Tag Archives: Microbiome

Fiber’s Role in Diet

In this post, I discuss the role of the microbiome and the role of fiber in supporting a healthy microbiome. A healthy microbiome is related to the amount and diversity of the bacteria found within it.

If I had to summarize, I would say this: new research strongly confirms that high fiber diets are healthy diets. Because of this finding, eat 20-200 grams of fiber daily, by eating nuts, berries, whole grains, beans and vegetables.

The Role of the Microbiome
Bacteria in the gut – the “microbiome” – has been the subject of intense research interest over the last decade.

We now know that a healthy microbiome is essential to health and wellbeing.

On a scientific level, we now know that a healthy biome is one with billions of bacteria, of many kinds.

And specifically, we now know that a healthy biome has a layer of mucus along the walls of the intestine.

“The gut is coated with a layer of mucus, atop which sits a carpet of hundreds of species of bacteria, part of the human microbiome.”

If that mucus layer is thick, it is healthy. If it is thin, it is unhealthy (thin mucus layers have been linked to chronic inflammation). (“Their intestines got smaller, and its mucus layer thinner. As a result, bacteria wound up much closer to the intestinal wall, and that encroachment triggered an immune reaction.”)

The Role of Fiber in Supporting a Healthy Microbiome
“Fiber” refers to ruffage from fruits, vegetables, and beans that is hard to digest. If fiber is hard to digest, why are they so universally hailed as “good for you”?

That’s the subject of two newly-reported experiments.

The answer seems to lie in bacteria in the gut – the “microbiome”. Much has been written about their beneficial role in the body. But now it seems that some bacteria in the gut have an additional role: they digest fiber that human enzymes cannot digest.

So some bacteria thrive in the gut because of the fiber they eat. And, in an important natural chain, apparently there are some bacteria in the gut that that thrive because the waste of the bacteria that eats fiber. An ecosystem of bacteria tracing to fiber!

This speaks to one of the most-discussed subjects in science today: how and why is one microbiome populated with relatively few bacteria numbers and types, and why is another microbiome much more diverse – with many more bacteria and bacteria types?

One study, shown below, reports from Tanzania, after reviewing data from tribes that sustain themselves on high fiber foods. The results, reported in Science, clearly show that an ultra-high fiber diet results in ultra high bacteria counts and diversity.

Other findings suggest that fiber is the food of many bacteria types. Because of this, a diverse, healthy bacterial microbiome is dependent on a fiber-rich diet. (“On a low-fiber diet, they found, the population crashed, shrinking tenfold.”)

Indeed, it may well be true that many types of fibers support many types of bacteria.

Proof of this?

Researchers, including Dr. Gerwitz at Georgia State proved that more fiber seems to be better:

Bad: high, fat, low fiber (“On a low-fiber diet, they found, the population crashed, shrinking tenfold.” “Many common species became rare, and rare species became common.“)

Good: modest fiber
Better: high dose fiber (“Despite a high-fat diet, the mice had healthy populations of bacteria in their guts, their intestines were closer to normal, and they put on less weight.”)

Best: high dose of fiber-feeding bacteria
(“Once bacteria are done harvesting the energy in dietary fiber, they cast off the fragments as waste. That waste — in the form of short-chain fatty acids — is absorbed by intestinal cells, which use it as fuel.”

(“Research suggests that when bacteria break down dietary fiber down into short-chain fatty acids, some of them pass into the bloodstream and travel to other organs, where they act as signals to quiet down the immune system.”)

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This article documents rich-in-fiber foods:

CREDIT: http://www.todaysdietitian.com/newarchives/063008p28.shtml

In recognition of fiber’s benefits, Today’s Dietitian looks at some of the best ways to boost fiber intake,from whole to fortified foods,using data from the USDA National Nutrient Database for Standard Reference.

Top Fiber-Rich Foods
1. Get on the Bran Wagon (Oat bran, All-bran cereal, fiber-one chewy bars, etc)
One simple way to increase fiber intake is to power up on bran. Bran from many grains is very rich in dietary fiber. Oat bran is high in soluble fiber, which has been shown to lower blood cholesterol levels. Wheat, corn, and rice bran are high in insoluble fiber, which helps prevent constipation. Bran can be sprinkled into your favorite foods,from hot cereal and pancakes to muffins and cookies. Many popular high-fiber cereals and bars are also packed with bran.

2. Take a Trip to Bean Town (Limas, Pintos, Lentils, etc)
Beans really are the magical fruit. They are one of the most naturally rich sources of fiber, as well as protein, lysine, vitamins, and minerals, in the plant kingdom. It’s no wonder so many indigenous diets include a bean or two in the mix. Some people experience intestinal gas and discomfort associated with bean intake, so they may be better off slowly introducing beans into their diet. Encourage a variety of beans as an animal protein replacement in stews, side dishes, salads, soups, casseroles, and dips.

3. Go Berry Picking (especially blackberries and raspberries)
Jewel-like berries are in the spotlight due to their antioxidant power, but let’s not forget about their fiber bonus. Berries happen to yield one of the best fiber-per-calorie bargains on the planet. Since berries are packed with tiny seeds, their fiber content is typically higher than that of many fruits. Clients can enjoy berries year-round by making the most of local berries in the summer and eating frozen, preserved, and dried berries during the other seasons. Berries make great toppings for breakfast cereal, yogurt, salads, and desserts.

4. Wholesome Whole Grains (especially barley, oats, brown rice, rye wafers)
One of the easiest ways to up fiber intake is to focus on whole grains. A grain in nature is essentially the entire seed of the plant made up of the bran, germ, and endosperm. Refining the grain removes the germ and the bran; thus, fiber, protein, and other key nutrients are lost. The Whole Grains Council recognizes a variety of grains and defines whole grains or foods made from them as containing “all the essential parts and naturally-occurring nutrients of the entire grain seed. If the grain has been processed, the food product should deliver approximately the same rich balance of nutrients that are found in the original grain seed.â€‌ Have clients choose different whole grains as features in side dishes, pilafs, salads, breads, crackers, snacks, and desserts.

5. Sweet Peas (especially frozen green peas, black eyed peas)
Peas,from fresh green peas to dried peas,are naturally chock full of fiber. In fact, food technologists have been studying pea fiber as a functional food ingredient. Clients can make the most of peas by using fresh or frozen green peas and dried peas in soups, stews, side dishes, casseroles, salads, and dips.

6. Green, the Color of Fiber (Spinach, etc)
Deep green, leafy vegetables are notoriously rich in beta-carotene, vitamins, and minerals, but their fiber content isn’t too shabby either. There are more than 1,000 species of plants with edible leaves, many with similar nutritional attributes, including high-fiber content. While many leafy greens are fabulous tossed in salads, saut ©ing them in olive oil, garlic, lemon, and herbs brings out a rich flavor.

7. Squirrel Away Nuts and Seeds (especially flaxseed and sesame seed)
Go nuts to pack a fiber punch. One ounce of nuts and seeds can provide a hearty contribution to the day’s fiber recommendation, along with a bonus of healthy fats, protein, and phytochemicals. Sprinkling a handful of nuts or seeds over breakfast cereals, yogurt, salads, and desserts is a tasty way to do fiber.

8. Play Squash (especially acorn squash)
Dishing up squash,from summer to winter squash,all year is another way that clients can ratchet up their fiber intake. These nutritious gems are part of the gourd family and contribute a variety of flavors, textures, and colors, as well as fiber, vitamins, minerals, and carotenoids, to the dinner plate. Squash can be turned into soups, stews, side dishes, casseroles, salads, and crudit ©s. Brush squash with olive oil and grill it in the summertime for a healthy, flavorful accompaniment to grilled meats.

9. Brassica or Bust (broccoli, cauliflower, kale, cabbage, and Brussels sprouts)
Brassica vegetables have been studied for their cancer-protective effects associated with high levels of glucosinolates. But these brassy beauties, including broccoli, cauliflower, kale, cabbage, and Brussels sprouts, are also full of fiber. They can be enjoyed in stir-fries, casseroles, soups, and salads and steamed as a side dish.

