A new study shows that mice with high levels of microbes that eat choline are often deprived of this essential nutrient. Compared to mice without choline-hungry bacteria, the choline-starved mice had an increased susceptibility to metabolic diseases and gave birth to pups with biochemical alterations in the brain that exhibited more anxious behaviors. The study was published late last week in Cell Host & Microbe by researchers from the University of Wisconsin–Madison and Harvard University.
Choline is among the resources that cells use to make modifications to DNA, and with less choline available, the cell's ability to modify and regulate genes can be impaired.
To test whether microbiomes were competing with their hosts for choline, a group lead by Federico Rey, professor of bacteriology at the University of Wisconsin–Madison, used germ-free mice that were colonized with defined populations of microbes. Some mice had choline eaters; others had communities where choline consumption was disrupted by mutation of a single gene.
When Kym Romano, a graduate student in Rey's group and one of the lead authors of the study, fed the mice a high-fat diet, which induces a range of metabolic diseases in mice, the animals with choline-eating microbes added more abdominal fat, and had fattier livers, than their counterparts with microbes that couldn't eat choline.
Romano also found that the offspring of mice with choline-eating bacteria had altered epigenetic patterns in their brains, suggesting problems with normal development. In mice that were genetically susceptible to behavioral problems, those that had choline-eating microbes showed more anxious behaviors. Mothers showed increased levels of infanticide and obsessive grooming, also indicative of increased anxiety.
Rey's team suspects that epigenetic regulation partly explains the negative effects of choline-eating microbiomes, the byproduct of bacterial choline metabolism, known as TMAO, is also linked to negative outcomes. In their experiments, Rey's lab observed much higher levels of TMAO in the mice that hosted choline-eating bacteria. The toxic TMAO might work together with disrupted epigenetic patterns to create the long list of metabolic and developmental disruptions seen in these animals.
This isssue isn't as easy as just adding more choline to one's diet as that could mean an increase in TMAO. For now, this study suggests that the complex link between nutrition, gut microbes, and host metabolism is vital for health. Many questions remain about how to improve outcomes, in mice and humans.
Image: Nacho Vivas, lab manager at the Rey Lab, checks on a group of germ-free mice inside a sterile environment. Image courtesy of Bryce Richter at the University of Wisconsin–Madison.