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Low-Fiber Diets Cause Waves of Extinction in the Gut

Over generations, mice deprived of fiber permanently lost some species of gut microbes. What does this mean for human health?
Francisco Bonilla / Reuters

In the decades after World War II, a one-eyed Irish missionary-surgeon named Denis Burkitt moved to Uganda, where he noted that the villagers there ate far more fiber than Westerners did. This didn’t just bulk up their stools, Burkitt reasoned; it also explained their low rates of heart disease, colon cancer, and other chronic illnesses. “America is a constipated nation,” he once said. “If you pass small stools, you have big hospitals.”

“Burkitt really nailed it,” says Justin Sonnenburg, a microbiologist at Stanford University. Sure, some of the man’s claims were far-fetched, but he was right about the value of fiber and the consequences of avoiding it. And Sonnenburg thinks he knows why: Fiber doesn't just feed us—it also feeds the trillions of microbes in our guts.

Fiber is a broad term that includes many kinds of plant carbohydrates that we cannot digest. Our microbes can, though, and they break fiber into chemicals that nourish our cells and reduce inflammation. But no single microbe can tackle every kind of fiber. They specialize, just as every antelope in the African savannah munches on its own favored type of grass or shoot. This means that a fiber-rich diet can nourish a wide variety of gut microbes and, conversely, that a low-fiber diet can only sustain a narrower community.

Sonnenburg, his wife Erica, and the graduate student Samuel Smits confirmed this idea in a recent experiment. The researchers started with mice that had been raised in sterile bubbles and then loaded with identical collections of gut microbes. They then fed these mice a high-fiber diet, before randomly switching half of them to low-fiber chow for seven weeks.

Predictably, the fall in fiber caused upheavals in the rodents’ guts. In the low-fiber group, the numbers of 60 percent of the local microbe species fell dramatically, and some remained low even after the mice returned to high-fiber meals. Those seven low-fiber weeks left lingering scars on the animals’ microbiomes.

These scars can cascade through generations. Mice regularly eat each others' poop, and pups often pick up their parents’ microbes in this way. Indeed, when Sonnenburg and Smits bred the mice from their first experiment, they saw that low-fiber parents gave birth to pups with narrower microbiomes, which lacked species present in the progeny of high-fiber parents. And if these bacteria-impoverished pups also ate low-fiber food, they lost even more microbes, especially those from the fiber-busting Bacteroidales group. As four generations ticked by, the rodents’ guts became progressively less diverse, as more and more species blinked out.

It also became increasingly hard to reverse these changes. If the fourth-generation mice switched to high-fiber meals, some of the missing microbes rebounded, but most did not. In other words, these species weren't just lying in wait in small numbers, waiting for the chance to bloom again; they had genuinely vanished. The only way of restoring these missing microbes was through a fecal transplant—loading them with the entire gut microbiomes of rodents that had always eaten a high-fiber diet.

These changes parallel those that have taken place over the course of human history. Many studies have now shown that the gut microbiomes of Western city-dwellers are less diverse than those of rural villagers and hunter-gatherers, who eat more plants and thus more fiber. The Stanford researchers’ experiment hints (but doesn't confirm) that this low diversity could be a lasting legacy of industrialization, in which successive generations of low-fiber meals have led to the loss of old bacterial companions. “The data we present also hint that further deterioration of the Western microbiota is possible,” the team writes.

“Given the infancy of the microbiome field, I think it is difficult to determine what specific impacts the loss of microbiota diversity has on the host,” says Kelly Swanson, a nutritional-science professor at the University of Illinois at Urbana-Champaign. “But I think this paper provides even more evidence for including an adequate amount of dietary fiber in the diet.” For context, dietary guidelines recommend that women and men should respectively eat around 25 and 38 grams of fiber per day, but American adults eat just 15 daily grams on average.

This could be problematic for two reasons. First, without fiber, starving microbes often turn their attention to similar molecules, including those in the mucus layer that covers the gut. If they erode this layer sufficiently, they might be able to enter the lining of the gut itself, triggering immune reactions that lead to chronic inflammation.

Second, there’s evidence that a diverse microbiome can better resist invasive species like Salmonella or Clostridium difficile, while low diversity is a common feature of obesity, inflammatory bowel disease, and other conditions.

Still, no one has shown that a less-diverse microbiome is the cause of the health problems associated with low fiber intake.This means that it’s premature to talk about supplementing our microbiomes with those from communities that eat more fiber. Sonnenburg’s team writes, “It is possible that rewilding the modern microbiota with extinct species may be necessary to restore evolutionarily important functionality to our gut.” Sure, but first, they’d need to show if the microbial losses in their experiments matter, and to what degree.

After all, the diversity of the human microbiome has been falling long before industrialization. Even the rich gut communities of hunter-gatherers are a pale reflection of those of chimps and gorillas, whose diets are even richer in plants. The point is that animals tend to end up with the microbiomes they need; as our needs and habits change, so does our pool of partners.

