Don’t poo-poo the poop

In the late 70’s, the medical faculty at UCSF was abuzz with excitement: Denis Burkitt, the astute physician who discovered a new kind of childhood cancer, called after him Burkitt’s lymphoma, while he was a medical missionary in Kampala, Uganda, was giving grand rounds, a school-wide lecture by medical luminaries. His opening slide proclaimed in bold letters:

America is a constipated nation…If you pass small stools, you have to have large hospitals.

And audible gasp swept through the hall. He quickly followed with:

How many of you men have any idea of the size of your wives’ stools?” 

Uproarious laughter. But the point was made: As Western physicians, we are absorbed with technology and esoteric science but are ignorant of the very basic things about diseases that afflict our patients.

In Africa, treating people who live largely off the land on vegetables they grow, I hardly ever saw cases of many of the most common diseases in the United States and England — including coronary heart disease, adult-onset diabetes, varicose veins, obesity, diverticulitis, appendicitis, gallstones, dental cavities, hemorrhoids, hiatal hernias, and constipation. Western diets are so low on bulk and so dense in calories, that our intestines just don’t pass enough volume to remain healthy.”

As he was saying it, photos of voluminous African poops—he took on his walk through the bush—were flashing in quick succession, culminating with…a slide of an English schoolboy’s meager poop.

When the laughter died down, you could hear a pin drop, as the audience of physicians, surgeons, and scientists was following, with rapt attention, the substance of the presentation. And finally, true to its UCSF reputation of rigor, the questioning from the audience was respectful, even adulatory at times, but highly skeptical. Yes, the volume and quality of the environmental/ecological data were impressive. But the conclusions were simplistic and overreaching. The critique boiled down to “great epidemiology, but what’s the mechanism, and what is the physiological and molecular evidence for it?” None was forthcoming.

A few years later, evidence came pouring in, and from unexpected corners.

 

The intestinal microbiome

First, what is fiber? Dietary fiber consists of complex carbohydrates that are contained in plants that the body is unable to digest. Dietary fiber is classified as either soluble fiber or insoluble fiber, depending on its solubility in water and other factors. Soluble fiber binds bile and delays the time taken for digested food to move through the intestines. Insoluble fiber speeds up the process of food traveling through the intestines.

The fact that we cannot digest fiber explains the increased bulk of stool, the decreased transit time in the colon, the binding of bile acids (presumed to be carcinogenic), the slowing of absorption of sugars and consequently reducing the insulin peak caused by high sugar concentration entering the circulation over a short period time, with its hypoglycemia-hyperglycemia roller coaster effect.

Gut flora bacteria Source: blog.paleohackers.com
Gut flora bacteria | blog.paleohackers.com

All salutary effects to be sure, but they couldn’t fully explain the varied health benefits of fiber. The crucial element in fully understanding fiber’s effects materialized with the advent of inexpensive and rapid analysis of the gene sequences. It enabled us to confirm the fact that every person’s gut is home to a unique cocktail of trillions of bacteria and other minute bugs that help to break down food and fight off invading pathogens. It also allowed the identification of these bacteria. Then came the really interesting payoff: We could start making direct relationship between the makeup of gut flora and health. Jeffrey Gordon and his colleagues at the Washington University School of Medicine in St. Louis strained the feces of 12 willing obese volunteers, used genetic sequencing to identify the different species of bacteria in there, and compared them with five lean volunteers. They found that most of the gut bacteria fall into two groups, called Firmicutes or Bacteroidetes. But the obese volunteers in their study had more than 20% more Firmicutes and nearly 90% less Bacteroidetes than the lean ones.

The obese volunteers then spent one year on a low-fat or low-carbohydrate diet, and lost as much as 25% of their body weight. At the same time, the proportion of Firmicutes in their colon dropped and that of the Bacteroidetes rose, although these levels never reached those of the group who were slim to start with. This suggests that our bodies somehow communicate our weight to the microbes in our gut, and that obesity can upset the normal microbial balance.

But here is another startling idea: Can the opposite be true as well? Can the makeup of our gut flora affect our weight? To find out, the researchers sucked microbes from the guts of either lean mice or the obese ones. They injected the microorganisms into the intestines of animals whose own innards were unnaturally bare of microbes because they had grown up in a sterile cage.

After two weeks, the mice injected with the “obese” microbes gained roughly double the quantity of fat than those that received the “thin” microbes.

