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Tag: American Gut project

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This is part 3 of a 4 part series by Katherine H.  Courage. It's a good description of what goes on at a lab that does state of the art genetic analysis of microbes making up the human microbiome (the community of microbes that are part of us). These analyses (especially of fecal samples) are done for the American Gut Project which anyone can participate in (go to americangut.org for more information about this crowd-sourced project). From NPR News:

Behind The Scenes At The Lab That Fingerprints Microbiomes

The gut microbiome may soon reveal important answers to questions about our health. But those answers aren't yet easy to spot or quick to obtain.The week after I mailed off my family's microbial samples to be analyzed for the American Gut Project, I followed them down the road from my home to the University of Colorado, Boulder. They — and I — came to a massive, futuristic science complex there. Daniel McDonald, a doctoral student studying quantitative biology and computer science, greeted me and brought me up to the workspace, where rows of researchers worked on computers outside of a small lab room.

 Inside the lab, where the sealed samples were received, a lone technician sorted through new arrivals, snipping off intentionally fouled swab heads. Each sample kit contains two cotton swabs. One swab head goes directly to the freezers for safe keeping (in case the first sample doesn't provide clear results or for the near future, when sequencing technology is better). The other gets dissolved in a solution so its contents can be carefully analyzed for genetic traces of microbes.

Just down the hall is one of the lab's boxed-in robots, charged with loading samples into individual wells on a tray that will later get fed through the sequencers. The task might seem mundane for such a high-tech tool, but the bot works much faster and more accurately than a human lab helper can.

Still, this is where some of the work can be slow going. The team must wait for hundreds of fecal, oral or skin samples to process together. A single sample could go through the full analysis process in a week, but it would cost thousands of dollars, Rob Knight, a co-founder of the project, estimates, rather than the $99 members of the study pay. For the project to be cost-effective for participants, the research team must wait to collect large groups of samples and analyze them together.

This robot in the Knight lab can handle many samples simultaneously. To avoid contamination, the lab only processes the same kind of samples at the same time together (fecal with fecal, skin with skin and pet with pet). Credit: Katherine Harmon Courage for NPR

Most of the human microbiome is uncharted territory because many of the microbes that live in our guts can't be grown easily in the lab. Oxygen is toxic to them. Using the tools of genetics to probe the human microbiome has already uncovered many new species, each of which has a full genome of its own.

We're still far from getting quick full genomes from each of the inhabitants. Instead, scientists rely on microbes' telltale 16S gene, a marker that helps identify bacteria from one another. Finding the base pairs —the As, Cs, Ts and Gs — for this gene can help scientists sort out which species are present.This is where a nifty machine that performs PCR (polymerase chain reaction) comes in. It makes thousands of copies of the genetic material so that the pattern in the genetic code is easier for the sequencers to find.

These sequencers are located on a lower floor of the building in a room that smells a bit like a photography darkroom. Here, each tray of samples takes about 20 hours to process. On a nearby screen, I see a readout of bright genetic points against a dark background, which looks more like a telescopic image of a night sky than the code to microbial life from someone's stomach.

Deciphering this code is just the first step in understanding what is going on in the jungle of your gut. Like many things in biology, it is not just the organisms present — plants, animals or bacteria — but how these organisms interact that is important.

The dynamics among the characters make a play — not just the cast.For instance, research has shown that many of us are walking around with E. coli in our guts but show no ill effects. In much the same way that weeds or hungry insects might not harm a thriving field or forest but could wreak havoc on an unbalanced ecosystem, we depend on a healthful mix of good microbes to keep the bad ones from taking over.

And to see what our intestinal forests are composed of, we need more than just a few points of genetic data. So after the sequencer spits out the genetic code it has assembled, the data needs to get turned back into intelligible (or at least semi-intelligible) patterns.

