The human microbiome: at the interface of health and disease - Nature Reviews Genetics
- ️Blaser, Martin J.
- ️Tue Mar 13 2012
Baumann, P. & Moran, N. A. Non-cultivable microorganisms from symbiotic associations of insects and other hosts. Antonie van Leeuwenhoek 72, 39–48 (1997).
Turnbaugh, P. J. et al. The Human Microbiome Project. Nature 449, 804–810 (2007).
Ehrlich, S. D. Metagenomics of the Human Body (ed. Nelson, K. E.) 307–316 (Springer, 2011).
Ravel, J. et al. Vaginal microbiome of reproductive-age women. Proc. Natl Acad. Sci. USA 108, 4680–4687 (2011). This study describes vaginal microbiome differences and similarities in women of reproductive age who vary by ethnicity, and explores factors that are related to bacterial vaginosis.
Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011). This paper proposes enterotype classifications that are defined by the intrinsic characteristics of the gut microbiome, and that seem to be independent of ethnic or dietary factors.
Morris, S. C. & Peel, J. S. The earliest annelids: lower Cambrian polychaetes from the Sirius Passet Lagerstatte, Peary Land, North Greenland. Acta Palaeontol. Pol. 53, 135–146 (2008).
Ley, R., Lozupone, C. A., Hamady, M., Knight, R. & Gordon, J. Worlds within worlds: evolution of the vertebrate gut microbiota. Nature Rev. Microbiol. 6, 776–788 (2008). A review that contrasts the microbial communities in the vertebrate gut with each other and with free-living microbial communities.
Ochman, H. et al. Evolutionary relationships of wild hominids recapitulated by gut microbial communities. PLoS Biol. 8, e1000546 (2010).
Moran, N. A., Munson, M. A., Baumann, P. & Ishikawa, H. A Molecular clock in endosymbiotic bacteria is calibrated using the insect hosts. Proc. R. Soc. Lond. B 253, 167–171 (1993).
Benson, A. K. et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc. Natl Acad. Sci. USA 107, 18933–18938 (2010).
Wikoff, W. R. et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl Acad. Sci. USA 106, 3698–3703 (2009). A comparison of germ-free and normal animals, which shows that the microbiome has substantial effects on host blood metabolites, including on the metabolism of amino acids and organic acids.
Petchey, O. L., Eklof, A., Borrvall, C. & Ebenman, B. Trophically unique species are vulnerable to cascading extinction. Am. Nat. 171, 568–579 (2008).
Blaser, M. J. & Kirschner, D. The equilibria that allow bacterial persistence in human hosts. Nature 449, 843–849 (2007). The authors of this paper propose that co-evolved bacteria in human hosts establish homeostases that conform to the principles of Nash equilibria. Understanding such equilibria may provide insight into shifts in microbial communities in health and disease.
Maynard Smith, J. Models in Ecology. (Cambridge Univ. Press, UK, 1974).
Blaser, M. J. Who are we? Indigenous microbes and the ecology of human diseases. EMBO Rep. 7, 956–960 (2006).
Tringe, S. G. et al. Comparative metagenomics of microbial communities. Science 308, 554–557 (2005).
Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006). A seminal paper describing the ability of the gut microbiome to extract energy from dietary sources.
Warnecke, F. et al. Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite. Nature 450, 560–565 (2007).
Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010). The authors report the identification of a library of microbial genes that are found in the human gut microbiome using high-throughput metagenomic sequencing.
Nelson, K. E. et al. A catalog of reference genomes from the human microbiome. Science 328, 994–999 (2010).
Kuczynski, J. et al. Experimental and analytical tools for studying the human microbiome. Nature Rev. Genet. 13, 47–58 (2012).
Greenblum, S., Turnbaugh, P. J. & Borenstein, E. Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease. Proc. Natl Acad. Sci. USA 109, 594–599 (2012). A new method of comparing metagenomic data that involves analysing metabolic networks and their associated genes to describe changes that occur in disease (such as in obesity or IBD).
Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).
Bogaert, D. et al. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PLoS ONE 6, e17035 (2011).
Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009). This study describes temporal and topographical variations in the human microbiome at various anatomical sites.
Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011).
Kuczynski, J. et al. Direct sequencing of the human microbiome readily reveals community differences. Genome Biol. 11, 210 (2010).
Dethlefsen, L. & Relman, D. A. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl Acad. Sci. USA 108, 4554–4561 (2011). This paper describes the substantial alterations that occur in the gut microbiome after exposure to antibiotics. It also highlights varied taxonomic changes among individuals.
Dethlefsen, L., Huse, S., Sogin, M. L. & Relman, D. A. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 6, e280 (2008).
Huse, S. M. et al. Exploring microbial diversity and taxonomy using SSU rRNA hypervariable tag sequencing. PLoS Genet. 4, e1000255 (2008).
Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl Acad. Sci. USA 102, 11070–11075 (2005).
Linz, B. et al. An African origin for the intimate association between humans and Helicobacter pylori. Nature 445, 915–918 (2007).
Douglass, J. M., Li, Y. & Tinanoff, N. Association of mutans streptococci between caregivers and their children. Pediatr. Dent. 30, 375–387 (2008).
Li, Y., Ismail, A. I., Ge, Y., Tellez, M. & Sohn, W. Similarity of bacterial populations in saliva from African-American mother-child dyads. J. Clin. Microbiol. 45, 3082–3085 (2007).
Li, M. et al. Symbiotic gut microbes modulate human metabolic phenotypes. Proc. Natl Acad. Sci. USA 105, 2117–2122 (2008).
McNulty, N. P. et al. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Sci. Transl. Med. 3, 106ra106 (2011).
Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).
Fierer, N., Hamady, M., Lauber, C. L. & Knight, R. The influence of sex, handedness, and washing on the diversity of hand surface bacteria. Proc. Natl Acad. Sci. USA 105, 17994–17999 (2008).
Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A. & Brown, P. O. Development of the human infant intestinal microbiota. PLoS Biol. 5, e177 (2007). This study describes the taxonomic developments that occur in the infant microbiome and the relationships between these changes and environmental exposures.
Blaser, M. J. & Falkow, S. What are the consequences of the disappearing human microbiota? Nature Rev. Microbiol. 7, 887–894 (2009). This article proposes that our modern lifestyle has led to the extinction of certain microbes, and that their disappearance may have deleterious effects on human health.
Sjolund, M., Wreiber, K., Andersson, D. I., Blaser, M. J. & Engstrand, L. Long-term persistence of resistant Enterococcus species after antibiotics to eradicate Helicobacter pylori. Ann. Intern. Med. 139, 483–487 (2003).
Blaser, M. J. Antibiotic overuse: stop the killing of beneficial bacteria. Nature 476, 393–394 (2011).
Evans, A. S. Causation and disease: the Henle–Koch postulates revisited. Yale J. Biol. Med. 49, 175–195 (1976).
Muegge, B. D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332, 970–974 (2011).
Huston, M. A. Biological Diversity: The Coexistence Of Species On Changing Landscapes (Cambridge Univ. Press, UK, 1994).
Kennedy, T. A. et al. Biodiversity as a barrier to ecological invasion. Nature 417, 636–638 (2002).
Strogatz, S. H. Exploring complex networks. Nature 410, 268–276 (2001).
Paine, R. T. Food web complexity and species diversity. Am. Nat. 100, 65–75 (1966).
Sole, R. V. & Montoya, J. M. Complexity and fragility in ecological networks. Proc. Biol. Sci. 268, 2039–2045 (2001).
Borrvall, C. & Ebenman, B. Early onset of secondary extinctions in ecological communities following the loss of top predators. Ecol. Lett. 9, 435–442 (2006).
Bik, E. M. et al. Molecular analysis of the bacterial microbiota in the human stomach. Proc. Natl Acad. Sci. USA 103, 732–737 (2006).
Maldonado-Contreras, A. et al. Structure of the human gastric bacterial community in relation to Helicobacter pylori status. ISME J. 5, 574–579 (2011).
Li, Y., Caufield, P. W., Dasanayake, A. P., Wiener, H. W. & Vermund, S. H. Mode of delivery and other maternal factors influence the acquisition of Streptococcus mutans in infants. J. Dent. Res. 84, 806–811 (2005).
