My mailbox got choked up the other morning with emails from friends and strangers wondering about my thoughts on the recent study published in Nature on the mapping of gut bacterial (microbiome) patterns to basically three general groups. The findings were extensively reported in the media, including Wired Magazine which managed to start the article off with the bizarre claim that humans can belong to any one of eight blood groups. Although I suspect that the writer was alluding to ABO and Rhesus (4*2=8) that is not a very accurate way of putting things, since there are a large number of determinants, and in fact the secretor status (FUT2) that controls ABO presence in bodily secretions is much more significant ‘blood group’ on a phenotypic level that Rhesus (Rh), which is a true erythrocyte antigen and not found in the gut or body secretions.

The authors found three distinctive “enterotypes,” or bacterial communities dominated by a distinct genus — Bacteroides, Prevotella or Ruminococcus — each of which is found with a particular community of bacteria.

The abstract describes the study as follows:

By combining 22 newly sequenced fecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake.

There is much being made out of the apparent similarities between these enterotypes and the human blood groups. And well there should be. Except the link between blood groups and the microbiome is already well-known. I first wrote about it in my book Live Right For Your Type over ten years ago. (1)

Background

The distal human intestine represents an anaerobic bioreactor programmed with an enormous population of bacteria, dominated by relatively few divisions that are highly diverse at the strain/subspecies level. This microbiota and its collective genomes (microbiome) provide us with genetic and metabolic attributes we have not been required to evolve on our own, including the ability to harvest otherwise inaccessible nutrients. New studies are revealing how the gut microbiota has coevolved with us and how it manipulates and complements our biology in ways that are mutually beneficial.

We are also starting to understand how certain keystone members of the microbiota operate to maintain the stability and functional adaptability of this microbial organ. It is estimated that the human digestive tract may contain up to 100 trillion microorganisms (2) and the human gut may host up to 500-1000 different species of bacteria, of which as little as 7% have been successfully cultured in the laboratory. (3)

The human GI tract is predominantly a bacterial ecosystem. Cell densities in the colon (1011-1012/ml contents) are the highest recorded for any known ecosystem. The vast majority of phylotypes belong to two divisions (superkingdoms) of Bacteria: the Bacteroidetes (48%) and the Firmicutes (51%). The remaining phylotypes are distributed among the Proteobacteria, Verrucomicrobia, Fusobacteria, Cyanobacteria, Spirochaetes, and the candidate phylum VadinBE97.

Gut bacteria can have direct effects on gene activation that may be essential for proper gut development. Bacteria induced expression of mammalian genes has been known since the 1980’s when Japanese researchers were able to show that a fucosyltransferase enzyme (fucosyl-asialo GM1) was induced by bacteria but was absent from germ-free strains. (4)

This is especially interesting in light of the fact that many of the fucosyltransferase enzymes convey blood group and/or secretor status. (5) Human feces contain enzymes produced by enteric bacteria that degrade the A, B, and H blood group antigens of gut mucin glycoproteins.

The autosomal dominant ABH secretor gene together with the ABO blood group gene controls the presence and specificity of A, B, and H blood group antigens in human gut mucin glycoproteins. There is evidence that the host’s ABO blood group and secretor status affects the specificity of blood group-degrading enzymes produced by his fecal bacteria in vitro. (6)

In essence, bacteria ‘eat right for their type’ even if we sometimes don’t.

Comparatively small populations of fecal bacteria produce blood group-degrading enzymes but their presence is highly correlated with the ABO /secretor phenotype of the host: Fecal populations of B-degrading bacteria were stable over time, and their population density averaged 50,000-fold greater in blood group B secretors than in other subjects. In fact, the large populations of fecal anaerobes may be an additional source of blood group antigen substrate for blood group antigen degrading bacteria: antigens crossreacting with blood group antigens were detected on cell walls of anaerobic bacteria from three of 10 cultures inoculated. (7,8)

Another example of “eco-phenotypic cooperation” between a host’s polymorphism and gut bacteria may be seen in the development of the early vascular networks. In this case a mechanism of postnatal animal development, where microbes colonizing a mucosal surface are assigned responsibility for regulating elaboration of the underlying microvasculature by signaling through a bacteria-sensing epithelial cell and its possible relation to a polymorphic phenotype on the part of the host.

1. D’Adamo P, Whitney C. Live Right For Your Type. 2001. GP Putnam and Sons, NYC
2. Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. Mar 25; 307(5717):1915-20. (2005)
3. http://www.genome.gov/25521743
4. Eckburg, P. B., Bik, E. M., Bernstein, C. N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S. R., Nelson, K. E. & Relman, D. A. Diversity of the human intestinal microbial flora. Science 308, 1635-38. (2005)
5. Umesaki Y. Immunohistochemical and biochemical demonstration of the change in glycolipid composition of the intestinal epithelial cell surface in mice in relation to epithelial cell differentiation and bacterial association. J Histochem Cytochem. 1984 Mar; 32(3):299-304.
6. D’Adamo PJ, Kelly GS. Metabolic and immunologic consequences of ABH secretor and Lewis subtype status. Altern Med Rev. Aug;6(4):390-405; 2001
7. Hoskins LC, Boulding ET. Degradation of blood group antigens in human colon ecosystems. I. In vitro production of ABH blood group-degrading enzymes by enteric bacteria. J Clin Invest Jan;57(1):63-73;1976
8. Hoskins LC, Boulding ET. Degradation of blood group antigens in human colon ecosystems. II. A gene interaction in man that affects the fecal population density of certain enteric bacteria. J Clin Invest Jan;57(1):74-82; 1976

Tags: enterocytes