To do this, our microbial code gets run through a supercomputer nicknamed Compy, which hums safely in the building's basement beyond two sets of doors and a sticky, dust-collecting floor mat. When I meet her, Compy is busy crunching away on base pairs with her 1,000 processors...The research group is testing using new software to analyze and display these many layers of information.

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In case you missed it, Michael Pollan wrote an article about the human microbiome (the community of microbes that live within us) that was published May 15, 2013. Much of the article was about how the modern western diet may not be good for the human microbiome and how we can eat for better gut health. From the NY Times:

Some of My Best Friends Are Germs 

 As part of a new citizen-science initiative called the American Gut project, the lab sequenced my microbiome — that is, the genes not of “me,” exactly, but of the several hundred microbial species with whom I share this body. These bacteria, which number around 100 trillion, are living (and dying) right now on the surface of my skin, on my tongue and deep in the coils of my intestines, where the largest contingent of them will be found, a pound or two of microbes together forming a vast, largely uncharted interior wilderness that scientists are just beginning to map.

Few of the scientists I interviewed had much doubt that the Western diet was altering our gut microbiome in troubling ways. Some, like Blaser, are concerned about the antimicrobials we’re ingesting with our meals; others with the sterility of processed food. Most agreed that the lack of fiber in the Western diet was deleterious to the microbiome, and still others voiced concerns about the additives in processed foods, few of which have ever been studied for their specific effects on the microbiota.

So I gave up asking scientists for recommendations and began asking them instead how, in light of what they’ve learned about the microbiome, they have changed their own diets and lifestyles. Most of them have made changes. They were slower to take, or give their children, antibiotics. (I should emphasize that in no way is this an argument for the rejection of antibiotics when they are medically called for.) Some spoke of relaxing the sanitary regime in their homes, encouraging their children to play outside in the dirt and with animals — deliberately increasing their exposure to the great patina. Many researchers told me they had eliminated or cut back on processed foods, either because of its lack of fiber or out of concern about additives. In general they seemed to place less faith in probiotics (which few of them used) than in prebiotics — foods likely to encourage the growth of “good bacteria” already present. Several, including Justin Sonnenburg, said they had added fermented foods to their diet: yogurt, kimchi, sauerkraut. These foods can contain large numbers of probiotic bacteria, like L. plantarum and bifidobacteria, and while most probiotic bacteria don’t appear to take up permanent residence in the gut, there is evidence that they might leave their mark on the community, sometimes by changing the gene expression of the permanent residents — in effect turning on or off metabolic pathways within the cell — and sometimes by stimulating or calming the immune response.

...something a gastroenterologist at the University of Pittsburgh told me. “The big problem with the Western diet,” Stephen O’Keefe said, “is that it doesn’t feed the gut, only the upper G I. All the food has been processed to be readily absorbed, leaving nothing for the lower G I. But it turns out that one of the keys to health is fermentation in the large intestine.” And the key to feeding the fermentation in the large intestine is giving it lots of plants with their various types of fiber, including resistant starch (found in bananas, oats, beans); soluble fiber (in onions and other root vegetables, nuts); and insoluble fiber (in whole grains, especially bran, and avocados).

With our diet of swiftly absorbed sugars and fats, we’re eating for one and depriving the trillion of the food they like best: complex carbohydrates and fermentable plant fibers. The byproduct of fermentation is the short-chain fatty acids that nourish the gut barrier and help prevent inflammation. And there are studies suggesting that simply adding plants to a fast-food diet will mitigate its inflammatory effect.

...I began to see how you might begin to shop and cook with the microbiome in mind, the better to feed the fermentation in our guts. The less a food is processed, the more of it that gets safely through the gastrointestinal tract and into the eager clutches of the microbiota. Al dente pasta, for example, feeds the bugs better than soft pasta does; steel-cut oats better than rolled; raw or lightly cooked vegetables offer the bugs more to chomp on than overcooked, etc. This is at once a very old and a very new way of thinking about food: it suggests that all calories are not created equal and that the structure of a food and how it is prepared may matter as much as its nutrient composition.