Medical Hypotheses 74 (2010) 214–215

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Medical Hypotheses

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Editorial

The human superorganism – Of microbes and men

a r t i c l e i n f o

Article history:Received 11 August 2009Accepted 14 August 2009

0306-9877/$ - see front matter � 2009 Elsevier Ltd. Adoi:10.1016/j.mehy.2009.08.047

s u m m a r y

Albert Einstein once said that ‘‘The true value of a human being can be found in the degree to which he hasattained liberation from the self”. For years our traditional view of ‘self’ was restricted to our own bodies;composed of eukaryote cells encoded by our genome. However, in the era of omics technologies and sys-tems biology, this view now extends beyond the traditional limitations of our own core being to includeour resident microbial communities. These prokaryote cells outnumber our own cells by a factor of tenand contain at least ten times more DNA than our own genome. In exchange for food and shelter, thissymbiont provides us, the host, with metabolic functions far beyond the scope of our own physiologicalcapabilities. In this respect the human body can be considered a superorganism; a communal group ofhuman and microbial cells all working for the benefit of the collective – a view which most certainlyattains liberation from self.

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It is now almost a decade and a half since the first sequence of afree living organism (a bacterium called Haemophilus influenzae)was published in the journal Science in 1995 [1]. This reducedthe time taken to complete a genome sequencing project from13 years to four months. However, rapid advances in modern se-quence capabilities and technologies [2] means that today, the en-tire H. influenzae genome can now be sequenced in as little as twohours. Several hundred genomes have been sequenced to date,including most human pathogens, several plants, insects and mam-mals; including our own human genome, published in 2001 [3,4] –the genomics era has well and truly arrived. Indeed, more than 350biomedical advances – diagnostic tests, drugs, treatments and vac-cines – have begun clinical trials since the sequence was com-pleted; allowing scientists to ‘read’ the ‘book of Life’ that is thehuman genome.

While it is only human nature to regard our own genome as thepinnacle of the genomics era, the human genome initiative has, interms of sequencing potential, merely scratched the surface [5].Humans after all represent only a small fraction of all the animalson earth, which in total constitutes less than 0.1% of the plant’s to-tal biomass. Microbes on the other hand (numbering �4–6 � 1030)account for more than 50% of the earth’s biomass, and as such rep-resent a huge and as yet untapped source of genetic information.Furthermore, 99% of these microbes fail to grow under standardlaboratory conditions and as such have, until now, remained lar-gely invisible to the microbe–hunters [6]. Thus, if the human gen-ome can be thought of as the book of life, then using this analogy,the metagenome (the totality of genetic information from all livingorganisms including viruses, in a particular environment) can bethought of as the ‘library of life’.

Bacteria occupy all surfaces of the human body with a com-bined microbial cell population �10 times that of human cells[7], a fact which, in essence, makes us more microbe than man!The human colon (large intestine) for example, has been identi-fied as the most densely populated natural bacterial ecosystem,

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encompassing more bacterial cells than all of our microbial com-munities combined [8]. The total number of genes encoded bytheir collective genomes (referred to as the gut microbiome) isat least one order of magnitude greater than the human genome[9].

It should come as no surprise then that the human gastrointes-tinal microbiota functions as a ‘virtual organ’; bestowing metabolicfunctions that are far beyond the scope of our own human physiol-ogy; such as improved strategies of energy harvest from ingestedfoods, synthesis of essential vitamins and the degradation of com-plex plant polysaccharides. Indeed, imbalances in this intestinalmicrobial community structure have the potential to cause manydebilitating conditions such as Crohn’s disease, inflammatory bo-wel disease (IBD), allergy, obesity, and even cancer [7]. Thus, it isbecoming increasingly evident that this human/microbe symbiosisis a defining feature of human physiology, creating a new view ofourselves as superorganisms – collections of cells acting in concertto produce phenomena governed by the collective [10].

Perhaps the most significant recent advance in metagenomic re-search to date is the establishment of the Human Microbiome Ini-tiative (HGMI); an interdisciplinary world wide effort to gain agreater appreciation for the microbial components of the humangenetic and metabolic landscape and how they contribute to nor-mal physiology and predisposition to disease [11]. The aim of thisinitiative, which has been described as a logical conceptual exten-sion of the human genome project, is to produce deep draft wholemetagenome sequences for reference genomes (100 species indic-ative of the bacterial divisions or superkingdoms within the gut)followed by a shallower 16S rRNA gene and community datasetfrom a moderate number of samples. Many outcomes are predictedfor the Human Microbiome Project (HMP), including the identifica-tion of new biomarkers for health and medicine, new enzymescapable of degrading xenobiotics in biotechnology and ultimatelya more complete understanding of the nutritional requirementsof humans.

Editorial / Medical Hypotheses 74 (2010) 214–215 215

In conclusion then, our established view of ‘self’ must extendbeyond the traditional limitations of our own ‘flesh and blood’ toinclude our resident microbial communities. Ultimately, an inte-grated analysis of the rapidly evolving ‘omics’ technologies: meta-transcriptomes, metaproteomes and metametabolomes, will beneeded to sustain the logical next phase of this molecular intro-spection – human systems biology – the interdisciplinary analysisof complex biological networks across multiple hierarchical levelsin situ, from microbes to man. Such systems based understandingof microbial communities in a global human context may eventu-ally help to answer some of the most important questions of ourtime; such as how best to optimise human nutrition and health,and even how to control the emerging pandemic of antibioticresistance.

Acknowledgements

Dr. Roy Sleator is a Health Research Board (HRB) and Alimen-tary Pharmabiotic Centre (APC) Principal Investigator. The authorwishes to acknowledge the continued financial assistance of theHRB and APC.

References

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[2] Tettelin H, Feldblyum T. Bacterial genome sequencing. Methods Mol Biol2009;551:231–47.

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[4] Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. Thesequence of the human genome. Science 2001;291:1304–51.

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[6] Amann RI, Binder BJ, Olson RJ, Chisholm SW, Devereux R, Stahl DA.Combination of 16S rRNA-targeted oligonucleotide probes with flowcytometry for analyzing mixed microbial populations. Appl EnvironMicrobiol 1990;56:1919–25.

[7] Kurokawa K, Itoh T, Kuwahara T, Oshima K, Toh H, Toyoda A, et al. Comparativemetagenomics revealed commonly enriched gene sets in human gutmicrobiomes. DNA Res 2007;14:169–81.

[8] Frank DN, Pace NR. Gastrointestinal microbiology enters the metagenomicsera. Curr Opin Gastroenterol 2008;24:4–10.

[9] Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterialmutualism in the human intestine. Science 2005;307:1915–20.

[10] Kinross JM, von Roon AC, Holmes E, Darzi A, Nicholson JK. The human gutmicrobiome: implications for future health care. Curr Gastroenterol Rep2008;10:396–403.

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Roy D. SleatorDepartment of Biological Sciences,

Cork Institute of Technology,Bishopstown,

Rossa Avenue,Cork, Ireland

Alimentary Pharmabiotic Centre,University College Cork,

Cork,Ireland

Tel.: +353 (0)21 4326885; fax: +00 353 21 4328851E-mail address: roy.sleator@cit.ie