Frederico Rey, PhD

Federico Rey, PhD

It has long been clear that “we are what we eat.” But a growing body of experimental data suggests it is not just what we eat, but how our individual gut microbiomes interact with diet that affects health.

“We are all colonized, but there is a large interpersonal difference in the communities that live in our guts,” said Federico Rey, PhD, assistant professor of bacteriology at the University of Wisconsin, Madison. “The challenge is to sort through the hundreds of different species to see what is going on.”

Dr. Rey simplifies the complexity by inoculating germ-free mice with limited communities that are representative of native human communities. He discussed the technique during an AGA Symposium on new tools and approaches to manipulate the human microbiome on Sunday.

One finding is that gut microbiome plays a role in the development of atherosclerosis. Humans with atherosclerosis and type 2 diabetes are deficient in Roseburia species, which produce butyrate. Butyrate has an anti-inflammatory role in immune cell migration and cytokine production.

Mice colonized with R. intestinalisfed diets high in plant polysaccharides showed increased production of butyrate compared to mice fed diets low in plant polysaccharides. And the mice with elevated butyrate production had significantly less atherosclerosis. There was no change in lipid levels.

R. intestinalisaffects energy metabolism, upregulating genes relating fatty acid metabolism and downregulating genes associated with response to glucose stimulus. Enterocytes switched energy substrates from glucose to butyrate, a short chain fatty acid.

At the same time, a diet high in plant polysaccharides favors increased colonization by R. intestinalis in mice. The same association between a high fiber diet and high levels of R. intestinalis has been seen in humans.

Peter Turnbaugh, PhD, assistant professor of microbiology and immunology at the University of California, San Francisco, has found similar interactions between a ketogenic diet high in fat and low in carbohydrates and the gut microbiome. A ketogenic diet favors the growth of Bacteroides species and a more robust mucosal barrier.

Less is known about how diet affects gut bacterial fitness. Bacteroides species use the intracellular signal guanosine pentaphosphatate, (pppGpp), to coordinate the expression of hundreds of genes between active growth and maintaining position in the highly competitive microbial community.

“Bacteria themselves do a much better job of controlling their own gene expression than we can do for them,” said Andrew Goodman, PhD, associate professor of microbial pathogenesis at Yale University School of Medicine, New Haven, CT. “They have a need not to grow in order to persist in the gut.”