Sonnenburg's concern is that these changes play out over millennia, and hosts and microbes have time to acclimate to their new relationships. By contrast, our modern diets and lifestyles are changing our microbiomes very quickly, leaving us with communities that we haven't adjusted to. “Our human genome is constantly trying to keep up with this moving target of a microbial community,” he says. “If there are times when changes are exceptionally rapid, it might be problematic for host health.” http://www.theatlantic.com/science/archive/2016/01/fiber-gut-bacteria-microbiome/423903/


A study by Stanford University School of Medicine investigators raises concerns that the lower-fiber diets typical in industrialized societies may produce internal deficiencies that get passed along to future generations.

The study, conducted in mice, indicates that low-fiber diets not only deplete the complex microbial ecosystems residing in every mammalian gut, but can cause an irreversible loss of diversity within those ecosystems in as few as three or four generations.

Once an entire population has experienced the extinction of key bacterial species, simply "eating right" may no longer be enough to restore these lost species to the guts of individuals in that population, the study suggests. Those of us who live in advanced industrial societies may already be heading down that path.

The proliferation of nearly fiber-free, processed convenience foods since the mid-20th century has resulted in average per capita fiber consumption in industrialized societies of about 15 grams per day. That's as little as one-tenth of the intake among the world's dwindling hunter-gatherer and rural agrarian populations, whose living conditions and dietary intake presumably most closely resemble those of our common human ancestors, said Justin Sonnenburg, PhD, associate professor of microbiology and immunology and senior author of the study, to be published Jan. 13 in Nature.

Suboptimal diets

Virtually all health experts agree that low-fiber diets are suboptimal. Probably the chief reason for this is that fiber, which can't be digested by human enzymes, is the main food source for the commensal bacteria that colonize our colons, Sonnenburg said.

Thousands of distinct bacterial species inhabit every healthy individual's large intestine. "We would have difficulty living without them," he said. "They fend off pathogens, train our immune systems and even guide the development of our tissues." While we pick up these microscopic passengers in the course of routine exposures throughout our lifetimes, one of the most significant sources of our intestinal bacterial populations is our immediate family, especially our mothers during childbirth and infancy.

Surveys of humans' gut-dwelling microbes have shown that the diversity of bacterial species inhabiting the intestines of individual members of hunter-gatherer and rural agrarian populations greatly exceeds that of individuals living in modern industrialized societies, Sonnenburg said. In fact, these studies indicate the complete absence, throughout industrialized populations, of numerous bacterial species that are shared among many of the hunter-gatherer and rural agrarian populations surveyed, despite those groups' being dispersed across vast geographic expanses ranging from Africa to South America to Papua New Guinea.

High- versus low-fiber diet

"Numerous factors including widespread antibiotic use, more-frequent cesarean sections and less-frequent breastfeeding have been proposed for why we see this depletion in industrialized populations," said the study's lead author, Erica Sonnenburg, PhD, a senior research scientist at Stanford (she and Justin Sonnenburg are married). "We asked ourselves whether the huge difference in dietary fiber intake between traditional and modern populations could, alone, account for it."

The Stanford researchers employed young laboratory mice that had been specially bred and raised in aseptic environments so that, unlike ordinary mice (and ordinary humans), their intestines were devoid of any microbial inhabitants. After populating the mice's guts with microbes from a human donor, the scientists divided them into two groups. One group was fed a diet rich in plant-derived fiber. The other group's diet, equivalent to the first with respect to protein, fat and calories, was practically devoid of fiber content.

During the experimentation that followed, the researchers analyzed fecal samples from the animals. The two groups' gut-bacteria profiles were initially indistinguishable but soon diverged. "Within a couple of weeks, we saw a massive change," said Justin Sonnenburg. "The low-fiber-intake mice harbored fewer bacterial species in their gut." More than half of these bacterial species' numbers had dwindled by over 75 percent, and many species seemed to have disappeared altogether.

After seven weeks, the mice that had consumed a low-fiber diet were switched back to a high-fiber diet for four weeks. The mice's gut-bacteria profiles partly recovered -- probably due to an uptick in abundance of some bacteria whose ranks had declined to undetectable levels during the low-fiber-intake period. Still, this restoration was only partial: One-third of the original species never fully recovered despite their return to a high-fiber diet.

No such changes were seen in the control mice consistently fed a high-fiber diet.

Generational effects

The real surprise came after mice had been bred and maintained on low-fiber diets for a few generations. In their experimental confines, these mice were exposed to microbes only through contact with their parents. Each successive generation's gut-bacterial ecosystem declined in diversity. By generation four, the depletion had reached a point where nearly three-quarters of the bacterial species resident in their great-grandparents' guts appeared absent in their own. Even after these mice were put back on a high-fiber diet, more than two-thirds of the bacterial species identified in the guts of their first-generation ancestors proved irretrievable, indicating extinction of those species by the fourth generation of fiber deprivation.

