Microbes could deprive a person of nutrients

High levels of microbes that eat choline can lead to a lack of nutrients, according to a new study published in Cell Host & Microbe.

Comparing mice with high levels of microbes to those who do not have “choline-hungry bacteria”, Federico Rey, a Professor of Bacteriology at the University of Wisconsin, found that those with low levels of choline had health and development issues. These included being more susceptible to metabolic diseases and giving birth to mice who appeared to be more anxious due to biochemical changes in the brain.

“Gut bacteria get to use a lot of our food before we do,” explained Rey.

Gut bacteria that consumes high levels of choline can be caused by epigenetic regulation, which is the decorating of genes with chemical groups that control how much they are expressed. With limited choline available, it hinders the ability of cells to modify and regulate genes. This was evident in choline-deficient mice, who exhibited altered epigenetic patterns in tissues such as the liver and the brain.

“Epigenetic modifications change how genes are expressed,” said Kym Romano, one of the lead authors of this research. “These modifications are also what make our liver a liver and our heart a heart.”

To test whether microbiomes could compete with their hosts for this essential nutrient, Rey’s group used germ-free mice that were colonised with defined populations of microbes. Some mice had choline eaters while others had communities where choline consumption was disrupted by mutating a single gene.

On a high-fat diet, which induces a range of metabolic diseases in mice, the animals with choline-eating microbes had increased levels of abdominal fat and fattier livers than their counterparts with microbes that couldn’t eat choline.

Pregnancy increases the demand for choline, which can be found in foods such as eggs, fish, cauliflower and milk. The nutrition is needed to support epigenetic regulation and cellular health in the developing foetus, and previous studies have suggested that choline deficiency during pregnancy is linked to children with altered behaviour.

This was reinforced in the study, which looked at the effects of choline-eating microbes across generations. Romano found that the offspring of mice with choline-eating bacteria had problems with normal development and showed more anxious behaviours, like burying marbles in their cages.

“There are already human studies that show that choline deficiency is a problem that matters to human health, and what this study really provides is one possible mechanism by which this may be exacerbated,” said Rey.

While this work suggests that the complex link between nutrition, gut microbes and host metabolism is vital for health, many questions remain about how to improve outcomes, either in mice or in humans.

A higher intake of choline in the diet might lead to more of the by-product of bacterial choline metabolism, known as TMAO. The study found that mice that hosted choline-eating bacteria had higher levels of TMAO. The toxic TMAO could work with disrupted epigenetic patterns to cause metabolic and developmental problems.

“As any good science project goes, we scratched the surface of an answer but opened up a million more doors to go through,” said Romano.