10. Hot Potatoes
The humble spud, the top vegetable crop in the world, is plump with fiber. Since potatoes are so popular in America, they’re an easy way to help pump up people’s fiber potential. Why stop at Russets? There are numerous potatoes that can provide a rainbow of colors, nutrients, and flavors, and remind clients to eat the skins to reap the greatest fiber rewards. Try adding cooked potatoes with skins to salads, stews, soups, side dishes, stir-fries, and casseroles or simply enjoy baked potatoes more often.

11. Everyday Fruit Basket (especially pears and oranges)
Look no further than everyday fruits to realize your full fiber potential. Many are naturally packed with fiber, as well as other important vitamins and minerals. Maybe the doctor was right when he advised an apple a day, but he could have added pears, oranges, and bananas to the prescription as well. When between fruit seasons, clients can rely on dried fruits to further fortify their diet. Encourage including fruit at breakfast each morning instead of juice; mixing dried fruits into cereals, yogurts, and salads; and reaching for the fruit bowl at snack time. It’s a healthy habit all the way around.

12. Exotic Destinations (especially avocado)
Some of the plants with the highest fiber content in the world may be slightly out of your clients’ comfort zone and, for that matter, time zone. A rainbow of indigenous fruits and vegetables used in cultural food traditions around the globe are very high in fiber. Entice clients to introduce a few new plant foods into their diets to push up the flavor, as well as their fiber, quotient.

13. Fiber Fortification Power
More foods,from juice to yogurt,are including fiber fortification in their ingredient lineup. Such foods may help busy people achieve their fiber goals. As consumer interest in foods with functional benefits, such as digestive health and cardiovascular protection, continues to grow, expect to see an even greater supply of food products promoting fiber content on supermarket shelves.

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This article documents the newly-reported experiments:

CREDIT: NYT Article on Fiber Science

Fiber is Good for You. Now we Know Why

By Carl Zimmer
Jan. 1, 2018
A diet of fiber-rich foods, such as fruits and vegetables, reduces the risk of developing diabetes, heart disease and arthritis. Indeed, the evidence for fiber’s benefits extends beyond any particular ailment: Eating more fiber seems to lower people’s mortality rate, whatever the cause.

That’s why experts are always saying how good dietary fiber is for us. But while the benefits are clear, it’s not so clear why fiber is so great. “It’s an easy question to ask and a hard one to really answer,” said Fredrik Bäckhed, a biologist at the University of Gothenburg in Sweden.

He and other scientists are running experiments that are yielding some important new clues about fiber’s role in human health. Their research indicates that fiber doesn’t deliver many of its benefits directly to our bodies.

Instead, the fiber we eat feeds billions of bacteria in our guts. Keeping them happy means our intestines and immune systems remain in good working order.

In order to digest food, we need to bathe it in enzymes that break down its molecules. Those molecular fragments then pass through the gut wall and are absorbed in our intestines.
But our bodies make a limited range of enzymes, so that we cannot break down many of the tough compounds in plants. The term “dietary fiber” refers to those indigestible molecules.

But they are indigestible only to us. The gut is coated with a layer of mucus, atop which sits a carpet of hundreds of species of bacteria, part of the human microbiome. Some of these microbes carry the enzymes needed to break down various kinds of dietary fiber.

The ability of these bacteria to survive on fiber we can’t digest ourselves has led many experts to wonder if the microbes are somehow involved in the benefits of the fruits-and-vegetables diet. Two detailed studies published recently in the journal Cell Host and Microbe provide compelling evidence that the answer is yes.

In one experiment, Andrew T. Gewirtz of Georgia State University and his colleagues put mice on a low-fiber, high-fat diet. By examining fragments of bacterial DNA in the animals’ feces, the scientists were able to estimate the size of the gut bacterial population in each mouse.

On a low-fiber diet, they found, the population crashed, shrinking tenfold.

Dr. Bäckhed and his colleagues carried out a similar experiment, surveying the microbiome in mice as they were switched from fiber-rich food to a low-fiber diet. “It’s basically what you’d get at McDonald’s,” said Dr. Bäckhed said. “A lot of lard, a lot of sugar, and twenty percent protein.”

The scientists focused on the diversity of species that make up the mouse’s gut microbiome. Shifting the animals to a low-fiber diet had a dramatic effect, they found: Many common species became rare, and rare species became common.

Along with changes to the microbiome, both teams also observed rapid changes to the mice themselves. Their intestines got smaller, and its mucus layer thinner. As a result, bacteria wound up much closer to the intestinal wall, and that encroachment triggered an immune reaction.

After a few days on the low-fiber diet, mouse intestines developed chronic inflammation. After a few weeks, Dr. Gewirtz’s team observed that the mice began to change in other ways, putting on fat, for example, and developing higher blood sugar levels.

Dr. Bäckhed and his colleagues also fed another group of rodents the high-fat menu, along with a modest dose of a type of fiber called inulin. The mucus layer in their guts was healthier than in mice that didn’t get fiber, the scientists found, and intestinal bacteria were kept at a safer distance from their intestinal wall.

Dr. Gewirtz and his colleagues gave inulin to their mice as well, but at a much higher dose. The improvements were even more dramatic: Despite a high-fat diet, the mice had healthy populations of bacteria in their guts, their intestines were closer to normal, and they put on less weight.

Dr. Bäckhed and his colleagues ran one more interesting experiment: They spiked water given to mice on a high-fat diet with a species of fiber-feeding bacteria. The addition changed the mice for the better: Even on a high-fat diet, they produced more mucus in their guts, creating a healthy barrier to keep bacteria from the intestinal walls.

One way that fiber benefits health is by giving us, indirectly, another source of food, Dr. Gewirtz said. Once bacteria are done harvesting the energy in dietary fiber, they cast off the fragments as waste. That waste — in the form of short-chain fatty acids — is absorbed by intestinal cells, which use it as fuel.

But the gut’s microbes do more than just make energy. They also send messages. Intestinal cells rely on chemical signals from the bacteria to work properly, Dr. Gewirtz said. The cells respond to the signals by multiplying and making a healthy supply of mucus. They also release bacteria-killing molecules.
By generating these responses, gut bacteria help maintain a peaceful coexistence with the immune system. They rest atop the gut’s mucus layer at a safe distance from the intestinal wall. Any bacteria that wind up too close get wiped out by antimicrobial poisons.

While some species of gut bacteria feed directly on dietary fiber, they probably support other species that feed on their waste. A number of species in this ecosystem — all of it built on fiber — may be talking to our guts.

Going on a low-fiber diet disturbs this peaceful relationship, the new studies suggest. The species that depend on dietary fiber starve, as do the other species that depend on them. Some species may switch to feeding on the host’s own mucus.

With less fuel, intestinal cells grow more slowly. And without a steady stream of chemical signals from bacteria, the cells slow their production of mucus and bacteria-killing poisons.
As a result, bacteria edge closer to the intestinal wall, and the immune system kicks into high gear.

“The gut is always precariously balanced between trying to contain these organisms and not to overreact,” said Eric C. Martens, a microbiologist at the University of Michigan who was not involved in the new studies. “It could be a tipping point between health and disease.”

Inflammation can help fight infections, but if it becomes chronic, it can harm our bodies. Among other things, chronic inflammation may interfere with how the body uses the calories in food, storing more of it as fat rather than burning it for energy.

Justin L. Sonnenburg, a biologist at Stanford University who was not involved in the new studies, said that a low-fiber diet can cause low-level inflammation not only in the gut, but throughout the body.

His research suggests that when bacteria break down dietary fiber down into short-chain fatty acids, some of them pass into the bloodstream and travel to other organs, where they act as signals to quiet down the immune system.

“You can modulate what’s happening in your lung based on what you’re feeding your microbiome in your gut,” Dr. Sonnenburg said.
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Hannah D. Holscher, a nutrition scientist at the University of Illinois who was not involved in the new studies, said that the results on mice need to be put to the test in humans. But it’s much harder to run such studies on people.

