The Huck Institutes of the Life Sciences

Using metabolomics to discern nutrients’ influence on immunity

The Cantorna Lab’s collaboration with the Metabolomics Facility yields new insights.

“What we are interested in,” says Margherita Cantorna, “is how different nutrients regulate immune function. We have a project on vitamin D, a project on vitamin A, and then another focusing on edible mushrooms. Each of these projects involves the Metabolomics Facility and Andrew Patterson’s and Philip Smith’s expertise in metabolomics.”

All three projects, she explains, are also supported by a gnotobiotic animal facility, where germ-free mice (having no microbiota) are raised for experimental comparison with mice having a normal microbiota.

Vitamin A

“What we can do then,” Cantorna continues, “is to look at the different metabolites that are being made – with vitamin A and without vitamin A – in animals that have a microbiota and in animals that do not. By doing this we can figure out, of the metabolites we are measuring, which are being made by the microbiota.”

Any metabolites that are not being made by the microbiota, it follows, are therefore being metabolized by the host.

Vitamin D

The vitamin D we eat, Cantorna explains, is not the active nutrient in our bodies – it has to be metabolized twice in order to become active vitamin D.

“In addition,” she says, “active vitamin D is a really powerful drug, so the amount of it is regulated by our bodies’ breaking it down almost as soon as it is made.”

In order to investigate further, graduate student Stephanie Bora developed, with Phil Smith’s help, an assay to measure several of the key vitamin D metabolites in small volumes of blood.

“We have found that the microbiota regulates the ability of the host to metabolize vitamin D,” Cantorna says. “If you give vitamin D to an animal without a microbiota, it will have lower levels of several vitamin D metabolites than an animal with a microbiota, and so we know that the microbiota is helping to metabolize the vitamin D.”

Edible mushrooms

The Lab’s edible mushroom experiments “are pretty straightforward,” Cantorna notes. “Edible mushrooms in the diet have been shown to help repair gut injuries, which occur either because of chemicals or because of infection. We are trying to figure out if that is because of the host metabolizing and using these nutrients in the mushrooms, or if it is because of bacteria in the gut.”

Toward that end, postdoctoral scholar Yuan Tian is analyzing and comparing the metabolites in conventionally reared (having a normal microbiota) and germ-free (without a microbiota) mice fed the same diet, with the sole exception being the presence or absence of mushrooms.

“Tian is looking at the kind of metabolites you find in the liver, in the blood, in the cecum,” Cantorna explains, “to try to see what the effect of eating mushrooms is on the microbes and host metabolism. In the animals with a microbiota, what differences are there with just the variation in diet?”

Of the metabolites Tian finds, those which aren’t also present in the germ-free animals are, Cantorna says, “being produced by bacteria.”

Unifying theme

“Across the three projects,” Cantorna sums, “there are very similar themes – the connection between beneficial effects of nutrients either on immune function or gastrointestinal health, and how the microbiota is being influenced by these nutrients, as well as what the contribution is of the different kinds of microbes in our bodies to the metabolism of these nutrients and the effects we’re seeing. There are effects on the host and effects on the microbiota, and we’re trying to sort out which are which. Ultimately, can we do something as simple as giving people a food or a nutrient to change the microbiota and the whole metabolism in a way that benefits these various health and immune functions? That’s the bigger picture we are looking at.”