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Antibiotics Can Cause Pervasive, Persistent Changes To Microbiota In Human Gut

ScienceDaily (Nov. 19, 2008) — Using a novel technique developed by Mitchell Sogin of the Marine Biological Laboratory (MBL) to identify different types of bacteria, scientists have completed the most precise survey to date of how microbial communities in the human gut respond to antibiotic treatment.

Sogin, director of the MBL’s Josephine Bay Paul Center, and Susan Huse of the MBL, along with David Relman and Les Dethlefsen of Stanford University, identified pervasive changes in the gut microbial communities of three healthy humans after a five-day course of the antibiotic Ciprofloxacin. Their results are reported in the Nov. 18 issue of PloS Biology.

Using very conservative criteria, the scientists identified at least 3,300 to 5,700 different taxa (genetically distinct types) of bacteria in the human distal gut, and antibiotic treatment influenced the abundance of about a third of those taxa.

“You clearly get shifts in the structure of the microbial community with antibiotic treatment,” says Sogin. “Some bacteria that were in low abundance prior to treatment may become more abundant, and bacteria that were dominant may decrease in abundance. When you get these shifts, they may be persistent. Some individuals may recover quickly, and others won’t recover for many months.”

In all the individuals tested in this study, the bacterial community recovered and closely resembled its pre-treatment state within four weeks after the antibiotic course ended, but several bacterial taxa failed to recover within six months.

This raises questions about the health effects of perturbations to the human-microbial symbiosis in the gut, such as may occur with antibiotic treatment. Because specific microbial populations mediate many chemical transformations in the gut—and previous studies have related these processes to cancer and obesity, among other conditions—changes in the composition of the gut microbiota could have important, but as yet undiscovered, health effects.

“When you change the microbial population structure in the gut, you may affect how that population is keeping indigenous pathogens at manageable levels,” says Sogin. Bacteria that do not normally cause problems may begin to grow more rapidly, and cause disease.

The study is part of a large, international effort to fully characterize the microbiota in the human gut, which is the highest-density natural bacterial ecosystem known. Up to 100 trillion microbial cells reside in the gut, and this community plays essential roles in nutrition, development, metabolism, pathogen resistance, and regulation of immune responses.

Until recently, descriptions of human-associated microbiota were constrained by techniques of cultivating (and thus identifying) bacteria. Less than 20-40% of the microbes in the human distal gut, for example, have been cultured in the laboratory. Since the late 1980s, however, cultivation-independent microbial surveys have been developed that identify community members by genetic sequencing. Sogin’s technique, for example, which was used in this study, characterizes microbial populations by pyrosequencing short, hypervariable regions of one gene common to all microbes, the 16S rRNA gene. This technique reveals greater taxonomic richness in microbial samples at a fraction of the cost of traditional sequencing technologies.



Bacterial Balance Keeps Us Healthy: Microbial Genes in Gut Outnumber Genes in Human Body

ScienceDaily (Mar. 4, 2010) — The thousands of bacteria, fungi and other microbes that live in our gut are essential contributors to our good health. They break down toxins, manufacture some vitamins and essential amino acids, and form a barrier against invaders. A study published in Nature shows that, at 3.3 million, microbial genes in our gut outnumber previous estimates for the whole of the human body.

Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, working within the European project MetaHIT and in collaboration with colleagues at the Beijing Genomics Institute at Shenzhen, China, established a reference gene set for the human gut microbiome -- a catalogue of the microbe genes present in the human gut. Their work proves that high-throughput techniques can be used to sequence environmental samples, and brings us closer to an understanding of how to maintain the microbial balance that keeps us healthy.

"Knowing which combination of genes is necessary for the right balance of microbes to thrive within our gut may allow us to use stool samples, which are non-invasive, as a measure of health," says Peer Bork, whose group at EMBL took part in the analysis. "One day, we may even be able to treat certain health problems simply by eating a yoghurt with the right bacteria in it."

This catalogue of the microbial genes harboured by the human gut will also be useful as a reference for future studies aiming to investigate the connections between bacterial genetic make-up and particular diseases or aspects of people's lifestyles, such as diet.

To gain a comprehensive picture of the microbial genes present in the human gut, Bork and colleagues turned to the emerging field of metagenomics, in which researchers take samples from the environment they wish to study and sequence all the genetic material contained therein. They were the first to employ a high-throughput method called Illumina sequencing to metagenomics, dispelling previous doubts over the feasibility of using this method for such studies.

From a bacterium's point of view, the human gut is not the best place to set up home, with low pH and little oxygen or light. Thus, bacteria have had to evolve means of surviving in this challenging environment, which this study now begins to unveil. The scientists identified the genes that each individual bacterium needs to survive in the human gut, as well as those that have to be present for the community to thrive, but not necessarily in all individuals, since if one species produces a necessary compound, others may not have to. This could explain another of the scientists' findings, namely that the gut microbiomes of individual humans are more similar than previously thought: there appears to be a common set of genes which are present in different humans, probably because they ensure that crucial functions are carried out. In the future, the scientists would like to investigate whether the same or different species of bacteria contribute those genes in different humans.

The research was conducted within the European project MetaHIT, coordinated by Dusko Ehrlich at the Institut National de la Recherche Agronomique, in France, with genetic sequencing carried out by Jun Wang's team at the Beijing Genomics Institute at Shenzhen, China.