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Genome, Metagenomic Sequence Data Highlight Microbe Adaptations to Human Guts

NEW YORK – A team led by investigators from the Wellcome Sanger Institute has characterized genomic adaptations in beneficial gut microbes that get passed from one host individual to the next, focusing on forms of Firmicutes phylum bacteria from the gut microbiome that do or do not produce spores.

"Even though transmission of gut bacteria between humans is essential for their survival, the genetic and biological features of the bacteria that allows them to do this is still poorly understood," first author Hilary Browne, a Wellcome Sanger Institute staff scientist, said in a statement. "This research starts to unravel some of this mystery by analyzing the genomes and finding that the ability of bacteria to produce spores has been lost multiple times, impacting their evolution and function."

For a study published in Genome Biology on Thursday, the researchers brought together whole-genome sequence data for 1,358 Firmicutes representatives isolated from environmental sites or from host individuals, comparing them to one another and to dozens of other genomes from non-spore forming bugs from several other dominant gut phyla such as Bacteroidetes.

In the process, they identified several distinct Firmicutes lineages that appear to have lost their spore-forming abilities, based on comparisons with sequences from other spore-forming bugs, machine learning analyses, and the presence or absence of some 66 sporulation-related genes. In general, they noted, "Former Spore Formers" with low sporulation-associated gene signatures tend to have streamlined genomes and metabolic specializations that may reflect adaptation to human hosts, including a shift from genes linked to metabolite production to those involved in metabolite transport.

"Our results suggest host adaptation in gut Firmicutes is an evolutionary trade-off between transmission range and colonization abundance," the authors reported, adding that "[w]e reveal host transmission as an underappreciated process that shapes the evolution, assembly, and functions of gut Firmicutes."

The team suggested that the sporulation-free forms of Firmicutes are particularly prominent in the gut microbiomes of some individual hosts, despite being relatively uncommon across broader human populations — findings shored up with phenotypic experiments and analyses on metagenomic sequences for fecal samples from 9,966 individuals spanning countries on half a dozen continents.

"Human population-level metagenomic analysis reveals bacteria no longer capable of sporulation are more abundant in individuals but less prevalent compared to spore-formers," the authors reported, "suggesting increased colonization capacity and reduced transmission range are linked to host adaptation within the human intestinal microbiota."

Browne noted that "[i]t is necessary to continue looking at the genetic detail of the microbiome to help understand the roles of specific bacteria, and how lacking these might impact human health." Even so, such findings provide a look at the ways that symbiotic bacteria can move between individuals, and the adaptations that occur along the way, offering a window into the wider transmission of microbes that make up human microbiomes.

"The microbiome plays an essential role in human health and development, and influences a wide range of physiological functions in the body," senior author Trevor Lawley, a host-microbiota interactions researcher at the Sanger Institute, said in a statement. "Understanding more about the bacteria that inhabit us and how they are adapted to living in humans through their metabolism will be important for the development of new therapeutics and diagnostics for microbiome-mediated diseases."