A new study has emerged which reveals just how little researchers still know about the human body and health. The microbiome refers to the microbes that reside in the human gut characterized as the other genome. Researchers from the Metagenomic of the Human Intestinal Tract ((MetaHIT) project, have managed to determine the highest quality integrated gene set for the human genome gut microbiome to date.
This microbial human gut reference catalog of over 9.8 million genes is freely accessible through the website and the data have also been deposited in BGI’s GigaScience Database, GigaDB and the SRA.
The gut is colonized by thousands of gut bacteria, which break down toxins, manufacture vitamins and essential amino acids and form a barrier against invaders. Researchers established a catalog of the human gut microbial genes by processing 249 new sequenced samples and 1,018 published samples as well as 511 sequenced genomes of gut related bacteria.
The researchers used the sequence data to investigate the composition of the colonized gut microbiota of healthy Chinese and Danish adults and determined that the composition greatly differed in the population suggesting an influence by difference in diet and environment. In addition, they observed enrichment in possible antibiotic resistance genes both at the population level (penicillin resistance in Danes and multidrug resistance in Chinese) and in the individual-specific genes, which highlighted the need for close monitoring of direct and indirect exposure to antibiotics.
The genes placed in the integrated gene catalog overwhelmingly represent individual specific genes consisting mainly of genes responsible for the synthesis of cell wall components, DNA-related functions such as transposases, endonucleases and DNA methylases and encoding phage-related proteins. Such individual-specific genes likely reflect adaptation and might reflect the distinct combination of genetic, nutritional and medical factors in a host.
Another new study presented at the American Society of Human Genetics has associated a humans immunity-related pathways to the composition of the microbiome. The microbiome refers to bacteria and other microbes that live in and on the body and form a biological network.
“These genes are significantly enriched in inflammatory and immune pathways and form an interaction network highly enriched with immunity-related functions,” said Ran Blekhman, Ph.D., Assistant Professor, Department of Genetics, Cell Biology, and Development at the University of Minnesota, Minneapolis.
The investigators highlighted the interaction between genetic variants and the different microbes that live on and in the human body on the skin, genital areas, mouth and other areas of the human body including the intestines colonized by trillions of bacteria and other micro-organisms.
Their study specifically detected that the human genetic variants correlated with the microbiome at two different levels: 1. the individual level where the genetic variation correlated with the overall structure of a person’s microbiome and 2. at the species level, where host human genetic variation linked to one particular bacterial species was identified.
To examine the specific bacterial species that inhabited each human body site, the researchers mined sequence data from the Human Microbiome Project (HMP), an international program to genetically catalog the microbial residents of the human body. They found that variation in genes related to immune system pathways was correlated with microbiome composition in 15 body sites.
“The results highlight the role of host immunity in determining bacteria levels across the body and support a possible role for the microbiome in driving the evolution of bacteria-associated host genes,” Dr. Blekhman said.
Another study which confirmed the link to an immune response based on the intestinal microbiome was published in the PLOS ONE journal. In this study researchers demonstrated that mice fed a gluten-free diet had a dramatic reduction in type 1 diabetes development.These mice were non-obese diabetic mice, or mice that grow to develop Type 1 diabetes and the gluten-free diet worked to protect the mice against Type 1 diabetes. When gluten was added back to the diet there was a measurable change in the composition of the bacterial flora.
“These changes suggest that the presence of gluten is directly responsible for the diabetes-creating effects of diet and determines the gut microflora,” said Govindarajan Rajagopalan, Ph.D., a Mayo Clinic immunologist and study author.
Eric V. Marietta, Andres M. Gomez, Carl Yeoman, Ashenafi Y. Tilahun, Chad R. Clark, David H. Luckey, Joseph A. Murray, Bryan A. White, Yogish C. Kudva, Govindarajan Rajagopalan. Low Incidence of Spontaneous Type 1 Diabetes in Non-Obese Diabetic Mice Raised on Gluten-Free Diets Is Associated with Changes in the Intestinal Microbiome. PLoS ONE, 2013; 8 (11): e78687 DOI: 10.1371/journal.pone.0078687
American Society of Human Genetics. “Gene variants in immune system pathways correlated with composition of microbes of human body.”
Junhua Li, Huijue Jia, Xianghang Cai, Huanzi Zhong, Qiang Feng, Shinichi Sunagawa, Manimozhiyan Arumugam, Jens Roat Kultima, Edi Prifti, Trine Nielsen, Agnieszka Sierakowska Juncker, Chaysavanh Manichanh, Bing Chen, Wenwei Zhang, Florence Levenez, Juan Wang, Xun Xu, Liang Xiao, Suisha Liang, Dongya Zhang, Zhaoxi Zhang, Weineng Chen, Hailong Zhao, Jumana Yousuf Al-Aama, Sherif Edris, Huanming Yang, Jian Wang, Torben Hansen, Henrik Bjørn Nielsen, Søren Brunak, Karsten Kristiansen, Francisco Guarner, Oluf Pedersen, Joel Doré, S Dusko Ehrlich, Nicolas Pons, Emmanuelle Le Chatelier, Jean-Michel Batto, Sean Kennedy, Florence Haimet, Yohanan Winogradski, Eric Pelletier, Denis LePaslier, François Artiguenave, Thomas Bruls, Jean Weissenbach, Keith Turner, Julian Parkhill, Maria Antolin, Francesc Casellas, Natalia Borruel, Encarna Varela, Antonio Torrejon, Gérard Denariaz, Muriel Derrien, Johan E T van Hylckama Vlieg, Patrick Viega, Raish Oozeer, Jan Knoll, Maria Rescigno, Christian Brechot, Christine M’Rini, Alexandre Mérieux, Takuji Yamada, Sebastian Tims, Erwin G Zoetendal, Michiel Kleerebezem, Willem M de Vos, Antonella Cultrone, Marion Leclerc, Catherine Juste, Eric Guedon, Christine Delorme, Séverine Layec, Ghalia Khaci, Maarten van de Guchte, Gaetana Vandemeulebrouck, Alexandre Jamet, Rozenn Dervyn, Nicolas Sanchez, Hervé Blottière, Emmanuelle Maguin, Pierre Renault, Julien Tap, Daniel R Mende, Peer Bork, Jun Wang. An integrated catalog of reference genes in the human gut microbiome. Nature Biotechnology, 2014; DOI: 10.1038/nbt.2942