In her own lab, Dr. Holscher acts as a round-the-clock personal chef. She and her colleagues provide volunteers with all their meals for two weeks. She can then give some of her volunteers an extra source of fiber — such as walnuts — and look for changes in both their microbiome and their levels of inflammation.

Dr. Holscher and other researchers hope that they will learn enough about how fiber influences the microbiome to use it as a way to treat disorders. Lowering inflammation with fiber may also help in the treatment of immune disorders such as inflammatory bowel disease.

Fiber may also help reverse obesity. Last month in the American Journal of Clinical Nutrition, Dr. Holscher and her colleagues reviewed a number of trials in which fiber was used to treat obesity. They found that fiber supplements helped obese people to lose about five pounds, on average.
But for those who want to stay healthy, simply adding one kind of fiber to a typical Western diet won’t be a panacea. Giving mice inulin in the new studies only partly restored them to health.

That’s probably because we depend on a number of different kinds of dietary fiber we get from plants. It’s possible that each type of fiber feeds a particular set of bacteria, which send their own important signals to our bodies.

“It points to the boring thing that we all know but no one does,” Dr. Bäckhed said. “If you eat more green veggies and less fries and sweets, you’ll probably be better off in the long term.”

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CREDIT: https://www.npr.org/sections/goatsandsoda/2017/08/24/545631521/is-the-secret-to-a-healthier-microbiome-hidden-in-the-hadza-diet

Is The Secret To A Healthier Microbiome Hidden In The Hadza Diet?

August 24, 20176:11 PM ET
Heard on All Things Considered

MICHAELEEN DOUCLEFF
Twitter

Enlarge this image

The words “endangered species” often conjure up images of big exotic creatures. Think elephants, leopards and polar bears.

But there’s another of type of extinction that may be occurring, right now, inside our bodies.

Yes, I’m talking about the microbiome — that collection of bacteria in our intestines that influences everything from metabolism and the immune system to moods and behavior.

For the past few years, scientists around the world have been accumulating evidence that the Western lifestyle is altering our microbiome. Some species of bacteria are even disappearing to undetectable levels.

“Over time we are losing valuable members of our community,” says Justin Sonnenburg, a microbiologist at Stanford University, who has been studying the microbiome for more than a decade.

Now Sonnenburg and his team have evidence for why this microbial die-off is happening — and hints about what we can possibly do to reverse it.

The study, published Thursday in the journal Science, focuses on a group of hunter-gatherers in Tanzania, called Hadza.
Their diet consists almost entirely of food they find in the forest, including wild berries, fiber-rich tubers, honey and wild meat. They basically eat no processed food — or even food that comes from farms.
“They are a very special group of people,” Sonnenburg says. “There are only about 2,200 left and really only about 200 that exclusively adhere to hunting and gathering.”

Sonnenberg and his colleagues analyzed 350 stool samples from Hadza people taken over the course of about a year. They then compared the bacteria found in Hadza with those found in 17 other cultures around the world, including other hunter-gatherer communities in Venezuela and Peru and subsistence farmers in Malawi and Cameroon.

The trend was clear: The further away people’s diets are from a Western diet, the greater the variety of microbes they tend to have in their guts. And that includes bacteria that are missing from American guts.

“So whether it’s people in Africa, Papua New Guinea or South America, communities that live a traditional lifestyle have common gut microbes — ones that we all lack in the industrialized world,” Sonnenburg says.

In a way, the Western diet — low in fiber and high in refined sugars — is basically wiping out species of bacteria from our intestines.

That’s the conclusion Sonnenburg and his team reached after analyzing the Hadza microbiome at one stage of the yearlong study. But when they checked several months later, they uncovered a surprising twist: The composition of the microbiome fluctuated over time, depending on the season and what people were eating. And at one point, the composition started to look surprisingly similar to that of Westerners’ microbiome.

During the dry season, Hadza eat a lot of more meat — kind of like Westerners do. And their microbiome shifted as their diet changed. Some of the bacterial species that had been prevalent disappeared to undetectable levels, similar to what’s been observed in Westerners’ guts.

But then in wet season — when Hadza eat more berries and honey — these missing microbes returned, although the researchers are not really sure what’s in these foods that bring the microbes back.

“I think this finding is really exciting,” says Lawrence David, who studies the microbiome at Duke University. “It suggests the shifts in the microbiome seen in industrialized nations might not be permanent — that they might be reversible by changes in people’s diets.

“The finding supports the idea that the microbiome is plastic, depending on diet,” David adds.

Now the big question is: What’s the key dietary change that could bring the missing microbes back?

Lawrence thinks it could be cutting down on fat. “At a high level, it sounds like that,” he says, “because what changed in the Hadza’s diet was whether or not they were hunting versus foraging for berries or honey,” he says.

But Sonnenburg is placing his bets on another dietary component: fiber — which is a vital food for the microbiome.
“We’re beginning to realize that people who eat more dietary fiber are actually feeding their gut microbiome,”
Sonnenburg says.

Hadza consume a huge amount of fiber because throughout the year, they eat fiber-rich tubers and fruit from baobab trees. These staples give them about 100 to 150 grams of fiber each day. That’s equivalent to the fiber in 50 bowls of Cheerios — and 10 times more than many Americans eat.

“Over the past few years, we’ve come to realize how important this gut community is for our health, and yet we’re eating a low-fiber diet that totally neglects them,” he says. “So we’re essentially starving our microbial selves.”

Microbiome Apps Personalize EAT recommendations

Richard Sprague provides a useful update about the microbiome landscape below. Microbiome is exploding. Your gut can be measured, and your gut can influence your health and well-being. But now …. these gut measurements can offer people a first: personalized nutrition information.

Among the more relevant points:

– Israel’s Weitzman Institute is the global leader academically. Eran Elinav, a physician and immunologist at the Weizmann Institute and one of their lead investigators (see prior post).
– The older technology for measuring the gut is called “16S” sequencing. It tell you at a high level which kinds of microbes are present. It’s cheap and easy, but 16S can see only broad categories,
– The companies competing to measure your microbiome are uBiome, American Gut, Thryve, DayTwo and Viome. DayTwo and Viome offer more advanced technology (see below).
– The latest technology seems to be “metagenomic sequencing”. It is better because it is more specific and detailed.
– By combining “metagenomic sequencing” information with extensive research about how certain species interact with particular foods, machine-learning algorithms can recommend what you should eat.
– DayTwo offers a metagenomic sequencing for $299, and then combines that with all available research to offer personalized nutrition information.
– DayTwo recently completed a $12 million financing round from, among others, Mayo Clinic, which announced it would be validating the research in the U.S.
– DayTwo draws its academic understandings from Israel’s Weitzman Institute. The app is based on more than five years of highly cited research showing, for example, that while people on average respond similarly to white bread versus whole grain sourdough bread, the differences between individuals can be huge: what’s good for one specific person may be bad for another.

CREDIT: Article on Microbiome Advances

When a Double-Chocolate Brownie is Better for You Than Quinoa

A $299 microbiome test from DayTwo turns up some counterintuitive dietary advice.

Why do certain diets work well for some people but not others? Although several genetic tests try to answer that question and might help you craft ideal nutrition plans, your DNA reveals only part of the picture. A new generation of tests from DayTwo and Viome offer diet advice based on a more complete view: they look at your microbiome, the invisible world of bacteria that help you metabolize food, and, unlike your DNA, change constantly throughout your life.
These bugs are involved in the synthesis of vitamins and other compounds in food, and they even play a role in the digestion of gluten. Artificial sweeteners may not contain calories, but they do modify the bacteria in your gut, which may explain why some people continue to gain weight on diet soda. Everyone’s microbiome is different.

So how well do these new tests work?
Basic microbiome tests, long available from uBiome, American Gut, Thryve, and others, based on older “16S” sequencing, can tell you at a high level which kinds of microbes are present. It’s cheap and easy, but 16S can see only broad categories, the bacterial equivalent of, say, canines versus felines. But just as your life might depend on knowing the difference between a wolf and a Chihuahua, your body’s reaction to food often depends on distinctions that can be known only at the species level. The difference between a “good” microbe and a pathogen can be a single DNA base pair.