Dominguez-Bello, M. G. et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl Acad. Sci. USA 107, 11971–11975 (2010). This study shows that infants have largely undifferentiated microbiota across multiple anatomic sites immediately after birth, and that delivery mode determines which types of bacteria of the infant microbiome are the earliest colonizers.
Savage, D. C., Dubos, R. & Schaedler, R. W. The gastrointestinal epithelium and its autochthonous bacterial flora. J. Exp. Med. 127, 67–76 (1968). One of the pioneering studies of the features of the bacterial colonization of the gastrointestinal tract that occurs in early life.
Gronlund, M. M., Lehtonen, O. P., Eerola, E. & Kero, P. Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J. Pediatr. Gastroenterol. Nutr. 28, 19–25 (1999).
Grant, B. R. & Grat, P. R. Cultural inheritance of song and its role in the evolution of Darwin's finches. Evolution 50, 2471–2487 (1996).
Hunt, J. & Simmons, L. W. Maternal and paternal effects on offspring phenotype in the dung beetle Onthophagus taurus. Evolution 54, 936–941 (2000).
Raymond, J. et al. Genetic and transmission analysis of Helicobacter pylori strains within a family. Emerg. Infect. Dis. 10, 1816–1821 (2004).
Smillie, C. S. et al. Ecology drives a global network of gene exchange connecting the human microbiome. Nature 480, 241–244 (2011). The discovery of a large network of gene exchange that occurs in microbial communities and that allows rapid genetic information transfer to occur in the microbiome. The authors speculate that such networks have roles in specific human diseases.
Wirth, T. et al. Distinguishing human ethnic groups by means of sequences from Helicobacter pylori: lessons from Ladakh. Proc. Natl Acad. Sci. USA 101, 4746–4751 (2004).
Sharon, G. et al. Commensal bacteria play a role in mating preference of Drosophila melanogaster. Proc. Natl Acad. Sci. USA 107, 20051–20056 (2010).
Leyden, J. J., McGinley, K. J., Holzle, E., Labows, J. N. & Kligman, A. M. The microbiology of the human axilla and its relationship to axillary odor. J. Invest. Dermatol. 77, 413–416 (1981).
Dobzhansky, T. Further data on the variation of the Y chromosome in Drosophila pseudoobscura. Genetics 22, 340–346 (1937).
Mayr, E. Systematics And The Origin Of Species From The Viewpoint Of A Zoologist (Columbia Univ. Press, New York, USA, 1942).
Brailsford, S. R. et al. The microflora of the erupting first permanent molar. Caries Res. 39, 78–84 (2005).
Cephas, K. D. et al. Comparative analysis of salivary bacterial microbiome diversity in edentulous infants and their mothers or primary care givers using pyrosequencing. PLoS ONE 6, e23503 (2011).
Schaedler, R. W. The relationshp between the host and its intestinal microflora. Proc. Nutr. Soc. 32, 41–47 (1973).
Jukes, T. H. Antibiotics in feeds. Science 204, 8 (1979).
Robinson, C. J. & Young, V. B. Antibiotic administration alters the community structure of the gastrointestinal micobiota. Gut Microbes 1, 279–284 (2010).
Wlodarska, M. et al. Antibiotic treatment alters the colonic mucus layer and predisposes the host to exacerbated Citrobacter rodentium-induced colitis. Infect. Immun. 79, 1536–1545 (2011).
Gemmell, N. J. & Slate, J. Heterozygote advantage for fecundity. PLoS ONE 1, e125 (2006).
Cauci, S. et al. Prevalence of bacterial vaginosis and vaginal flora changes in peri- and postmenopausal women. J. Clin. Microbiol. 40, 2147–2152 (2002).
Osborne, N. G., Wright, R. C. & Grubin, L. Genital bacteriology: a comparative study of premenopausal women with postmenopausal women. Am. J. Obstet. Gynecol. 135, 195–198 (1979).
Peek, R. M. Jr & Blaser, M. J. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nature Rev. Cancer 2, 28–37 (2002).
