Microbial solutions for metabolic disorders
MARCH 2026
You may have heard advertisements for ZBiotics, bacteria engineered to prevent hangovers by supplying extra acetaldehyde dehydrogenase. The elegant idea of using microorganisms to treat a hangover – basically, a temporary metabolic disorder – has gone mainstream. But getting microorganisms to treat permanent (genetic) metabolic disorders may be more difficult, as the results of recent clinical trials indicate.
In a recent paper, Judy Fridovich-Keil's lab showed that a strain of yeast can deliver the ability to metabolize dietary galactose to a rat model of galactosemia. The yeast strain was created through “adaptive evolution” by a San Diego-based startup company called GutsyBio, which is developing fungal treatments for galactosemia and hereditary fructose intolerance.
In this pilot study, the yeast was given to the rats just before the galactose, and the authors didn’t expect the yeast to survive long-term in the mammalian gut. The idea behind the yeast treatment is to give people living with galactosemia a temporary metabolic safety net. An example: if they wanted to be able to eat a normally forbidden treat at a party. Still, how any yeast treatment should be implemented in the clinic or at home needs to be worked out.
Taking an analogous approach, a company called Synlogic Therapeutics was testing a bacterial strain engineered to metabolize phenylalanine in people with phenylketonuria. However, Synlogic folded in 2024 after reporting poor results in their phase III PKU clinical trial. A post-mortem interview with one of the investigators, Neal Sondheimer from Toronto’s SickKids, suggests that durability of the bacteria in the gut and ensuring consistent dosing and delivery were challenges. Yeast probiotics, which have been tested in some clinical trials for IBS, might be hardier in there?