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Published on Leave a comment on Eat More Fiber to Improve Your Gut Microbiome

Another article commenting that increasing the amount of dietary fiber eaten by people eating a typical Western diet (which is low in fiber) will improve their gut microbiome (community of microbes). Research is finding that the added dietary fiber is food (nutrition) for microbes in the gut, and eating additional fiber daily will help restore or increase bacterial diversity, which then should lead to health benefits. Note: Easy ways to increase dietary fiber are increasing intake of whole grains, legumes, nuts, seeds, fruits, and vegetables. Think of food writer Michael Pollan's advice: "Eat food. Not too much. Mostly plants."

Researchers feel that fiber intake needs to be increased to more than current dietary guidelines, and that beneficial effects to the microbiome starts to occur rapidly (within 2 weeks) of changing to a higher fiber diet. This post from January 21, 2016 discussed the Sonnenburg research on gut microbe depletion (from a low fiber diet), and this April 28, 2015 post discussed the O'Keefe research (changing the diet has big effect on colon cancer risk) - both studies are mentioned below. See the page Feeding Your Gut Microbes for more information. From Science Daily:

Can more fiber restore microbiome diversity?

Scientists are pushing to restore human health in Western countries by changing our diet to restore the microbial species lost over the evolution of Western diet. Researchers advocate for strategically increasing dietary fiber intake as one path forward in regaining microbial biodiversity.

Insufficient nutrients for our gut microbes have been linked to a loss of certain beneficial bacterial species in industrialized societies and are likely impacting our immunological and metabolic health, although more data is needed. For example, most Westerners consume half of the amount of dietary fiber recommended by dietary guidelines, which nutritionists refer to as the "fiber gap," which is a problem because dietary fiber is the primary source of nutrition (e.g., carbohydrates) accessible to gut bacteria in humans.

"The idea to boost fiber levels is not new," says Jens Walter of the University of Alberta, Canada. "However, depletion of the microbiome adds a new perspective to this low-fiber Western diet that we are currently eating." Earlier this year, Stanford University's Justin Sonnenburg found that mice fed a typical Western diet (high in fat and carbohydrates and low in fiber) transferred a lower diversity of beneficial microbial species to future generations. The re-introduction of the microbes' preferred fiber at that stage did not result in a return of some (good) species, indicating that extinctions had occurred in only a few generations.

Walter and co-author Edward Deehan, his PhD student, are concerned that a dramatic shift away from a diet similar to the one under which the human-microbiome symbiosis evolved is a key factor in the rise of non-communicable disorders like obesity. "There is a lot of epidemiological evidence that fiber is beneficial, and food products containing dietary fiber have FDA-approved health claims for both colon cancer and coronary heart disease. There is also quite a bit of clinical evidence (although it is less consistent)," Walter says. "The most pressing issue at the moment that neither consumption of fiber in society nor the doses used in clinical research are high enough."

People living in non-industrialized societies have an average intake of fiber that is much higher than the low norms of Western societies. The authors note the recent work from the Stephen J.D. O'Keefe lab in Nature Communications in which modern African-Americans were given a traditional South-African diet that contained 55 grams of daily dietary fiber and had improved markers for colon cancer within two weeks.

Published on Leave a comment on Our Gut Microbes Need Dietary Diversity

A thought-provoking article by Heiman and Greenway was just published in the journal Molecular Metabolism making the case that changes in farming practices over the last 50 years have resulted in decreased agricultural diversity which, in turn, has resulted in decreased dietary diversity, and that the reduction in dietary diversity has changed and decreased the richness of the human gut microbiota (microbes living in the gut). And meanwhile, during the past 50 years, the rates of obesity, type 2 diabetes, and inflammatory bowel diseases sharply increased - and in each of these conditions there is a reduction of the gut microbial diversity. Similar views have also been stated by others in the field of microbiology.

The thinking is that the more diverse the diet, the more diverse the gut microbiome (and healthier), and the more it can adapt to disturbances. Heiman and Greenway state: "Unfortunately, dietary diversity has been lost during the past 50 years because of economic pressures for greater food production to support a growing world population.... Of the 250,000 to 300,000 known edible plant species, humans use only 150 to 200...Today, 75 percent of the world's food is generated from only 12 plants and five animal species."