New tests use more precise “metagenomic” sequencing that can make those distinctions. And by combining that information with extensive research about how those species interact with particular foods, machine-learning algorithms can recommend what you should eat. (Disclosure: I am a former “citizen scientist in residence” at uBiome. But I have no current relationship with any of these companies; I’m just an enthusiast about the microbiome.)

I recently tested myself with DayTwo ($299) to see what it would recommend for me, and I was pleased that the advice was not always the standard “eat more vegetables” that you’ll get from other products claiming to help you eat healthily. DayTwo’s advice is much more specific and often refreshingly counterintuitive. It’s based on more than five years of highly cited research at Israel’s Weizmann Institute, showing, for example, that while people on average respond similarly to white bread versus whole grain sourdough bread, the differences between individuals can be huge: what’s good for one specific person may be bad for another.

In my case, whole grain breads all rate C-. French toast with challah bread: A.

The DayTwo test was pretty straightforward: you collect what comes out of your, ahem, gut, which involves mailing a sample from your time on the toilet. Unlike the other tests, which can analyze the DNA found in just a tiny swab from a stain on a piece of toilet paper, DayTwo requires more like a tablespoon. The extra amount is needed for DayTwo’s more comprehensive metagenomics sequencing.

Since you can get a microbiome test from other companies for under $100, does the additional metagenomic information from DayTwo justify its much higher price? Generally, I found the answer is yes.

About two months after I sent my sample, my iPhone lit up with my results in a handy app that gave me a personalized rating for most common foods, graded from A+ to C-. In my case, whole grain breads all rate C-. Slightly better are pasta and oatmeal, each ranked C+. Even “healthy” quinoa — a favorite of gluten-free diets — was a mere B-. Why? DayTwo’s algorithm can’t say precisely, but among the hundreds of thousands of gut microbe and meal combinations it was trained on, it finds that my microbiome doesn’t work well with these grains. They make my blood sugar rise too high.

So what kinds of bread are good for me? How about a butter croissant (B+) or cheese ravioli (A-)? The ultimate bread winner for me: French toast with challah bread (A). These recommendations are very different from the one-size-fits-all advice from the U.S. Department of Agriculture or the American Diabetes Association.

I was also pleased to learn that a Starbucks double chocolate brownie is an A- for me, while a 100-calorie pack of Snyder’s of Hanover pretzels gets a C-. That might go against general diet advice, but an algorithm determined that the thousands of bacterial species inside me tend to metabolize fatty foods in a way that results in healthier blood sugar levels than what I get from high-carb foods. Of course, that’s advice just for me; your mileage may vary.

Although the research behind DayTwo has been well-reviewed for more than five years, the app is new to the U.S., so the built-in food suggestions often seem skewed toward Middle Eastern eaters, perhaps the Israeli subjects who formed the original research cohort. That might explain why the app’s suggestions for me include lamb souvlaki with yogurt garlic dip for dinner (A+) and lamb kabob and a side of lentils (A) for lunch. They sound delicious, but to many American ears they might not have the ring of “pork ribs” or “ribeye steak,” which have the same A+ rating. Incidentally, DayTwo recently completed a $12 million financing round from, among others, Mayo Clinic, which announced it would be validating the research in the U.S., so I expect the menu to expand with more familiar fare.

Fortunately you’re not limited to the built-in menu choices. The app includes a “build a meal” function that lets you enter combinations of foods from a large database that includes packaged items from Trader Joe’s and Whole Foods.

There is much more to the product, such as a graphical rendering of where my microbiome fits on the spectrum of the rest of the population that eats a particular food. Since the microbiome changes constantly, this will help me see what is different when I do a retest and when I try Viome and other tests.

I’ve had my DayTwo results for only a few weeks, so it’s too soon to know what happens if I take the app’s advice over the long term. Thankfully I’m in good health and reasonably fit, but for now I’ll be eating more strawberries (A+) and blackberries (A-), and fewer apples (B-) and bananas (C+). And overall I’m looking forward to a future where each of us will insist on personalized nutritional information. We all have unique microbiomes, and an app like DayTwo lets us finally eat that way too.

Richard Sprague is a technology executive and quantified-self enthusiast who has worked at Apple, Microsoft, and other tech companies. He is now the U.S. CEO of an AI healthcare startup, Airdoc.

====================APPENDIX: Older Posts about the microbiome =========

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“Arivale” Launched and Moving Fast. They launched last month. They have 19 people in the Company and a 107 person pilot – but their plans are way more ambitious than that. Moreover: “The founders said they couldn’t envision Arivale launching even two or three years ago.” Read on …. This is an important development: the […]

Precision Wellness at Mt Sinai
My Sinai announcement Mount Sinai to Establish Precision Wellness Center to Advance Personalized Healthcare Mount Sinai Health System Launches Telehealth Initiatives Joshua Harris, co-Founder of Apollo Global Management, and his wife, Marjorie has made a $5 million gift to the Icahn School of Medicine at Mount Sinai to establish the Harris Center for Precision Wellness. […]

Proteomics
“Systems biology…is about putting together rather than taking apart, integration rather than reduction. It requires that we develop ways of thinking about integration that are as rigorous as our reductionist programmes, but different….It means changing our philosophy, in the full sense of the term” (Denis Noble).[5] Proteomics From Wikipedia, the free encyclopedia For the journal […]

Microbiome Update

CREDIT: https://www.wsj.com/articles/how-disrupting-your-guts-rhythm-affects-your-health-1488164400?mod=e2tw

A healthy community of microbes in the gut maintains regular daily cycles of activities.
A healthy community of microbes in the gut maintains regular daily cycles of activities.PHOTO: WEIZMANN INSTITUTE
By LARRY M. GREENBERG
Updated Feb. 27, 2017 3:33 p.m. ET
4 COMMENTS
New research is helping to unravel the mystery of how disruptions to the bacteria in our gut, caused by an unhealthy diet or irregular sleep, can lead to a number of diseases.

Such research could someday result in new treatments for obesity, diabetes and other metabolic conditions by restoring the health of the gut-microbe community, known as the microbiota. Researchers are exploring how to do this through individualized diets and mealtimes or other interventions.

When gut microbiota are healthy, they maintain regular daily cycles of activities such as congregating in different parts of the intestine and producing metabolites, molecules that help the body function properly. A disruption of the gut’s circadian rhythms is communicated through the bloodstream and upsets many of the body’s other circadian clocks, especially in the liver, one of the main metabolic organs, according to a studyby Israel’s Weizmann Institute of Science published in the journal Cell in December.

The gut’s circadian rhythms and those in other organs “dance together in a very profound way and go up and down in coordination with each other,” says Eran Elinav, a physician and immunologist at the Weizmann Institute and one of the study’s lead investigators. “By controlling the gut microbiota, you can modify many physiological capabilities” throughout the body, he says.

Microbiome Update

My last research on this subject was in August, 2014. I looked at both microbiomes and proteomics.

Today, the New York Times published a very comprehensive update on microbiome research:

Link to New York Time Microbiome Article

Here is the article itself:

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Can the Bacteria in Your Gut Explain Your Mood?
The rich array of microbiota in our intestines can tell us more than you might think.

By PETER ANDREY SMITH
JUNE 23, 2015

Eighteen vials were rocking back and forth on a squeaky mechanical device the shape of a butcher scale, and Mark Lyte was beside himself with excitement. ‘‘We actually got some fresh yesterday — freshly frozen,’’ Lyte said to a lab technician. Each vial contained a tiny nugget of monkey feces that were collected at the Harlow primate lab near Madison, Wis., the day before and shipped to Lyte’s lab on the Texas Tech University Health Sciences Center campus in Abilene, Tex.

