A Gut Feeling about Genetics, Health, and Adaptation to various diets

For the last year or so I've had this persistent thought about how flora, our intestinal flora, is very important in our ability to adapt to different diets and how healthy we are. It might explain why some people have celiac, why some people have IBS, why some people are obese, and so forth. And, perhaps why some people are not as healthy on this or that diet.

This was just an intuition. However, today I found this study in Scientific American and I've excerpted the interesting points below:

Genetics in the Gut: Intestinal Microbes Could Drive Obesity and Other Health Issues:
The diversity of germs in the human gut suggests microbiota play a greater role in health than previously thought, even driving obesity and other metabolic conditions

More here: Uncovering the genetic secrets of intestinal bacteria


Excerpts:

Stomach survey
The number of microbes in the human gut was known to be vast, but the 3.3 million microbial genes located in it were a good deal "more than what we originally expected," says Jun Wang, of BGI and co-author of the Nature study. The number was especially surprising given that the microbiota tended to be very similar across the 124 individuals they sampled in Denmark and Spain.

Previous work had scanned for these microbial genes in the past. The largest had created about three gigabases (billion base pairs) of microbial sequences that was trumped by Wang's team, which assembled more than 576 gigabases.

The hefty catalogue is a "big advance" in the field, says Andrew Gewirtz of the Department of Pathology and Laboratory Medicine at Emory University who was not involved in this study. "It really sets in place a framework for defining—in detail—the microbiome," he says. And as Wang and his colleagues noted in their study, "To understand and exploit the impact of the gut microbes on human health and well-being it is necessary to decipher the content, diversity and functioning of the microbial gut community."

More than 99 percent of the genes the group found were from bacteria. "These bacteria have functions, which are essential to our health: They synthesize vitamins, break down certain compounds—which cannot be assimilated by our body—[and] play an important role in our immune system," Wang points out.

Inflammatory mutations
As the prevalence of metabolic diseases continues to increase across the U.S. and many other countries, a growing body of research has suggested that some of these physiological changes might have their roots deep in the gut—not in the human cells but some of the many microbes there.

Emory's Gewirtz and his team tracked the gut microbiota in mice as the rodents experienced different kinds of metabolic disorders, such as obesity and insulin resistance. They bred mice with a genetic deficiency (specifically, the absence of Toll-like receptor 5, or TLR5, which has a hand in immune response) to see how it might change their microbial gut communities and metabolic health—and try to understand the order in which the changes were happening. "It's very much appreciated that obesity is associated with insulin resistance and type 2 diabetes," Gewirtz says. But "which comes first is not entirely clear."

Next genetic steps
Although a fuller grasp of microbial genetics promises to boost wellness even further, plenty of big unknowns remain. Scientists are still unsure just how and when these communities of microbes establish themselves in each person's gut. "Everyone is born sterile," Gewirtz says, noting that colonization starts during birth but that they do not know when it reaches relative stability. Regardless of timing, it means that, "the environment is a big, big factor in determining what someone's microbiota will be like," he adds.

If gut microbiota do play a large role in diseases such as obesity and metabolic syndrome, then a recent past change in these communities might help to explain the expansion of patients—and waistlines—in developed countries. "The genetics of humans have not changed appreciably in the last several hundred years," Gewirtz says. "But several changes in the environment have made it so that the gut microbiota is likely considerably different than it was 50 years ago."

Wang and his colleagues are already attempting to track the composition of human gut microbiota back in time to see if this might be the case. But they have their sights set on even bigger collections of genetic data. "Our dream is to build a library" of reference genomes, Wang notes. He hopes to have 10,000 genomes for bacteria within two years. And, he estimated, as soon as more definitive data about these gut genetics emerge, microbial-targeted therapeutics will likely be quick to follow.