Gut-infecting superbug adapted to thrive with sugar-rich diet

Gut-infecting bacterium Clostridium difficile (C. diffcile) is evolving to thrive in people eating a Western sugar-rich diet, according to a new study published in Nature Genetics.

Researchers from the Wellcome Sanger Institute and London School of Hygiene & Tropical Medicine in England, along with other collaborators, identified genetic changes in the newly-emerging species that allow it to thrive on the sugar-rich diet, evade common hospital disinfectants, and spread easily. The researchers say the bacterium cause debilitating diarrhea, estimating this emerging species started to appear thousands of years ago, and accounts for over two thirds of healthcare C. difficile infections.

The study is the largest ever genomic study of C. difficile and shows how bacteria can evolve into a new species. It demonstrates that C. difficile is continuing to evolve in response to human behavior. The results could help inform patient diet and infection control in hospital, researchers said.

C. difficile bacteria can infect the gut and are the leading cause of antibiotic-associated diarrhea worldwide. While someone is healthy and not taking antibiotics, millions of good bacteria in the gut keep the C. difficile under control. However, antibiotics wipe out the normal gut bacteria, leaving the patient vulnerable to C. difficile infection in the gut. This is then difficult to treat and can cause bowel inflammation and severe diarrhea. Often found in hospital environments, C. difficile forms resistant spores that allow it to remain on surfaces and spread easily between people, making it a significant burden on the healthcare system.

To understand how this bacterium is evolving, researchers collected and cultured 906 strains of C. difficile isolated from humans, animals, such as dogs, pigs and horses, and the environment. By sequencing the DNA of each strain, and comparing and analyzing all the genomes, the researchers discovered that C. difficile is currently evolving into two separate species, according to Nitin Kumar, PhD, joint first author from the Wellcome Sanger Institute.

"The large-scale genetic analysis allowed us to discover that C. difficile is currently forming a new species with one group specialised to spread in hospital environments,” said Kumar in a statement. “This emerging species has existed for thousands of years, but this is the first time anyone has studied C. difficile genomes in this way to identify it. This particular bacterium was primed to take advantage of modern healthcare practices and human diets, before hospitals even existed."

The researchers found that this emerging species, named C. difficile clade A, made up approximately 70 percent of the samples from hospital patients. It had changes in genes that metabolize simple sugars, so the researchers then studied C. difficile in mice, and found that the newly emerging strains colonized mice better when their diet was enriched with sugar. It had also evolved differences in the genes involved in forming spores, giving much greater resistance to common hospital disinfectants. These changes allow it to spread more easily in healthcare environments, according to Trevor Lawley, PhD, senior author from the Wellcome Sanger Institute.

"Our study provides genome and laboratory-based evidence that human lifestyles can drive bacteria to form new species so they can spread more effectively,” said Lawley. “We show that strains of C. difficile bacteria have continued to evolve in response to modern diets and healthcare systems and reveal that focusing on diet and looking for new disinfectants could help in the fight against this bacteria."