Lyte’s interest was not in the feces per se but in the hidden form of life they harbor. The digestive tube of a monkey, like that of all vertebrates, contains vast quantities of what biologists call gut microbiota. The genetic material of these trillions of microbes, as well as others living elsewhere in and on the body, is collectively known as the microbiome. Taken together, these bacteria can weigh as much as six pounds, and they make up a sort of organ whose functions have only begun to reveal themselves to science. Lyte has spent his career trying to prove that gut microbes communicate with the nervous system using some of the same neurochemicals that relay messages in the brain.
Inside a closet-size room at his lab that afternoon, Lyte hunched over to inspect the vials, whose samples had been spun down in a centrifuge to a radiant, golden broth. Lyte, 60, spoke fast and emphatically. ‘‘You wouldn’t believe what we’re extracting out of poop,’’ he told me. ‘‘We found that the guys here in the gut make neurochemicals. We didn’t know that. Now, if they make this stuff here, does it have an influence there? Guess what? We make the same stuff. Maybe all this communication has an influence on our behavior.’’

Since 2007, when scientists announced plans for a Human Microbiome Project to catalog the micro-organisms living in our body, the profound appreciation for the influence of such organisms has grown rapidly with each passing year. Bacteria in the gut produce vitamins and break down our food; their presence or absence has been linked to obesity, inflammatory bowel disease and the toxic side effects of prescription drugs. Biologists now believe that much of what makes us human depends on microbial activity. The two million unique bacterial genes found in each human microbiome can make the 23,000 genes in our cells seem paltry, almost negligible, by comparison. ‘‘It has enormous implications for the sense of self,’’ Tom Insel, the director of the National Institute of Mental Health, told me. ‘‘We are, at least from the standpoint of DNA, more microbial than human. That’s a phenomenal insight and one that we have to take seriously when we think about human development.’’

Given the extent to which bacteria are now understood to influence human physiology, it is hardly surprising that scientists have turned their attention to how bacteria might affect the brain. Micro-organisms in our gut secrete a profound number of chemicals, and researchers like Lyte have found that among those chemicals are the same substances used by our neurons to communicate and regulate mood, like dopamine, serotonin and gamma-aminobutyric acid (GABA). These, in turn, appear to play a function in intestinal disorders, which coincide with high levels of major depression and anxiety. Last year, for example, a group in Norway examined feces from 55 people and found certain bacteria were more likely to be associated with depressive patients.

At the time of my visit to Lyte’s lab, he was nearly six months into an experiment that he hoped would better establish how certain gut microbes influenced the brain, functioning, in effect, as psychiatric drugs. He was currently compiling a list of the psychoactive compounds found in the feces of infant monkeys. Once that was established, he planned to transfer the microbes found in one newborn monkey’s feces into another’s intestine, so that the recipient would end up with a completely new set of microbes — and, if all went as predicted, change their neurodevelopment. The experiment reflected an intriguing hypothesis. Anxiety, depression and several pediatric disorders, including autism and hyperactivity, have been linked with gastrointestinal abnormalities. Microbial transplants were not invasive brain surgery, and that was the point: Changing a patient’s bacteria might be difficult but it still seemed more straightforward than altering his genes.

When Lyte began his work on the link between microbes and the brain three decades ago, it was dismissed as a curiosity. By contrast, last September, the National Institute of Mental Health awarded four grants worth up to $1 million each to spur new research on the gut microbiome’s role in mental disorders, affirming the legitimacy of a field that had long struggled to attract serious scientific credibility. Lyte and one of his longtime colleagues, Christopher Coe, at the Harlow primate lab, received one of the four. ‘‘What Mark proposed going back almost 25 years now has come to fruition,’’ Coe told me. ‘‘Now what we’re struggling to do is to figure out the logic of it.’’ It seems plausible, if not yet proved, that we might one day use microbes to diagnose neurodevelopmental disorders, treat mental illnesses and perhaps even fix them in the brain.

In 2011, a team of researchers at University College Cork, in Ireland, and McMaster University, in Ontario, published a study in Proceedings of the National Academy of Science that has become one of the best-known experiments linking bacteria in the gut to the brain. Laboratory mice were dropped into tall, cylindrical columns of water in what is known as a forced-swim test, which measures over six minutes how long the mice swim before they realize that they can neither touch the bottom nor climb out, and instead collapse into a forlorn float. Researchers use the amount of time a mouse floats as a way to measure what they call ‘‘behavioral despair.’’ (Antidepressant drugs, like Zoloft and Prozac, were initially tested using this forced-swim test.)

For several weeks, the team, led by John Cryan, the neuroscientist who designed the study, fed a small group of healthy rodents a broth infused with Lactobacillus rhamnosus, a common bacterium that is found in humans and also used to ferment milk into probiotic yogurt. Lactobacilli are one of the dominant organisms babies ingest as they pass through the birth canal. Recent studies have shown that mice stressed during pregnancy pass on lowered levels of the bacterium to their pups. This type of bacteria is known to release immense quantities of GABA; as an inhibitory neurotransmitter, GABA calms nervous activity, which explains why the most common anti-anxiety drugs, like Valium and Xanax, work by targeting GABA receptors.

Cryan found that the mice that had been fed the bacteria-laden broth kept swimming longer and spent less time in a state of immobilized woe. ‘‘They behaved as if they were on Prozac,’’ he said. ‘‘They were more chilled out and more relaxed.’’ The results suggested that the bacteria were somehow altering the neural chemistry of mice.

Until he joined his colleagues at Cork 10 years ago, Cryan thought about microbiology in terms of pathology: the neurological damage created by diseases like syphilis or H.I.V. ‘‘There are certain fields that just don’t seem to interact well,’’ he said. ‘‘Microbiology and neuroscience, as whole disciplines, don’t tend to have had much interaction, largely because the brain is somewhat protected.’’ He was referring to the fact that the brain is anatomically isolated, guarded by a blood-brain barrier that allows nutrients in but keeps out pathogens and inflammation, the immune system’s typical response to germs. Cryan’s study added to the growing evidence that signals from beneficial bacteria nonetheless find a way through the barrier. Somehow — though his 2011 paper could not pinpoint exactly how — micro-organisms in the gut tickle a sensory nerve ending in the fingerlike protrusion lining the intestine and carry that electrical impulse up the vagus nerve and into the deep-brain structures thought to be responsible for elemental emotions like anxiety. Soon after that, Cryan and a co-author, Ted Dinan, published a theory paper in Biological Psychiatry calling these potentially mind-altering microbes ‘‘psychobiotics.’’
It has long been known that much of our supply of neurochemicals — an estimated 50 percent of the dopamine, for example, and a vast majority of the serotonin — originate in the intestine, where these chemical signals regulate appetite, feelings of fullness and digestion. But only in recent years has mainstream psychiatric research given serious consideration to the role microbes might play in creating those chemicals. Lyte’s own interest in the question dates back to his time as a postdoctoral fellow at the University of Pittsburgh in 1985, when he found himself immersed in an emerging field with an unwieldy name: psychoneuroimmunology, or PNI, for short. The central theory, quite controversial at the time, suggested that stress worsened disease by suppressing our immune system.

By 1990, at a lab in Mankato, Minn., Lyte distilled the theory into three words, which he wrote on a chalkboard in his office: Stress->Immune->Disease. In the course of several experiments, he homed in on a paradox. When he dropped an intruder mouse in the cage of an animal that lived alone, the intruder ramped up its immune system — a boost, he suspected, intended to fight off germ-ridden bites or scratches. Surprisingly, though, this did not stop infections. It instead had the opposite effect: Stressed animals got sick. Lyte walked up to the board and scratched a line through the word ‘‘Immune.’’ Stress, he suspected, directly affected the bacterial bugs that caused infections.

To test how micro-organisms reacted to stress, he filled petri plates with a bovine-serum-based medium and laced the dishes with a strain of bacterium. In some, he dropped norepinephrine, a neurochemical that mammals produce when stressed. The next day, he snapped a Polaroid. The results were visible and obvious: The control plates were nearly barren, but those with the norepinephrine bloomed with bacteria that filigreed in frostlike patterns. Bacteria clearly responded to stress.

