More than 100 years ago Élie Metchnikoff said that “the dependence of the intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes”.
Ever since Metchnikoff for over 100 years in the modern era of biological science we have an increasing interest of the important role of our symbiotic microbiota. Next generation DNA sequencing certainly accelerated the study of metagenomics, the genetic background of a complex living system. We are all ascertained as a commensal life-entity, we just simple cannot ignore those microbial cells that overgrow our human cells by 10 times and it would be very un-scientific to ignore those millions of microbial genes interacting to influence human health and disease. Our commensal life with microbiota is a true symbiosis, we help and nurture each other, but I would say we, humans might have an upper hand, after all we look like humans and not bacteria. To support this, in 2015 (Ref-1) the first and so far only GWAS, where they study the association between genotype and potential phenotype at a genome wide screening level, they found that a single SNP, a human genetic variant is associated with the number of Akkermansia muciniphila bacterial cells harbored in the gut. Akkermansia muciniphila is smart, listens to the host genetic constellation.
Akkermansia muciniphila made itself interesting in 2004 to the scientific community when it was isolated for the first time (Ref-2) and the discovery group in the Netherlands and Belgium has been working on this bacterial strain very intensively, ever since. They have found out that Akkermansia muciniphila plays a crucial role in the symbiosis between the gut microbiota and the host that controls gut barrier and other physiological and homeostatic functions during obesity and type-2 diabetes. In the coming years they demonstrated (Ref-3) in purely laboratory setting using well controlled mouse experiments a dramatic decrease in Akkermansia muciniphila in both genetically and diet-induced obese and diabetic mice. Also, by restoring the physiological abundance of this strain in these experimental mice they were able to reverse the obese and diabetic pathological phenotype. Finally, they identified and isolated a protein (Ref-4) in the bacterial wall and they called it amuc-1100 that is associated with the host metabolic health. Amazingly, amuc_1100 is a drug candidate in human clinical trial by now, well tolerated and now paves the way for future human therapeutic tools of microbial origin.
Growing research interest in this field of metagenomics has resulted in the discovery of amuc_1100 and its role in human obesity and type-2 diabetes. This is the first bacterial protein linked directly with human disease. This is the first one and there are million more to discover and as a result of our research we are going to be able to curate microbial genes that are associated with human phenotype. This first direct scientific link between the bacterial gene and human phenotype proves that indeed we, scientists need to go into this direction in our research efforts. If we do any research, most importantly with the aim to cure cancer we must study bacterial genetic association with cancerogenesis, otherwise we are not serious in our effort.
“Knowledge is always good and certainly always better than ignorance”–Sergey Brin
“Possideo genes ergo sum”—Anonymous Roman Philosopher
Reference
- Genome-Wide Association Studies of the Human Gut Microbiota; Emily R. Davenport, Darren A. Cusanovich, Katelyn Michelini, Luis B. Barreiro, Carole Ober, Yoav Gilad; PLOS ONE | DOI:10.1371/journal.pone.0140301 November 3, 2015
- Akkermansia muciniphila gen. nov., sp. nov.,a human intestinal mucin-degrading bacterium; Muriel Derrien, Elaine E. Vaughan, Caroline M. Plugge and Willem M. de Vos; International Journal of Systematic and Evolutionary Microbiology (2004), 54, 1469–1476
- Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity; Amandine Everard, Clara Belzer, Lucie Geurts, Janneke P. Ouwerkerk, Céline Druart, Laure B. Bindels, Yves Guiot, Muriel Derrien, Giulio G. Muccioli, Nathalie M. Delzenne, Willem M. de Vos and Patrice D. Cani; PNAS (2013), 110(22), 9066–9071
- A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice; Hubert Plovier, Amandine Everard, Céline Druart, Clara Depommier, Matthias Van Hul, Lucie Geurts, Julien Chilloux, Noora Ottman, Thibaut Duparc, Laeticia Lichtenstein, Antonis Myridakis, Nathalie M Delzenne, Judith Klievink, Arnab Bhattacharjee, Kees C H van der Ark, Steven Aalvink, Laurent O Martinez, Marc-Emmanuel Dumas, Dominique Maiter, Audrey Loumaye, Michel P Hermans, Jean-Paul Thissen, Clara Belzer, Willem M de Vos and Patrice D Cani; Nature Medicine advance online publication, published online 28 November 2016; doi:10.1038/nm.4236
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