Using roundworms, one of Earth's simplest animals, Rice University bioscientists have found the first direct link between a diet with too little vitamin B12 and an increased risk of infection by two potentially deadly pathogens.
Despite their simplicity, 1-millimeter-long nematodes called Caenorhabditis elegans (C. elegans) share an important limitation with humans: They cannot make B12 and must get all they need from their diet. In a study published today in PLOS Genetics, researchers from the lab of Rice biochemist and cancer researcher Natasha Kirienko describe how a B12-deficient diet harms C. elegans' health at a cellular level, reducing the worms' ability to metabolize branched-chain amino acids (BCAA). The research showed that the reduced ability to break down BCAAs led to a toxic buildup of partially metabolized BCAA byproducts that damaged mitochondrial health.
Researchers studied the health of two populations of worms, one with a diet sufficient in B12 and another that got too little B12 from its diet. Like the second population of worms, at least 10 percent of U.S. adults get too little B12 in their diet, a risk that increases with age.
B12 finding came as a surprise to researchers, which first noticed the effect in experiments designed to investigate the mechanisms of pathogenesis of Pseudomonas aeruginosa (P. aeruginosa), a potentially deadly disease in both worms and humans that infects some 51,000 U.S. hospital patients each year, according to the Centers for Disease Control.
Like thousands of others worldwide, Researcher used C. elegans as a model organism to study the effects of disease, drugs, toxins and other processes that affect humans and animals. In many C. elegans research labs worms are fed Escherichia coli (E. coli), a common human gut bacteria that is itself a model organism. They found that switching between E. coli strain OP50 and strain HT115 dramatically altered the worm's stress tolerance.
The key difference between the two diets is the ability of HT115 and OP50 to acquire B12 from the environment," said Revtovich, a research scientist. "We showed that HT115 is far more efficient at this, making about eight times as much of the protein that it needs to harvest B12 as compared to OP50. The researchers used numerous tests to confirm their results and rule out other possible mechanisms for the effect. They also found that C. elegans on an HT115 diet had the ability to resist infection by another deadly human pathogen, Enterococcus faecalis.