Then, to see if bacteria could induce stress, Lyte fed white mice a liquid solution of Campylobacter jejuni, a bacterium that can cause food poisoning in humans but generally doesn’t prompt an immune response in mice. To the trained eye, his treated mice were as healthy as the controls. But when he ran them through a plexiglass maze raised several feet above the lab floor, the bacteria-fed mice were less likely to venture out on the high, unprotected ledges of the maze. In human terms, they seemed anxious. Without the bacteria, they walked the narrow, elevated planks.

Each of these results was fascinating, but Lyte had a difficult time finding microbiology journals that would publish either. ‘‘It was so anathema to them,’’ he told me. When the mouse study finally appeared in the journal Physiology & Behavior in 1998, it garnered little attention. And yet as Stephen Collins, a gastroenterologist at McMaster University, told me, those first papers contained the seeds of an entire new field of research. ‘‘Mark showed, quite clearly, in elegant studies that are not often cited, that introducing a pathological bacterium into the gut will cause a change in behavior.’’

Lyte went on to show how stressful conditions for newborn cattle worsened deadly E. coli infections. In another experiment, he fed mice lean ground hamburger that appeared to improve memory and learning — a conceptual proof that by changing diet, he could change gut microbes and change behavior. After accumulating nearly a decade’s worth of evidence, in July 2008, he flew to Washington to present his research. He was a finalist for the National Institutes of Health’s Pioneer Award, a $2.5 million grant for so-called blue-sky biomedical research. Finally, it seemed, his time had come. When he got up to speak, Lyte described a dialogue between the bacterial organ and our central nervous system. At the two-minute mark, a prominent scientist in the audience did a spit take.

‘‘Dr. Lyte,’’ he later asked at a question-and-answer session, ‘‘if what you’re saying is right, then why is it when we give antibiotics to patients to kill bacteria, they are not running around crazy on the wards?’’

Lyte knew it was a dismissive question. And when he lost out on the grant, it confirmed to him that the scientific community was still unwilling to imagine that any part of our neural circuitry could be influenced by single-celled organisms. Lyte published his theory in Medical Hypotheses, a low-ranking journal that served as a forum for unconventional ideas. The response, predictably, was underwhelming. ‘‘I had people call me crazy,’’ he said.

But by 2011 — when he published a second theory paper in Bioessays, proposing that probiotic bacteria could be tailored to treat specific psychological diseases — the scientific community had become much more receptive to the idea. A Canadian team, led by Stephen Collins, had demonstrated that antibiotics could be linked to less cautious behavior in mice, and only a few months before Lyte, Sven Pettersson, a microbiologist at the Karolinska Institute in Stockholm, published a landmark paper in Proceedings of the National Academy of Science that showed that mice raised without microbes spent far more time running around outside than healthy mice in a control group; without the microbes, the mice showed less apparent anxiety and were more daring. In Ireland, Cryan published his forced-swim-test study on psychobiotics. There was now a groundswell of new research. In short order, an implausible idea had become a hypothesis in need of serious validation.

Late last year, Sarkis Mazmanian, a microbiologist at the California Institute of Technology, gave a presentation at the Society for Neuroscience, ‘‘Gut Microbes and the Brain: Paradigm Shift in Neuroscience.’’ Someone had inadvertently dropped a question mark from the end, so the speculation appeared to be a definitive statement of fact. But if anyone has a chance of delivering on that promise, it’s Mazmanian, whose research has moved beyond the basic neurochemicals to focus on a broader class of molecules called metabolites: small, equally druglike chemicals that are produced by micro-organisms. Using high-powered computational tools, he also hopes to move beyond the suggestive correlations that have typified psychobiotic research to date, and instead make decisive discoveries about the mechanisms by which microbes affect brain function.

Two years ago, Mazmanian published a study in the journal Cell with Elaine Hsiao, then a graduate student at his lab and now a neuroscientist at Caltech, that made a provocative link between a single molecule and behavior. Their research found that mice exhibiting abnormal communication and repetitive behaviors, like obsessively burying marbles, were mollified when they were given one of two strains of the bacterium Bacteroides fragilis.

The study added to a working hypothesis in the field that microbes don’t just affect the permeability of the barrier around the brain but also influence the intestinal lining, which normally prevents certain bacteria from leaking out and others from getting in. When the intestinal barrier was compromised in his model, normally ‘‘beneficial’’ bacteria and the toxins they produce seeped into the bloodstream and raised the possibility they could slip past the blood-brain barrier. As one of his colleagues, Michael Fischbach, a microbiologist at the University of California, San Francisco, said: ‘‘The scientific community has a way of remaining skeptical until every last arrow has been drawn, until the entire picture is colored in. Other scientists drew the pencil outlines, and Sarkis is filling in a lot of the color.’’

Mazmanian knew the results offered only a provisional explanation for why restrictive diets and antibacterial treatments seemed to help some children with autism: Altering the microbial composition might be changing the permeability of the intestine. ‘‘The larger concept is, and this is pure speculation: Is a disease like autism really a disease of the brain or maybe a disease of the gut or some other aspect of physiology?’’ Mazmanian said. For any disease in which such a link could be proved, he saw a future in drugs derived from these small molecules found inside microbes. (A company he co-founded, Symbiotix Biotherapies, is developing a complex sugar called PSA, which is associated with Bacteroides fragilis, into treatments for intestinal disease and multiple sclerosis.) In his view, the prescriptive solutions probably involve more than increasing our exposure to environmental microbes in soil, dogs or even fermented foods; he believed there were wholesale failures in the way we shared our microbes and inoculated children with these bacteria. So far, though, the only conclusion he could draw was that disorders once thought to be conditions of the brain might be symptoms of microbial disruptions, and it was the careful defining of these disruptions that promised to be helpful in the coming decades.

The list of potential treatments incubating in labs around the world is startling. Several international groups have found that psychobiotics had subtle yet perceptible effects in healthy volunteers in a battery of brain-scanning and psychological tests. Another team in Arizona recently finished an open trial on fecal transplants in children with autism. (Simultaneously, at least two offshore clinics, in Australia and England, began offering fecal microbiota treatments to treat neurological disorders, like multiple sclerosis.) Mazmanian, however, cautions that this research is still in its infancy. ‘‘We’ve reached the stage where there’s a lot of, you know, ‘The microbiome is the cure for everything,’ ’’ he said. ‘‘I have a vested interest if it does. But I’d be shocked if it did.’’

Lyte issues the same caveat. ‘‘People are obviously desperate for solutions,’’ Lyte said when I visited him in Abilene. (He has since moved to Iowa State’s College of Veterinary Medicine.) ‘‘My main fear is the hype is running ahead of the science.’’ He knew that parents emailing him for answers meant they had exhausted every option offered by modern medicine. ‘‘It’s the Wild West out there,’’ he said. ‘‘You can go online and buy any amount of probiotics for any number of conditions now, and my paper is one of those cited. I never said go out and take probiotics.’’ He added,

‘‘We really need a lot more research done before we actually have people trying therapies out.’’

If the idea of psychobiotics had now, in some ways, eclipsed him, it was nevertheless a curious kind of affirmation, even redemption: an old-school microbiologist thrust into the midst of one of the most promising aspects of neuroscience. At the moment, he had a rough map in his head and a freezer full of monkey fecals that might translate, somehow, into telling differences between gregarious or shy monkeys later in life. I asked him if what amounted to a personality transplant still sounded a bit far-fetched. He seemed no closer to unlocking exactly what brain functions could be traced to the same organ that produced feces. ‘‘If you transfer the microbiota from one animal to another, you can transfer the behavior,’’ Lyte said. ‘‘What we’re trying to understand are the mechanisms by which the microbiota can influence the brain and development. If you believe that, are you now out on the precipice? The answer is yes. Do I think it’s the future? I think it’s a long way away.’’

Peter Andrey Smith is a reporter living in Brooklyn. He frequently writes about the microbial world.
Reporting for this article was supported by the UC Berkeley-11th Hour Food and Farming Journalism Fellowship.