 

Getting specific

gut bacteria
Akkermansia muciniphila | rolandchlapowski.com

Of course, like any discovery in science, this one raises more questions. One of them, is bacteroidetes as a group responsible for the “leanness” of their hosts, or are there specific bacteria that could account for it? A team led by Patrice Cani, who studies the interaction between gut bacteria and metabolism at the Catholic University of Louvain in Belgium, decided to investigate. Lo and behold, they found one bacterium could do the trick all by itself. The bacterium, Akkermansia muciniphila (A. muciniphila), digests mucus and makes up 3–5% of the microbes in a healthy mammalian gut. But the intestines of obese humans and mice, and those with type 2 diabetes, have much lower levels.

Mice that were fed a high-fat diet, the researchers found, had 100 times less A. muciniphila in their guts than mice fed normal diets. The researchers were able to restore normal levels of the bacterium by feeding the mice live A. muciniphila, as well as “prebiotic” foods that encourage the growth of gut microbes.

The effects of this treatment were dramatic. Compared with untreated animals, the mice lost weight and had a better ratio of fat to body mass, as well as reduced insulin resistance and a thicker layer of intestinal mucus. They also showed improvements in a host of other indicators related to obesity and metabolic disorders.

Cani’s team has started unraveling the complicated mechanisms through which the bacterium may influence metabolism. Restoring normal levels of A. muciniphila led to increased intestinal levels of, brace yourself, endocannabinoids. Yes, these are endogenous derivatives of THC, acting as signaling molecules that help to control blood-glucose levels and maintain the gut’s defenses against harmful microbes.

A. muciniphila seems to have a “dialogue” with the cells of the intestinal lining and with the immune system, says Cani, sending a signal that affects the production of anti-microbial molecules, while increasing the production of mucus. It seems as if the bacterium is telling the host that it will take care of any invading harmful microbes in exchange for more food.

 

What does all this have to do with fiber?

Fiber has long been linked to better health, but new research shows how the gut microbiota might play a role in this pattern. Kelly Swanson, a professor of comparative nutrition at the University of Illinois at Urbana-Champaign, and his team found that simply adding a fiber-enriched snack bar to subjects’ daily diets could swing microbial profiles in a matter of weeks.

In a small study of 21 healthy adults with average U.S. fiber intake, one daily fiber snack bar (containing 21 grams of fiber) for three weeks significantly increased the number of Bacteroidetes bacteria and decreased the number of Firmicutes compared with levels before the study or after three weeks of eating fiber-free bars. Such a ratio—of more Bacteroidetes to fewer Firmicutes—is correlated with lower BMI.

 

Bottom line: Will it make us live longer (and healthier)?

That’s what you’d expect from all those beneficial effects. In a recent report in BiomedicalCentral.com, researchers from Harvard School of Public health found that people who reported in surveys a diet rich in cereal fiber lived longer than those who chose less in the morning. It drew from the NIH-AARP Diet and Health Study and included more than 566,000 AARP members aged 50 to 71 from six states and two large cities. It excluded individuals who reported extreme-energy intake, which is common, since scientists believe these survey takers are not totally accurate in what they report. That left them with over 367,000 people. They had a 19% reduced risk of death, compared to those who ate the least amount of cereal fiber.

Crunching the numbers even further, the authors found that high-fiber cereal eaters had a 34% lower risk of death from diabetes and a 15% reduced risk of death from cancer. People who ate a lot of whole grains and dietary fiber had a 17% lower risk of all-cause mortality. I usually don’t put much stock in observational studies based on subjects’ questionnaires. But this one comes with the background of a large volume of carefully controlled experiments in animals and humans, giving it more credibility.

I think that the evidence of the beneficial effects of dietary fiber is becoming undeniable. Of course “more studies are required”, as scientists are wont to say. But Burkitt’s hypothesis is becoming more and more accepted by even the most skeptical investigators.

One person in the audience of Burkitt’s lecture at UCSF wasn’t as skeptical despite the primarily epidemiological observations. The next morning, I fixed myself a lush fiber breakfast (see picture below), and 30+ years later I haven’t veered one iota, despite good-natured ribbing from my family. And I am still here to tell the tale.

Which reminds me of the old Yiddish appellation of alter kacker (old sh..ter), the equivalent of old fart. Except that with all the recent poop science, it has acquired a less dismissive, much deeper meaning. So, here is to fiber, poop, and old farts.


Featured photo credit: Jan Vašek

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