Also, agricultural practices of using antibiotics as growth promoters for poultry, swine, and cattle further harm the human gut microbiome when the meat is ingested by humans, and pesticide residues on crops ingested by humans may have gut microbiome effects. Even emulsifiers, used in processed foods, reduce microbial richness. Every time a person goes on a certain diet (vegan, Paleo, etc) or makes dietary choices in which some foods are eliminated, it makes it easier for some microbial species, and gives them a competitive advantage over other gut microbes. From Science Daily:

Reduction in dietary diversity impacts richness of human gut microbiota

Changes in farming practices over the last 50 years have resulted in decreased agro-diversity which, in turn, has resulted in decreased dietary diversity. The significant impact of this change in dietary richness on human health is an emerging topic for discussion

Heiman and Greenway describe how the reduction in dietary diversity has changed the richness of human gut microbiota, the community of microorganisms living in the gut. The researchers point out that healthy individuals have diverse gut microbiota and many of the common pathologies of the 21st century, including type 2 diabetes, obesity and inflammatory bowel disease, are associated with reduced microbiotic richness.

Gut microbiota function as an endocrine organ, metabolizing specific nutrients from the diet and producing specific substances that act as metabolic signals in the host. It follows then that highly specialized diets will change the landscape of the gut microbiome over time. In fact, it takes only a few days of changing diet to alter the microbiotic makeup of the human gut. And if the dietary change involves elimination of one or more macronutrients (think Atkins or Paleo or vegan), humans are essentially selecting for some microbiotic species over others.

The importance of microbiota diversity cannot be overstated. They produce an abundance of important molecules for the host and with increased variation comes increased adaptability and an increased range of physiological responses. "The greater the repertoire of signals, the more likely is the ability to maintain homeostasis when dietary intake is perturbed," explain Heiman and Greenway. "Furthermore, because each particular macronutrient has the potential to be metabolized by microbiota into unique metabolic signals, the greater the variety in signals, the greater the variety of responses possible."

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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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The numbers are amazing. Researchers found all these microbes because of state of the art genetic analysis such as 16S rRNA gene sequencing (because most microbes can not be "cultured"). From Science Daily:

Cataloguing 10 million human gut microbial genes: Unparalleled accomplishment

Over the past several years, research on bacteria in the digestive tract (gut microbiome) has confirmed the major role they play in our health. An international consortium has developed the most complete database of microbial genes ever created. The catalogue features nearly ten million genes and will constitute a reference for all research on gut bacteria.

Research on the gut microbiome (all of the bacteria in the digestive tract) has multiplied over the past several years, helped in great part by new sequencing technologies. The gut microbiome, which scientists have labelled a "new organ" that is composed of tens of trillions of bacteria -- ten times as many as the number of cells in the human body -- is directly linked to the immune system and brain. It is a major player in chronic illnesses such as obesity and Type 2 diabetes. However, research in the field depends on access to reference gene databases (or catalogues), which is particularly important when identifying the functions of microbial genes. Few and far between, existing catalogues were created using samples from a limited number of people and geographical origins.

Most of the genes (around six million) are shared by just 1% of the population, making them quite rare. While there is substantial data today regarding the most common genes, future research will focus on determining the importance and role of these rare genes.

Thanks to this catalogue, the most clinically significant genes can be described, most notably those related to illnesses such as Type 2 diabetes, cirrhosis of the liver, cardiovascular diseases and some cancers. It will also provide a more complete picture of imbalances in the gut microbiome (dysbiosis), particularly those caused by medication.

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An amazing and unforgettable story of a man researching the gut microbes that are increasingly lost in developed Westernized populations. And do go read the original story (see link).From Popular Science:

Scientist Gives Himself Fecal Transplant To Try A Hunter-Gatherer's Microbiome

Why a field researcher from America has exposed his colon to the gut microbiome of a tribesman from Tanzania.

It's not often we encounter a story that begins with a line like this: “AS THE SUN set over Lake Eyasi in Tanzania, nearly thirty minutes had passed since I had inserted a turkey baster into my bum and injected the feces of a Hadza man – a member of one of the last remaining hunter-gatherer tribes in the world – into the nether regions of my distal colon.”

The guy behind this essay, Jeff Leach, is part of a multi-national scientific research team that by his account has been living with the Hadza, hunter-gatherers in Tanzania, for over a year. They have collected hundreds of samples from humans, animals, and the environment in order to observe how the microbial communities in and around the Hadza change with the dramatic seasonal weather shifts in East Africa: six months of near-steady rain followed by six dry months.

The question driving the research is “what a normal or healthy microbiome might have looked like before the niceties and medications of late whacked the crap out of our gut bugs in the so-called modern world,” Leach writes.

The Hadza are contemporary people, Leach writes, not an undiscovered stone-age civilization. But they're excellent subjects for this research because they still live on plant and animal foods that humans have hunted and gathered for millennia, and their use of western medications is extremely limited.

The health impacts of what lives (or doesn't) in our guts are getting increased attention in Western dietary and medical circles -- and eating foods containing "probiotics" just scratches the surface. Recent research suggests that use of antibiotics may be fundamentally altering our gut biomes for the worse, increasing rates of allergies, asthma and weight gain.

