Gut Microbiota: Our Native Flora
Charting alterations in H. pylori and other human-dwelling microbes has been aided by the ability to sequence large amounts of microbial 16S rRNA, a sort of bacterial bar code that identifies each species. Recent work has provided a much fuller picture of which species are present in the gut and in what proportions and has revealed connections between changes in other gut-dwelling microbes and rising rates of obesity and metabolic syndrome.
Two major initiatives should now further expand our understanding of what bacterial species exist in our bodies, what they’re doing there and how they may differ from one person to the next. By cataloguing the microbial genome, or microbiome, the Human Microbiome Project, launched by the National Institutes of Health in 2007, attempts to answer those questions. A similar undertaking financed by the European Commission, called MetaHIT, has the same goal but focuses specifically on the human intestinal tract.
The first results from the MetaHIT project, published in March in Nature, consist of a census of the microbial genes, collected via fecal samples, that are present in the human digestive system. The number topped out at 3.3 million genes, representing approximately 1,150 species, with 57 species shared among more than 90% of individuals. This suggests there may be a core set of microbes that most people carry. But there was also a wide variety in the relative abundance of the most common species from person to person. The sheer number of genes suggests a greater microbial diversity than scientists had predicted, and it dwarfs the human genome, which consists of roughly 20,000 genes.
The Human Microbiome Project encompasses studies in which researchers aim to develop a reference collection of microbial genomes. In the May 21, 2010 issue of Science, the HMP published an analysis of 178 of them—the beginning of a collection that may eventually include 900 species. In the project’s second phase, studies will attempt to associate specific microorganisms with states of health and illness. Another main goal is to develop tools to advance the field of metagenomics, the analysis of genetic material from a mixed community of organisms. This will let researchers look in more detail at how microbes interact with human physiology.
Other research is already pulling back the curtain. A team led by Andrew Gewirtz, an immunologist at Emory University School of Medicine in Atlanta, studied a group of mice genetically engineered to be without a protein called Toll-like receptor 5, which is normally found in the intestines. TLR5’s function is to recognize the protein flagellin, which makes up the tails that bacteria use to move. Detecting flagellin from an invading pathogen, the protein mobilizes production of cytokines. A tenth of the mice lacking TLR5 developed severe colitis, while 30% showed less severe colitis, and the remainder exhibited overall inflammation and higher weight. To rule out the possibility that the inflammation was caused by an infection, Gewirtz then “re-derived” the mice, a process by which embryos from the genetically altered mice are transplanted into germ-free mothers.
Gewirtz and his colleagues found that the re-derived TLR5-deficient mice began to overeat; became obese; and developed high blood pressure, high cholesterol and insulin resistance—all key features of metabolic syndrome. Those changes occurred alongside alterations in the gut microbiota of the mice. When their intestinal bacteria were transplanted into typical mice with the TLR5 gene but no existing microbiota, the new mice developed many of the same symptoms—suggesting that the change in the composition of the gut microbiota, rather than the lack of the TLR5 protein, leads to metabolic syndrome.