A new study led by researchers at the Helmholtz Institute for Functional Marine Biodiversity sheds light on a previously little-studied component of the human intestinal flora: plasmids. These small extrachromosomal genetic elements are ubiquitous in bacterial cells and can significantly influence microbial lifestyles, yet their diversity in natural habitats has remained poorly understood.
In a study published in Cell, the team reported the identification of a mysterious plasmid, called pBI143, that is one of the most numerous genetic elements in the human gut. This plasmid is present in the intestines of more than 90% of individuals in industrialized countries, making it a potentially powerful biomarker for identifying health hazards such as fecal contamination of water or human disorders like Inflammatory Bowel Disease.
Plasmids are common to cells from all domains of life. They can be exchanged between different bacterial cells and even between different types of bacteria, and they can provide their hosts with important fitness determinants, such as genes encoding antibiotic resistance.
However, the researchers also identified "cryptic plasmids," like pBI143, which do not appear to contain genes encoding obvious beneficial functions for their host. These plasmids have remained a mystery in microbial ecology, as from an evolutionary perspective, they should not exist at all.
To solve this problem, senior author A. Murat Eren and his colleagues developed a new machine learning approach that allowed them to identify over 68,000 plasmids in human intestinal flora, including the abundant pBI143 plasmid. Further analysis revealed that pBI143 is one of the most numerous genetic entities in the human gut, even more abundant than viral genomes, which were previously thought to be the most abundant extrachromosomal elements.
The researchers also found that pBI143 occurs almost exclusively in the human gut and is virtually absent in other environments, such as oceans, soils, and the digestive organs of animals. The only other samples in which the researchers detected the plasmid were in environments influenced by humans, such as wastewater, hospital surfaces, and laboratory rats.
Due to its prevalence and abundance, the researchers hypothesized that pBI143 could be used as a biomarker for detecting fecal contamination in drinking water, and they were able to demonstrate that it is a more sensitive marker than state-of-the-art biomarkers based on specific gene sequences of human intestinal bacteria.
Furthermore, the team identified another potential application of this prevalent genetic entity in the context of human disorders such as IBD. They found that the relative copy number of pBI143 increased almost four times in the intestines of people suffering from IBD compared to healthy individuals, suggesting that changes in the copy number of the plasmid could serve as a non-invasive method to quantify disease progress or severity.