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References:

Link to Prior JCR Micorbiome post (on proteomics), July, 2014

JCR post on microbiomes, July, 2014

Microbiomes

Science is advancing on microbiomes in the gut. The key to food is fiber, and the key to best fiber is long fibers, like cellulose, uncooked or slightly sauteed (cooking shortens fiber length). The best vegetable, in the view of Jeff Leach, is a leek.

Eating Well Article on Microbiome

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How Good Gut Bacteria Could Transform Your Health
By Gretel H. Schueller, “The Wild World Within,” July/August 2014

Scientist Jeff Leach is studying gut microbes that have the potential to improve our weight, mood, allergies, heart and more.

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Fresh Leek Recipes

Barefoot and coated in fine desert dust, Jeff Leach hops around the fire, adjusting logs. Its roaring glow provides the only light as the sun sinks behind the Chisos Mountains and the desert air cools.
It’s dinnertime here in Terlingua, the tiny town in southwest Texas that Leach sometimes calls home. We’ve just finished piercing roughly chopped pieces of leek, onion, beef, green peppers and garlic onto metal skewers, and Leach works at balancing them over the fire. Juices sizzle and the roasting aroma makes my mouth water.
“Have you ever held a colon in your hands?” he asks. Whoa…
Talk of belly bacteria, stool samples, bowel movements or your colon isn’t supposed to be part of polite (or appetizing) dinner conversation. But eating with Leach requires new rules of etiquette. Actually, it requires rethinking a whole slew of “rules.”
Once you get talking to Leach and his research colleagues around the world, you quickly realize it’s not just about changing dinner-table etiquette—we may be changing how we talk about health entirely. It all centers on the trillions of bacteria living in our gut.
We are more microbe than human. We each carry an estimated four to ten times more bacterial cells than human cells. If you could mush all the bacteria together they’d be the size of a basketball and weigh about three pounds.
The invisible world of bacteria that live on and in us is called the microbiome; the gut microbiome is the term for the diverse collection living along our intestinal tract, where the bulk of our tiny partners make their home.

Research on the gut microbiome has exploded over the past few years. This bold new frontier may just provide the string theory of all human disease. “Name just about any ailment plaguing us and you’ll find some ­researchers discovering the microbial angle for a connection,” says Leach, whose latest book, Bloom: Reconnecting with Your Primal Gut in a Modern World, is due out this fall. Recent studies have implicated gut microbes in everything from autism and depression to cancer and diabetes to heart disease and obesity. “It’s a water­shed ­moment for human health,” says Leach.
He should know. Leach—with his frenetic energy, powerful charisma and uncanny ability to step back and connect diverse dots—is one of the most visible leaders of the gut-health movement. In 2012, Leach founded the Human Food Project, a global effort to study how diet affects the microbial world within us.

A major arm of that is the American Gut Project, thought to be the largest microbiome project in the world, co-led by Rob Knight, Ph.D., a professor at the University of Colorado’s BioFrontiers Institute and a Howard Hughes Medical Institute Early Career Scientist. The goal is to map the diversity of the ­human gut—and tease out patterns shaped by diet, age and lifestyle to understand the factors most important for a healthy gut microbiome.

So far, more than 7,000 people have signed up for the gut project. After completing a questionnaire and a 7-day food journal, and paying $99, participants send a fecal sample to be analyzed.

Some of the questions might seem odd: How many different plants do you eat in a week? Born by C-section? Own a pet? Used an anti­biotic in the past month?
But Leach explains that all of these things affect your microbiome. And what he and his colleagues are finding is that Americans generally have less-diverse gut microbiomes than other populations. No one knows what the perfect gut microbiome should look like—or if there even is one. But one thing is clear: diversity is key. And we’re losing it.

Building the Microbiome
Until the moment we are born, we are still 100 percent human. In other words, bacteria-free. Most of us get our first dose of microbes while traveling through the birth canal. The second big dose comes from breast milk. As babies grow, they pick up critters from dirt, pets, family members and friends. By age 3, the microbiome has pretty much set up camp.

But changing lifestyles are chipping away at that microbiome. Early studies indicate that children born by C-section—which reduces the microbes an infant is first exposed to—have a higher risk of celiac disease, obesity and type 1 diabetes. Add to that decreased breast-feeding and “our overzealous use of antibiotics,” says Leach, who compares what antibiotics do to the gut microbiome to clear-cutting a forest.

From birth to age 5, children receive more anti­biotics than during any other five-year period in their lives. One of Leach’s colleagues, New York University microbiologist Martin Blaser, M.D., believes antibiotics have “deranged” the micro­biome—even causing some species to go extinct—and that their overuse is why many health problems, including type 1 diabetes, obesity and allergies, are on the rise.

Numerous studies also show that scrubbing away our microbes may be weakening our bodies’ natural defenses—something Leach has experienced firsthand: 12 years ago, at age 2, his daughter was diagnosed with type 1 diabetes, an autoimmune disease.

“My daughter was born C-section—strike 1; breast-fed very short—strike 2; strike 3, she received antibiotics at a very young age; strike 4, she lived in an environment where we basically wet-wiped everything and bathed her twice a day.” Leach feels strongly that her disease is a by-product of our culture.

At the time, Leach, who has a Ph.D. in anthropology, was studying how ancient people acquired and cooked foods. “When my daughter was diagnosed, the only thing I could do was to try to under­stand why she was sick. I just started emailing microbiologists and asking questions.”

He learned that this autoimmune disease is an overreaction of the immune system. And the bulk of immune cells live in the gut. So into the gut he went—and stayed.

His new focus is actually not that much of a leap from anthropology. “If microbiome research is anything, it’s anthropology—about how people interact with their environment,” notes Leach.

Here in this remote desert town, Leach’s life is a sharp contrast to his sanitized suburban past.

e and his wife divorced and the children live with her most of the year.) When he’s not traveling for research, Leach spends time in an adobe ruin that he’s rehabbing.

The fire pit is his kitchen. He has an open-air shower and the toilet is in a doorless shed. Only one 7-by-12-foot room is closed to the elements; it includes a single cot, desk, laptop computers, leaning towers of research papers and…a few dozen poison-tipped arrows (we’ll get to those soon). Out here, Leach is reconnecting with his microbes because he knows how critical they are.

Most of our resident gut bacteria are real workhorses. Some aid in digestion and produce enzymes to break down foods. Others make vitamins, like B12 and K, and other vital compounds, such as the feel-good chemical serotonin. A few help keep the intestinal lining impenetrable. Some gut bacteria help regulate metabolism. And others boost immunity and fight pathogens.
Of course, not all bacteria are beneficial. Some amplify inflammation or cause life-threatening infections. But we carry them all naturally; they only create problems when the microbial balance becomes disturbed.

There are many ways our microbiome can get off-kilter and make us prone to infections or disease. For example, taking antibiotics shifts the balance of microbes in our gut. As a result, the infectious dose of Salmonella is a thousand times lower for someone who’s on antibiotics. Diet is another way we can tip the balance unfavorably.

Essential Fuel for Your Microbiome
“We should start thinking about diets from the perspective of what we should be feeding our gut microbes,” says Leach. “Nothing matters more.”
A seminal study published in Nature last year compared the gut microbiome of people eating an entirely animal-based diet (meats, cheeses and eggs) with one that was completely plant-based (grains, legumes, vegetables and fruits). Just one day on either diet was enough to dramatically shift the gut microbiome of participants. While researchers knew that diet could cause changes to the gut microbiome, this was the first study to show such a rapid effect in people.
Leach is doing similar, informal tests on himself. Since January 1 of this year, he’s been trying out different diets: fermented foods, vegan, raw food, Paleo and others. He’s following each one for 10 to 12 days, collecting daily stool samples. By “whacking his micro­biome around” (as he refers to it) he hopes to zero-in on the key foods that fuel the good and bad players of the gut.

His first trial was a high-fat (70 percent of calories), average-protein (25 percent) diet with little carbohydrate and near zero dietary fiber. This diet, he explains, starved his microbes of food. Proteobacteria, practically nonexistent before, increased.