Giannakis, M., Chen, S. L., Karam, S. M., Engstrand, L. & Gordon, J. I. Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc. Natl Acad. Sci. USA 105, 4358–4363 (2008).
Li, X. X. et al. Bacterial microbiota profiling in gastritis without Helicobacter pylori infection or non-steroidal anti-inflammatory drug use. PLoS ONE 4, e7985 (2009).
Mariat, D. et al. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol. 9, 123 (2009).
Nordling, C. O. A new theory on cancer-inducing mechanism. Br. J. Cancer 7, 68–72 (1953).
Vanhoutvin, S. A. et al. Butyrate-induced transcriptional changes in human colonic mucosa. PLoS ONE 4, e6759 (2009).
Hamilton, W. D. The moulding of senescence by natural selection. J. Theor. Biol. 12, 12–45 (1966). A pioneering paper that describes how several key factors (fertility, mortality and age) affect population dynamics.
Perry, S. et al. Infection with Helicobacter pylori is associated with protection against tuberculosis. PLoS ONE 5, e8804 (2010).
Higgins, P. D. et al. Prior Helicobacter pylori infection ameliorates Salmonella typhimurium-induced colitis: mucosal crosstalk between stomach and distal intestine. Inflamm. Bowel Dis. 17, 1398–1408 (2011).
Arnold, I. C. et al. Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells. J. Clin. Invest. 121, 3088–3093 (2011).
Atherton, J. C. & Blaser, M. J. Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J. Clin. Invest. 119, 2475–2487 (2009).
Blaser, M. J. & Webb, G. Host demise as a beneficial function of indigenous microbiota in multicellular hosts. in Am. Soc. Microbiol. Conf. Beneficial Microbes (Lake Tahoe, Nevada, USA, 2005).
Patel, R. V. & Lebwohl, M. Psoriasis. Ann. Intern. Med. 155, ITC2-1 (2011).
Gao, Z., Tseng, C. H., Strober, B. E., Pei, Z. & Blaser, M. J. Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLoS ONE 3, e2719 (2008).
Grice, E. A. & Segre, J. A. The skin microbiome. Nature Rev. Microbiol. 9, 244–253 (2011). A comprehensive review of the skin microbiome and its connection to several diseases.
McDowell, A. et al. A novel multilocus sequence typing scheme for the opportunistic pathogen Propionibacterium acnes and characterization of type I cell surface-associated antigens. Microbiology 157, 1990–2003 (2011).
Price, L. B. et al. Community analysis of chronic wound bacteria using 16S rRNA gene-based pyrosequencing: impact of diabetes and antibiotics on chronic wound microbiota. PLoS ONE 4, e6462 (2009).
Grice, E. A. et al. Longitudinal shift in diabetic wound microbiota correlates with prolonged skin defense response. Proc. Natl Acad. Sci. USA 107, 14799–1804 (2010).
Andersson, A. F. et al. Comparative analysis of human gut microbiota by barcoded pyrosequencing. PLoS ONE 3, e2836 (2008).
McColl, K. E. Helicobacter pylori infection. N. Engl. J. Med. 362, 1597–1604 (2010).
el-Serag, H. B. & Sonnenberg, A. Opposing time trends of peptic ulcer and reflux disease. Gut 43, 327–333 (1998).
Chen, Y. & Blaser, M. J. Inverse associations of Helicobacter pylori with asthma and allergy. Arch. Intern. Med. 167, 821–827 (2007).
Plottel, C. S. & Blaser, M. J. Microbiome and malignancy. Cell Host Microbe 10, 324–335 (2011).
Lazarova, D. L., Bordonaro, M., Carbone, R. & Sartorelli, A. C. Linear relationship between Wnt activity levels and apoptosis in colorectal carcinoma cells exposed to butyrate. Int. J. Cancer 110, 523–531 (2004).
Wu, S. et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nature Med. 15, 1016–1022 (2009).
Reikvam, D. H. et al. Depletion of murine intestinal microbiota: effects on gut mucosa and epithelial gene expression. PLoS ONE 6, e17996 (2011).
Castellarin, M. et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 22, 299–306 (2012).