As for fecal transplants, they're no longer career killers in polite medical conversation. Swapping poop from healthy to sick persons is now an up-and-up treatment for curing chronic gastrointestinal disease. The launch of the OpenBiome fecal transplant bank in the U.S. earlier this year seems to signal that the technique is going mainstream.

As for Jeff Leach, he describes his primary scientific motivation for self-administering a fecal transplant as testing the hypothesis "of microbial extinction, something I believe we all suffer from in the western world and may be at the root of what’s making us sick." The biggest change Leach and his girlfriend have noticed since the transplant is that he's passing a lot less gas. 

Read the rest of his very readable, informative and down-to-earth essay: (Re)Becoming Human: what happened the day I replaced 99% of the genes in my body with that [sic] of a hunter-gatherer.

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Amazing possibilities, but more studies needed. The key finding: A diversity of the bacterial community in the gut is good, and perhaps can be altered through diet, and so perhaps alter the future risk of developing breast cancer.From Science Daily:

Diverse gut bacteria associated with favorable ratio of estrogen metabolites

Postmenopausal women with diverse gut bacteria exhibit a more favorable ratio of estrogen metabolites, which is associated with reduced risk for breast cancer, compared to women with less microbial variation, according to a new study.

Since the 1970s, it has been known that in addition to supporting digestion, the intestinal bacteria that make up the gut microbiome influence how women's bodies process estrogen, the primary female sex hormone. The colonies of bacteria determine whether estrogen and the fragments left behind after the hormone is processed continue circulating through the body or are expelled through urine and feces. Previous studies have shown that levels of estrogen and estrogen metabolites circulating in the body are associated with risk of developing postmenopausal breast cancer.

"In women who had more diverse communities of gut bacteria, higher levels of estrogen fragments were left after the body metabolized the hormone, compared to women with less diverse intestinal bacteria," said one of the study's authors, James Goedert, MD, of the National Institutes of Health's National Cancer Institute (NCI) in Bethesda, MD. "This pattern suggests that these women may have a lower risk of developing breast cancer."

As part of the cross-sectional study, researchers analyzed fecal and urine samples from 60 postmenopausal women enrolled in Kaiser Permanente Colorado. .

"Our findings suggest a relationship between the diversity of the bacterial community in the gut, which theoretically can be altered with changes in diet or some medications, and future risk of developing breast cancer," Goedert said. 

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Future microbiome research and therapy will have to take into account that diet affects the gut microbes of men and women differently. From Science Daily:

Diet affects males' and females' gut microbes differently

The microbes living in the guts of males and females react differently to diet, even when the diets are identical, according to a new study. These results suggest that therapies designed to improve human health and treat diseases through nutrition might need to be tailored for each sex.

The researchers studied the gut microbes in two species of fish and in mice, and also conducted an in-depth analysis of data that other researchers collected on humans. They found that in fish and humans diet affected the microbiota of males and females differently. In some cases, different species of microbes would dominate, while in others, the diversity of bacteria would be higher in one sex than the other.

These results suggest that any therapies designed to improve human health through diet should take into account whether the patient is male or female.

Genetics and diet can affect the variety and number of these microbes in the human gut, which can in turn have a profound influence on human health. Obesity, diabetes, and inflammatory bowel disease have all been linked to low diversity of bacteria in the human gut.

Why men and women would react differently to changes in diet is unclear, but there are a couple of possibilities. The hormones associated with each sex could potentially influence gut microbes, favoring one strain over another. Also, the sexes often differ in how their immune systems function, which could affect which microbes live and die in the microbiome.

One notable exception in Bolnick's results was in the mice. Although there was a tiny difference between male and female mice, for the most part the microbiota of each sex reacted to diet in the same manner. Because most dietary studies are conducted on mice, this result could have a huge effect on such research, and it raises questions about how well studies of gut microbes in lab mice can be generalized to other species, particularly humans.

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This research illustrates how little we currently know about gut bacteria.But it did show the importance of diet. From Science Daily:

Monitoring rise and fall of the microbiome

Trillions of bacteria live in each person's digestive tract. Scientists believe that some of these bacteria help digest food and stave off harmful infections, but their role in human health is not well understood.

To help shed light on the role of these bacteria, a team of researchers led by MIT associate professor Eric Alm recently tracked fluctuations in the bacterial populations of two research subjects over a full year. The findings, described in the July 25 issue of the journal Genome Biology, suggest that while these populations are fairly stable, they undergo daily fluctuations in response to changes in diet and other factors...."To a large extent, the main factor we found that explained a lot of that variance was the diet."

