone, C. a, Hamady, M., Knight, R., & Gordon, J. I. (2008). Worlds within worlds: evolution of the vertebrate gut microbiotaNature Reviews Microbiology6(10), 776–788. doi:10.1038/nrmicro1978

Empirical Articles

Costello, E., Lauber, C., & Hamady, M. (2009). Bacterial community variation in human body habitats across space and time. Science, 326, 8–11.

The Human Microbiome Project Consortium. (2012). Structure, function and diversity of the healthy human microbiome. Nature, 486(7402), 207–14. doi:10.1038/nature11234

Ley, R. E., Bäckhed, F., Turnbaugh, P., Lozupone, C. A, Knight, R. D., & Gordon, J. I. (2005). Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences of the United States of America, 102(31), 11070–5. doi:10.1073/pnas.0504978102

Lozupone, C. A., Stombaugh, J., Gonzalez, A., Ackermann, G., Jansson, J. K., Gordon, J. I., … Knight, R. (2013). Meta-analyses of studies of the human microbiota, Genome Research, 23,1704–1714. doi:10.1101/gr.151803.112

Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., … Gordon, J. I. (2009). A core gut microbiome in obese and lean twins. Nature, 457(7228), 480–484. doi:10.1038/nature07540

Turnbaugh, P. J., Ley, R. E., Mahowald, M. a, Magrini, V., Mardis, E. R., & Gordon, J. I. (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122), 1027–31. doi:10.1038/nature05414

Yatsunenko, T., Rey, F. E., Manary, M. J., Trehan, I., Dominguez-Bello, M. G., Contreras, M., … Gordon, J. I. (2012). Human gut microbiome viewed across age and geography. Nature, 486(7402), 222–7. doi:10.1038/nature11053

Roles of Microorganisms in Diseases Uncovered

In a variety of today’s headlines in the world of science and medicine, the ubiquitous bacteria warrant special mention.  In our last blog posting, we described the alarming concern over antibiotic resistance.  Today, current information provides us with on an overarching view of some ethics and social implications of the Human MicrobiomeProject, and then we drill down into the details of some recent microbiological discoveries that have been reported in the scientific literature.
On Friday, September 19, a regarded online publication named GenomeWeb Daily News reported that the National Institutes of Health plan to address the ethical, legaland social implications of the Human Microbiome Project (HMP).  A brief definition of the project can be found here.  In essence, HMP is proposed as a feasibility study with “the goal of identifying and characterizing the microorganisms which are found in association with both healthy and diseased humans” (from
Social and ethical questions surround HMP which include questions about potential clinical applications of this research, the implications for health and for society, and privacy concerns for groups, individuals and families associated with the research.  It’s important that these aspects are studied by the NIH and three awards of hundreds of thousands of dollars are available over the three-year timetable for this project.

Enter the lowly bacterium…
Several scientific headlines have been snatched by bacteria during the past couple of days.  The first article of note also gives credit to the eukaryotic Candida albicans, where researchers from Beth Israel Deaconess Medical Center, Boston, and Harvard Medical School, Boston describe prokaryotic-eukaryotic interactions of Acinetobacter baumannii and C. albicans as identified using the common nematode Caenorhabditis elegans.  A paucity of data exists on the bacterial-fungal encounters within a living host and in this study, A. baumannii inhibited virulence of C. albicans.  This in vivo work supports existing in vitro studies.  The study provides a whole-animal model to open the door to investigating the dynamics of polymicrobial infections.
Another study reported in the October issue of the Journal of Medical Microbiology received recognition  today when several articles described the interactions of the gut bacterium Enterococcus faecalis and colon cells (Medical News Today, September 22, 2008, “Gut Bacterium Linked to Colon Cancer”,, ScienceDaily, September 22, 2008, “Cancer-causing Gut Bacteria Exposed”,, Allen, T.D., et al., 2008.  Dichotomous metabolsim of Enterococcus faecalis induced by haematin starvation modulates colonic gene expression.  J Med Microbiol 57:1193-1204.)  This bacterium can survive using respiration or fermantation, and when it relies on the latter metabolic processes it releases superoxide, which leads to signalling in macrophages.  Superoxide also increades the productivity of genes that are associated with cancer.
In another host/bacterium study, investigators at the University of Chicago and Yale University demonstrated that when mice were exposed to some forms of bacteria the onset of Type I diabetes may be prevented by upsetting this autoimmune disease.  In a paper published in Nature, Li Wen at Yale and Alexander V. Chervonsky at the University of Chicago demonstrated that non-obese diabetic (NOD) mice were significantly less likely to develop diabetes when exposed to harmless gut bacteria.  Understanding the balance of the bacterial / disease interaction is important for understanding the underlying basis for the disease.
Initiatives to better understand the Human Microbiome and studies that publish data to help understand disease / bacterial interactions move us closer to understanding our links with the microbiological world.  The use of probiotics has been suggested in the popular press for establishing healthy microflora.  Now, we may be more dependent upon our microflora for good health than we ever thought imagineable in the past.