Kostic, A. D. et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 22, 292–298 (2012).
Krisanaprakornkit, S. et al. Inducible expression of human β-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. Infect. Immun. 68, 2907–2915 (2000).
Littman, D. R. & Pamer, E. G. Role of the commensal microbiota in normal and pathogenic host immune responses. Cell Host Microbe 10, 311–323 (2011).
Ivanov, I. I. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4, 337–349 (2008). An important study that describes the immunological interplay between segmented filamentous bacteria and Th17 cells in the distal small bowel.
Round, J. L. & Mazmanian, S. K. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl Acad. Sci. USA 107, 12204–12209 (2010).
Ogura, Y. et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603–606 (2001).
Hugot, J. P. et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599–603 (2001).
Franchimont, D. et al. Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis. Gut 53, 987–992 (2004).
Ewaschuk, J. B., Tejpar, Q. Z., Soo, I., Madsen, K. & Fedorak, R. N. The role of antibiotic and probiotic therapies in current and future management of inflammatory bowel disease. Curr. Gastroenterol. Rep. 8, 486–498 (2006).
Hviid, A., Svanstrom, H. & Frisch, M. Antibiotic use and inflammatory bowel diseases in childhood. Gut 60, 49–54 (2011).
Manichanh, C. et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 55, 205–211 (2006).
Garrett, W. S. et al. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8, 292–300 (2010).
Lepage, P. et al. Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 141, 227–236 (2011).
Mondot, S. et al. Highlighting new phylogenetic specificities of Crohn's disease microbiota. Inflamm. Bowel Dis. 17, 185–192 (2011).
Abu-Shanab, A. & Quigley, E. M. The role of the gut microbiota in nonalcoholic fatty liver disease. Nature Rev. Gastroenterol. Hepatol. 7, 691–701 (2010).
Backhed, F., Manchester, J. K., Semenkovich, C. F. & Gordon, J. I. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Natl Acad. Sci. USA 104, 979–984 (2007).
Mutlu, E. et al. Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. Alcohol. Clin. Exp. Res. 33, 1836–1846 (2009).
Yan, A. W. et al. Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology 53, 96–105 (2011).
Fox, J. G. et al. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens. Gut 59, 88–97 (2010).
Chen, Y. et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54, 562–572 (2011).
Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).
Ajslev, T. A., Andersen, C. S., Gamborg, M., Sorensen, T. I. & Jess, T. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics. Int. J. Obes. 35, 522–529 (2011).
Luoto, R., Kalliomaki, M., Laitinen, K. & Isolauri, E. The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years. Int. J. Obes. 34, 1531–1537 (2010).
Li, J. V. et al. Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk. Gut 60, 1214–1223 (2011).
Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).
Scher, J. U. & Abramson, S. B. The microbiome and rheumatoid arthritis. Nature Rev. Rheumatol. 7, 569–578 (2011).
Hill, A. B. The environment and disease: association or causation? Proc. R. Soc. Med. 58, 295–300 (1965).
Hentschel, E. et al. Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer. N. Engl. J. Med. 328, 308–312 (1993).
Devoy, A., Bunton-Stasyshyn, R. K., Tybulewicz, V. L., Smith, A. J. & Fisher, E. M. Genomically humanized mice: technologies and promises. Nature Rev. Genet. 13, 14–20 (2012).
Shulzhenko, N. et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nature Med. 17, 1585–1593 (2011).
Reshef, D. N. et al. Detecting novel associations in large data sets. Science 334, 1518–1524 (2011).
Islami, F. & Kamangar, F. Helicobacter pylori and esophageal cancer risk: a meta-analysis. Cancer Prev. Res. 1, 329–338 (2008).
Blaser, M. J., Chen, Y. & Reibman, J. Does Helicobacter pylori protect against asthma and allergy? Gut 57, 561–567 (2008).
Tana, C. et al. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol. Motil. 22, 512–519 (2010).
Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57–63 (2011).
Larsson, E. et al. Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut 23 Nov 2011 (doi:10.1136/gutjnl-2011-301104).
Backhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004).
Turnbaugh, P. J. et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci. Transl. Med. 1, 6ra14 (2009).