“This group includes a lot of your bad guys—E. coli, Salmonella. They are associated with inflammation and may increase your risk of disease.” At the same time, numbers of actinobacteria, typically considered good guys and known to suppress proteobacteria, dropped.

He’s since done several variations of this diet—adjusting fat, carbs, protein and fiber. “It’s the fiber that’s the game changer,” Leach says. Adding 40 to 60 grams of fiber per day seems to shift his gut microbiome toward a diverse, more beneficial mix of microbes.

Here’s why: like all living things, bacteria need food to survive. They do that by fermenting—that’s the way these guys “eat”—dietary fiber. But gut bacteria are picky. Only certain types of fiber will do—and most of us don’t eat enough of the kind that bacteria need.

Fibers are like pearl necklaces of varying bead-length. Most fibers we eat are so short, they get chomped long before they make it to where bacteria are concentrated, the beginning of the large intestine, aka the colon.

Two fiber types long enough to survive the length of our GI tract are fructan and cellulose fibers—part of a group of foods known as prebiotics, foods that encourage the growth of good bacteria. Cellulose fibers are in the tough parts of veggies and fruit we tend to toss—like the stalks of broccoli and bottoms of asparagus—and the stringy bits of celery. Fructan fibers are found in many fruits and vegetables—from artichokes to onions.

But how you prepare these foods also matters. That’s because heat breaks down fibers. Consider the onion—a good source of fructan: the ­average chain length of fructan in an onion is 26. A little bit of cooking breaks the onion fibers down to 8 or 10 beads. The shorter the chain, the sweeter the food—which is why deliciously sweet caramelized onions retain little fructan fiber benefit.

Leach does a little show-and-tell at Terlingua’s only grocery, the Cottonwood General Store. “This is probably the healthiest thing in the store for your gut microbiome,” he says, holding a leek almost as long as his arm.

He points to the white part: “These store fructans. I’d say this probably does more good for you than a wheelbarrow full of yogurt.” Then, he points to the green top of the leek: “That’s the cellulose, which has a chain length of a couple thousand ‘beads.’”

A few onlookers stare at the leek in awe. Silence. “You could eat this whole leek and change your micro­biome in 48 hours,” Leach proclaims. In other words, if you eat this, the good guys will come.

In contrast, he pulls out a bag of baby carrots. “We think we’re doing well when we steam these for dinner,” Leach says. And for some purposes we are. But there’s not much here to feed your gut microbes.

When he’s not using himself to road-test various diets, Leach practices what he preaches, eating a (lightly sautéed) leek a day—“The whole thing,” he emphasizes, “from muddy roots to fibrous green tops.” In fact, he convinced this tiny grocery store in the middle of a desert to carry leeks.

Gut microbes feast away on those fibers in a fermentation frenzy. Some of fermentation’s most beneficial by-products are short-chain fatty acids that provide energy for intestinal cells, help repair the ­colon’s protective lining and increase the acidity of the colon. Most infection-causing bacteria—as well as other microscopic troublemakers like parasites—don’t do well in acidic environments.

A Gut Without Fiber
Starve your gut friends and the consequences can be toxic. Without fiber, the colon environment favors unsavory microbes. No fiber also means no more short-chain fatty acids, paving the way for less-desirable bacteria to flourish.
Over time, starving bacteria start eating us—specifically the lining of the ­colon. Normally, the intestinal lining is a selective barrier between our digestive tube and the rest of our body—harder to break into than a trendy club; good bacteria like bifidobacterium act as buff bouncers, making sure only the worthy get past. Over time, eating a low-fiber diet can weaken these defenses, allow­ing bits of dead bacteria to get into the bloodstream. “This is what causes low-grade inflammation,” Leach explains.

Chronic, low-grade inflammation can raise your risk for various chronic diseases—and it is a hallmark of metabolic syndrome, a collection of conditions that can include insulin resistance, elevated blood sugar and high blood pressure. Patrice Cani, Ph.D., a microbiologist at the Catholic University of Louvain in Belgium, is one of the leading researchers looking at the connection between inflammation and gut microbes.

His work has shown that a high-fat, low-fiber diet increases inflammation—that’s probably not a big surprise. The real shocker came when he and his colleagues fed gut-friendly plant fibers to mice on a high-fat diet: they were able to stop the whole inflammation cycle that fuels metabolic syndrome.

Our Original Microbiome
After our fireside dinner, Leach invites me into his adobe ruin to show me photos of the people he says will help us better understand the gut microbiome. They carry a gut microbe mix that’s close to the one our ancestors had, Leach believes. Photos of men hunting, straw huts and smiling children cover the walls. Leach is animated and starts pulling out souvenirs to show me: a drum, sandals made of old tires.

Then he brings out the arrows. Colorful feathers decorate the tail ends and the metal tips are sharp—and covered with dried blood. “Careful, don’t touch the tips. They’re poison.” The ­arrows belong to the Hadza of Tanzania, “the last true hunter-­gatherers in the world,” he says. “They live where humans evolved; it’s as close as we can get to the original microbiome.”

For the past year, Leach has been spending time with this dwindling tribe of roughly 300 people. The Hadza still hunt and gather the majority of their food, have limited access to antibiotics, are born naturally, breast-feed for two-plus years, drink untreated water and live outdoors 24-7—all things that encourage a diverse gut micro­biome.

While infant mortality—as in many developing countries—is high, Hadza adults are healthy and rarely suffer from “modern” diseases like heart disease, diabetes, allergies and cancer, according to Leach. Their diet shifts dramatically over the year: during the rainy season from February to April, as many as 80 percent of their calories come from honey; in contrast, late fall is characterized by meat bingeing. What remains constant is their average daily fiber intake: more than 100 grams. Most comes from the seeds and pulp of the fructan-rich baobab fruit and fibrous tubers.

It’s here with the Hadza that Leach sees the puzzle pieces fitting together—how the “dirty” world of the Hadza mirrors the robust world of their gut. “Once you’ve sat under a baobab tree for two weeks and watched how they drink water, build their houses, handle animals, travel—and the things they don’t do—there’s a lot of eureka moments.”

Fieldwork to help understand the bigger picture is what Leach does best. For the analysis and lab work, he has brought together a global “dream team,” as he calls them.
“Intellectually, [Leach’s] background and perspective are huge assets to the project,” says Justin Sonnenburg, Ph.D., a micro­biologist at Stanford University who collaborates with Leach and runs one of the labs involved in the Human Food Project. He receives some of the stool samples Leach collects from the tribe. Other samples arrive to other “dream team” members.

The first report on the Hadza micro­biome was recently published, showing the hunter-gatherers probably have the most diverse gut microbiome in the world, with hundreds more species than most other people. “It suggests that the microbiome is going through extinctions as food becomes more processed and less diverse,” notes Sonnenburg. “What does it mean if the world is heading down a path of reduced microbiome diversity?” He points to the fact that most Western diseases are spurred by inflammation.
This is why, taking a few lessons from the Hadza, we could do with a little re­wilding of our gut microbiome.

Right now, Leach is on a break from his diet experiment. So we sip tequila and eat some queso and chips at the local watering hole. (Not so gut-friendly, he acknowledges, but the occasional treat is OK.) I dunk a chip as Leach sketches a colon on my notepad.

Patrons at a nearby table nod with understanding—they’re familiar with Leach, who they sometimes affectionately call “Dr. Sh*t.” They appreciate his crusade as an environmentalist for the ecosystem within us.

There’s certainly more to be discovered in this diverse world tucked inside our ­bellies. But Leach believes we should already feel empowered. His basic message: increase and diversify your plant intake. The foods you pick “should be chewy, should get stuck in your teeth,” he says. “Eat the end of the asparagus, the stalk of the broccoli. Become a little more adventurous in the produce section. This is a part of your health you can control. You can shift your microbiome.”

Gretel H. Schueller has written for Scientific American, Discover and New Scientist. She is also a children’s book author.