Chapter 171
Prebiotics and Postbiotics
The most abundant microRNA in milk is microRNA-148a, an important inhibitor of the key suppressors of the aging enzyme mTOR, which I discussed in the chapter “Eleven Ways to Slow Aging.” After all, what would an infant need more than accelerated aging? This is even more striking in dairy cows, since their newborns double their birth weight in 40 days, more than four times as fast as human infants. Cows have been selectively bred for high milk production, which appears to have led to the excessive expression of microRNA-148a.
Species-specific growth stimulation programmed by milk microRNA was actually intended only for infancy. With continued exposure to growth-promoting exosomes from pasteurized milk, there is a considerable risk to be feared for the development of chronic diseases—from acne and obesity to diabetes and cancer. For example, microRNA-148a directly stimulates the growth of prostate cancer in vitro, and presumably for that reason, dripping milk onto human prostate cancer cells also accelerates their growth rate by more than 30 percent. Perhaps that is why a systematic review of observational studies found that the overwhelming majority of them—19 out of 20—identified an association between milk consumption and increased prostate cancer risk. MicroRNA-21, one of the first cancer-promoting “oncomiRs” discovered, is also a characteristic dairy-milk microRNA.
Perhaps microRNAs could also explain the difference in mortality associated with fresh versus fermented milk in two large Swedish studies. Drinking fresh milk was associated with a significant increase in mortality risk in men and women, but not consuming fermented milk. Fermentation of milk by bacteria can deactivate exosomes and microRNA, which, however, apparently does not affect prostate cancer risk, which seemed to be elevated with both milk and yogurt consumption.
Recently, an article titled “Cow’s milk could deliver harmful, undiscovered cargo to humans” proposed reconsidering consumption recommendations for dairy products, since an estimated 35 trillion bovine exosomes are floating around in every glass of milk. In view of the role of exosomes in pasteurized milk in ramping up mTOR activity, some researchers concluded that “milk exosomes should not enter the human food chain,” because milk “is not a suitable food for adults.” In other words: milk is for babies.
Prebiotics and Postbiotics
The human colon may be the biologically densest ecosystem in the world. Although many believe our stool consists mainly of undigested food, about 75 percent of it is pure bacteria—trillions upon trillions of them, about half a trillion bacteria per teaspoon. Or as the well-known science journalist Neil deGrasse Tyson once put it: “In one linear centimeter of your lower colon live and work more bacteria than all the people who have ever lived.”
Do we get anything out of these trillions of tenants that inhabit our colon, or are they just hanging out? They pay rent by strengthening our immune defenses, producing vitamins for us, improving digestion, and keeping hormones in balance. We house and feed them, and they maintain and protect their dwelling, our body. Prebiotics are the food of beneficial bacteria. Probiotics are the beneficial bacteria themselves. Postbiotics are what these bacteria produce.
Gut bacteria are also called the “forgotten organ”; they are as metabolically active as the liver and weigh as much as a kidney. They regulate up to 10 percent of the metabolic products in the bloodstream. Each person has about 23 000 genes, but all gut bacteria together have about three million. About half of all the cells in our body are not human cells. In reality, we are a superorganism—a kind of “human-microbe hybrid.”
From the study of stool samples from around the world, from people with different eating habits, and from fraternal versus identical twins, we know that diet plays the most important role in determining the gut microbiome. When you change your diet, you change your gut flora, after days or weeks, toward health or disease.
The good and the bad gut bacteria
The relationship between us and our gut flora, which over millions of years of evolution developed together with us and our ancestors, is so close that it affects most of our physiological functions. Nevertheless, the microbiome is probably the most adaptable part of our body. Gut bacteria such as Escherichia coli (E. coli) can divide every 20 minutes. The over ten trillion bacteria that we produce daily can therefore respond very quickly to changed living conditions. With every meal, we have the opportunity to give them a nudge in the right direction.
Thousands of years ago, Hippocrates is said to have stated that all diseases originate in the gut, or even more ominously: “Death sits in the gut.” However, he also believed that women were hysterical because of their “wandering uterus.” (Hysteria comes from the ancient Greek hystéra, “uterus.”) So much for the wisdom of ancient medicine. Then the pendulum swung to disbelief—the medical community refused to recognize the intestinal bacterium Helicobacter pylori as a cause of stomach and intestinal ulcers. Out of frustration, one of the discoverers drank a concoction made from the bacteria from one of his ulcer patients to prove the point, before he was finally validated in 2005 with the Nobel Prize for his discovery.
Then the pendulum swung back, in a way, in the form of exaggerated, casually tossed-off causal claims about the role of the microbiome in a wide variety of different diseases. Perhaps the boldest claim of this kind goes back to Elie Metchnikow, who proclaimed that senility and the infirmities of old age were caused by “autotoxins of putrefaction bacteria” that would escape from the colon. He was the first to emphasize the importance of the gut microbiome for aging. He attributed healthy aging to intestinal bacteria that ferment carbohydrates into beneficial metabolic end products such as lactic acid, and linked unhealthy aging to putrefaction—the process by which bacteria break down proteins and, as waste products, generate harmful metabolites.
Throughout history, there has been no shortage of crackpot quacks with crazy medical theories, but Metchnikow was no crackpot—he became Louis Pasteur’s successor, coined the terms gerontology and probiotics, and received the 1908 Nobel Prize in Medicine, going on to become the “father of cellular immunology.” More than a hundred years later, certain aspects of his theories about aging and the gut are now being confirmed.
Young in the belly
It is said that full-term, vaginally delivered, breastfed babies get the gold standard for a healthy microbiome, which then diverges with increasing age. The microbiomes of children, adults, older people, and centenarians show a tendency to cluster, so that a “microbiomic clock” can be derived from them. Dozens of different classes of bacteria in the gut change with increasing age so reliably that our age can be estimated from a stool sample with a margin of error of about six years. If it turns out that these changes play a causal role in the aging process, perhaps the high-tech toilet of the future will also be able to predict our lifespan.
The transition from adulthood to old age is accompanied by pronounced changes in the microbiome. Given the great differences among people, there is no “typical” microbiome of older individuals, but the trends go exactly in the direction Metchnikow described: from fermenting fiber to the fetid decomposition of proteins. This shift from beneficial bacteria to harmful ones goes hand in hand with increasing permeability of the intestinal wall, the release of bacterial toxins into the bloodstream, and a cascade of inflammatory effects. That led to the hypothesis that this change in the microbiome is a “main cause of age-related diseases and the resulting premature death of older people.”