On the other hand, a somewhat more aggressive measure -- fecal transplantation -- did result in these lost species' retrieval, the study found. Introducing fecal contents of fourth-generation high-fiber-diet mice into the intestines of fourth-generation low-fiber mice, together with putting them on the high-fiber diet for two weeks, fully restored their bacterial profiles. Within 10 days of the procedure, the composition and diversity of the bacteria in the intestines of this group were indistinguishable from those of control mice.

These findings hold major implications for humans, said Erica Sonnenburg. "There are very few ecosystems where low species diversity is a good thing. There's no reason to think our gut is any exception," she said.

Possible fixes

"The extremely low-fiber intake in industrialized countries has occurred relatively recently," noted Justin Sonnenburg. "Is it possible that over the next few generations we'll lose even more species in our gut? And what will the ramifications be for our health?"

Simple tweaks in our cultural practices -- for example, not washing our hands after gardening or petting our dogs -- could be a step in the right direction, and steering away from overuse of antibiotics certainly is, he said. More extreme measures, such as mass fecal transplants, would require large-scale testing to make sure they are both necessary and safe.

Story Source:

The above post is reprinted from materials provided by Stanford University Medical Center. The original item was written by Bruce Goldman. Note: Materials may be edited for content and length.

Journal Reference:

Erica D. Sonnenburg, Samuel A. Smits, Mikhail Tikhonov, Steven K. Higginbottom, Ned S. Wingreen, Justin L. Sonnenburg. Diet-induced extinctions in the gut microbiota compound over generations. Nature, 2016; 529 (7585): 212 DOI: 10.1038/nature16504

Stanford University Medical Center. "Low-fiber diet may cause irreversible depletion of gut bacteria over generations." ScienceDaily. ScienceDaily, 13 January 2016. <www.sciencedaily.com/releases/2016/01/160113160657.htm>. http://www.sciencedaily.com/releases/2016/01/160113160657.htm
 
Onzin! Vezels spelen slechts een zeer marginale rol in de gezondheid van de darmen. Dit wordt voortdurend buiten proportie opgeblazen.

Mike
 
Health Hazards of Low-Fiber Diets Linked to Its Influence on Microbiome
January 25, 2016 Low-fiber diets can cause as much as 60 percent of microbe species in your gut to go extinct, and this altered gut flora gets passed on to future generations
As a general rule, people who eat a more plant-based diet and fermented foods tend to have a more diverse gut microbiome than those who skimp on fresh veggies and fruits and eat more processed foods
Some of the factors that affect your gut microbiome include diet, exercise, vaginal birth versus C-section, breast feeding, use of antibiotics and certain heartburn medication http://articles.mercola.com/sites/articles/archive/2016/01/25/low-fiber-diet-health-hazards.aspx?e_cid=20160125Z1_DNL_art_1&utm_source=dnl&utm_medium=email&utm_content=art1&utm_campaign=20160125Z1&et_cid=DM95963&et_rid=1329601701


 
IP6 is inositol hexafosfaat: IP6 staat bekend als ontgiftingsstof en antioxidant.
Wordt gebruikt bij ontgifting van zware metalen, bij kanker en bij het voorkomen van nierstenen.

Het wordt gevonden in onoplosbare vezels. In volkoren granen, peulvruchten, noten en zaden en zemelen.

Anticancer Res. 1998 Nov-Dec;18(6A):4083-90.
IP6 in treatment of liver cancer. I. IP6 inhibits growth and reverses transformed phenotype in HepG2 human liver cancer cell line.
Vucenik I1, Tantivejkul K, Zhang ZS, Cole KE, Saied I, Shamsuddin AM.

Hepatocellular carcinoma (HCC) is a common tumor world-wide with extremely poor prognosis. Recent studies have shown that inositol hexaphosphate (IP6), a naturally occurring carbohydrate, has novel anti-cancer function in various in vitro and in vivo models. The aim of this study was to assess whether IP6 could inhibit the growth of human hepatocellular carcinoma. We treated HepG2, a human liver cancer cell line in vitro with IP6 and evaluated its effect on growth and differentiation. IP6 treatment of HepG2 cells caused a dose-dependent growth inhibition. Compared to other cancer cell lines, HepG2 cells were quite sensitive to IP6, IC50 (50% inhibition of cell growth) of IP6 being < 1.0 mM (0.338 mM). Treatment with IP6 decreased the ability of HepG2 cells to form colonies, as assessed in the plating efficiency assay. Morphological changes induced by IP6 were consistent with differentiation of HepG2 cells. Exposure of HepG2 cells to IP6 drastically decreased the rate of production of alpha-fetoprotein (AFP), a tumor marker of HCC, indicating also that IP6 treatment leads to differentiation of malignant liver cells. Further, IP6 treatment caused a decreased expression of mutant p53 protein in HepG2 cells, with no significant change in the expression of wild-type p53. The expression of p21WAF1 protein was increased by 1.5 fold, as determined by immunocytochemical staining and ELISA assay. These data demonstrate that IP6 inhibits the growth, and induces differentiation, and a less aggressive phenotype of HepG2 cells, suggesting a role of IP6 in the treatment of HCC. http://www.ncbi.nlm.nih.gov/pubmed/9891449
 

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