There are a few thousand strains of bacteria that can inhabit the human gut, but only a few hundred of those are found in any given individual, Alm says. For one year, the two subjects in the study collected daily stool samples so bacterial populations could be measured. They also used an iPhone app to track lifestyle factors such as diet, sleep, mood, and exercise, generating a huge amount of data.

Analysis of this data revealed that dietary changes could produce daily variations in the populations of different strains of bacteria. For example, an increase in fiber correlated with a boost in the populations of Bifidobacteria, Roseburia, and Eubacterium rectale. Four strains -- including Faecalibacterium prausnitzii, which has been implicated in protecting against inflammatory bowel disease -- were correlated with eating citrus.

During the study, each of the two subjects experienced an event that dramatically altered the gut microbiome. Subject B experienced food poisoning caused by Salmonella, and Subject A traveled to a developing nation, where he experienced diarrheal illness for two weeks.

During Subject B's infection, Salmonella leapt from 10 percent of the gut microbiome to nearly 30 percent. At the same time, populations of bacteria from the phylum Firmicutes, believed to be beneficial to human health, nearly disappeared. After the subject recovered, Firmicutes rebounded to about 40 percent of the total microbiome, but most of the strains were different from those originally present.

Subject A also exhibited severe disruptions to his microbiome during his trip, but once he returned to the United States, it returned to normal. Unlike Subject B's recovery from food poisoning, Subject A's populations returned to their original composition.

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If you missed these recent articles about weight and gut bacteria, please go read them now. Amazing stuff. From the December 9, 2013 Washington Post:

The microbes in your gut may be making you fat or keeping you thin

 ...a growing body of evidence suggesting that naturally occurring bacteria and other microbes in the body, and possibly even viruses, can influence weight in ways that scientists are only just beginning to understand. Numerous studies are underway looking at the role of intestinal organisms in obesity, with a focus on how they extract energy from food and how this affects weight gain or loss.

From September 5, 2013 Science News: Gut infections keep mice lean

Skinniness could be contagious. Gut bacteria from thin people can invade the intestines of mice carrying microbes from obese people. And these invaders can keep mice from getting tubby, researchers report in the Sept. 6 Science.

But the benefits come with a catch. The invading microbes drop in and get to work only when mice eat healthy food. Even fat-blocking bacteria can’t fight a bad diet, suggests study leader Jeffrey Gordon, a microbiologist at Washington University in St. Louis. 

Fat and thin people have different microbes teeming in their intestines, for example. And normal-weight mice given microbes from obese mice pack on extra fat, says coauthor Vanessa Ridaura, also of Washington University.

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Some recent studies have explored the link between bacteria in the gut and colorectal cancer. The beneficial Prevotellaceae bacteria (mentioned in the Nov. 5 study below) have been discussed elsewhere as liking whole grain foods. So go feed your gut with some nice whole grain bread or cereal. And some fruits and veggies while you're at it. As mom used to say: "You are what you eat."

A study published December 6, 2013 found that decreased diversity of the gut microbiome and the presence of certain types of bacteria were associated with colorectal cancer in humans: Decreased Diversity of Bacteria Microbiome in Gut Associated Colorectal Cancer

From the November 5, 2013 Science Daily: Microbes in the Gut Help Determine Risk of Tumors

Transferring the gut microbes from a mouse with colon tumors to germ-free mice makes those mice prone to getting tumors as well, according to the results of a study published in mBio®, the online open-access journal of the American Society for Microbiology. The work has implications for human health because it indicates the risk of colorectal cancer may well have a microbial component.

Scientists have known for years that inflammation plays a role in the development of colorectal cancer, but this new information indicates that interactions between inflammation and subsequent changes in the gut microbiota create the conditions that result in colon tumors.

Known risk factors for developing colorectal cancer include consuming a diet rich in red meat, alcohol consumption, and chronic inflammation in the gastrointestinal tract (patients with inflammatory bowel diseases, such as ulcerative colitis, are at a greater risk of developing colorectal cancer, for instance).

The results were stark: mice given the microbiota of the tumor-bearing mice had more than two times as many colon tumors as the mice given a healthy microbiota. What's more, normal mice that were given antibiotics before and after inoculation had significantly fewer tumors than the mice that got no antibiotics, and tumors that were present in these antibiotic-treated mice were significantly smaller than tumors in untreated mice. This suggests that specific populations of microorganisms were essential for the formation of tumors...

Looking at the microorganisms, they found that tumor-bearing mice harbored greater numbers of bacteria within the Bacteroides, Odoribacter, and Akkermansia genera, and decreased numbers of bacteria affiliated with members of the Prevotellaceae and Porphyromonadaceae families. Three weeks after they were inoculated with the communities from the tumor-bearing mice, the germ-free mice had a gut microbiome that was very similar to the tumor-bearing mice, and they had a greater abundance of the same bacterial groups associated with tumor-formation.