Every human being has a genetic heritage, which is passed to us from our parents, and a unique microbiota, a set of bacteria, viruses and fungi that inhabit our body and outnumber our own cells. Unlike our genome, the composition of the microbiota depends on a series of non-hereditary factors (age, diet, use of antibiotics, just to name a few). While scientific research on human genome has been going on for a long time, studies on the microbiota are more recent. Through the analysis of a person’s microbiota it is possible to identify the microorganisms that characterize his or her personal set and, potentially, to establish his or her risk to develop certain diseases. “Almost all the microbial strains in healthy people have functional properties that are indispensable for the human body; for example, they help in digestion. However, the presence of certain variants of non-pathogenic microorganisms, explains Nicola Segata, head of the Laboratory of Computational Metagenomics at the Centre for Integrative Biology (CIBIO) of the University of Trento, may involve a higher risk to contract complex and/or autoimmune diseases like diabetes, Crohn disease and ulcerative colitis.
A “computational microscope”
Nicola Segata has been working on the Human Microbiome Project since its beginnings. The project was launched more than five years ago by the US National Institutes of Health (NIH) with the aim of mapping all microorganisms in the world population. “This revolution, explains Segata, is called metagenomics: it is a methodology based on biotechnologies to detect a person’s microorganisms from stools or saliva samples through the sequencing of genetic material and the computational analysis of data. The classic approach would require the cultivation of microorganisms in laboratory: this practice has other advantages but is slow, expensive and very difficult for most of pathogenic and non-pathogenic bacteria”. Segata from CIBIO has already developed, in the framework of the Human Microbiome Project, a first version of the approach that enables the simultaneous study of hundreds of different strains that can be found in the microbial set of an individual. “It’s like having a computational microscope that we can use to identify the inhabitants of our microbiota and differentiate with precision similar bacteria that have very different functions. By analyzing these differences, we might be able to find a link between specific usually harmless bacteria and some chronic and degenerative diseases”. What is the potential of Segata’s “microscope”?
Population mapping
“Thanks to the new tool that we have developed, which is an open source software, we have created a high resolution map of the gut strains of over two thousand complex bacteria communities of individuals belonging to different populations. We have observed that populations from different continents have specific variants of the same bacterium: it is as if some bacteria had learned to adapt to the diet and lifestyle of the people harboring them. The ambitious aim of the project, in perspective, is to establish relations between some diseases and the presence of specific strains of gut bacteria, and to open a large scale epidemiological study of many microorganisms that are currently little known”. “Nature Methods” published today an article on the subject, with the title “Strain-level microbial epidemiology and population genomics from shotgun metagenomics”. The article is signed by seven researchers at the CIBIO (Matthias Scholz, Edoardo Pasolli, Thomas Tolio, Moreno Zolfo, Francesco Asnicar, Duy Tin Truong, Adrian Tett) and by Nicola Segata, principal investigator. Among the authors are also Doyle V. Ward (Center for Microbiome Research, University of Massachusetts) and Ardythe L. Morrow (Department Pediatrics, Perinatal Institute, Cincinnati).
Necrotizing enterocolitis: a study on preterm infants
“In another study, continues Segata, we have used the new tool to focus on a group of infants, born ahead of time in the United States between the 23rd and the 29th week of pregnancy, at high risk of developing an extremely serious disease known as necrotizing enterocolitis. In the intestines of these infants we have found some strains of the E. coli bacterium, which are connected to the disease. The research might now aim at preventing these particular strains from colonizing the infants’ intestines or at developing targeted therapeutic approaches”. Last Thursday, “Cell Reports” published an article on the subject: “Metagenomic sequencing with strain-level resolution implicates uropathogenic E. coli in necrotizing enterocolitis and mortality in preterm infants”. The leading author of the study is Doyle Ward (Center for Microbiome Research, University of Massachusetts), with Matthias Scholz as co-author and Segata and Ardythe L. Morrow (Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati) as senior co-authors. Apart from Scholz and Segata, Moreno Zolfo and Adrian Tett from CIBIO also contributed to the study, with Diana H. Taft and Kurt R. Schibler from the Cincinnati center.
Research and Trentino - The CIBIO Laboratory of Computational Metagenomics, which employs about a dozen young academics and researchers, is involved in a number of international research projects and also collaborates with local organizations. “We are studying the transmission of the microbiota from mother to child, says Segata, with the division of Obstetrics and Neonatology of the main hospital in Trento, Italy. Thanks to funding from the Fondazione Caritro, in the past two years we have recruited some forty mother/child couples to learn about the bacterial colonization of infants’ intestines from the very first moments of life. With Terme di Comano and the Dermatology division of the S. Chiara hospital we are studying dermatological patients: we compare their bacterial strains to understand their relationship with a number of skin disorders like psoriasis and atopic dermatitis, and establish whether the effectiveness of the spa treatment is in part due to a change in the skin microbiota. We are also involved in the study of pathogenic bacterial strains in people with cystic fibrosis in collaboration with the Centro Trentino di Fibrosi Cistica (cystic fibrosis center at the Santa Maria del Carmine hospital)”.