Chapter 173
Fecal Transplantation
Gerontologists have good reason to assume that age-related changes in the microbiome are more causal than merely playing an accompanying role, because fecal transplantation studies, which I describe in detail at see.nf/transplant, show that the lives of old animals can be extended when they receive intestinal bacteria from younger animals. The stool of centenarians has anti-aging effects when it is fed to mice. Scientists gave mice, on the one hand, the feces of a 70-year-old person, which contained Bilophila wadsworthia, a pro-inflammatory bacterium that thrives on a diet high in animal products, and on the other hand the feces of a 101-year-old person, whose stool contained more bacteria that feed on fiber. In the mice that were transplanted with the microbiome of the person over 100, a number of youthful physiological indicators appeared, such as fewer age pigments in their brains. This opens up the possibility of one day using the feces of centenarians to promote healthy aging. Why bathe in the blood of virgins when you can feast on the feces of the venerable?
Dysbiosis
An unhealthy disturbance of the balance of the gut flora can arise from too little fiber or too much antibiotics, salt, protein, and certain food additives.
Plugging leaks with fiber
One of the mechanisms by which gut dysbiosis accelerates aging is a leaky gut wall. You can see more on this at see.nf/leaky, but basically it is known that in all animal species the tightness of the intestinal barrier decreases with age. This can cause unwanted tiny particles of undigested food, microbes, and toxins to slip through the intestinal lining and enter the bloodstream, where they trigger chronic systemic inflammation. Luckily, we can do something about it.
To prevent gut dysbiosis, inflammation, and leakiness, you should above all eat plants. The reason that vegetarians tend to have a balanced microbiome, higher bacterial biodiversity, an intact intestinal barrier, and significantly fewer uremic toxins forming in the gut is probably that fiber is the most important food for a healthy gut microbiome. Cause and effect were demonstrated in a randomized double-blind crossover study using pasta with versus without added fiber.
Other ways to heal a leaky gut (for details see see.nf/sealthegut) are: not drinking alcohol, not taking NSAID medications such as aspirin, ibuprofen, and naproxen, which can lead to damage to the gastrointestinal lining within five minutes, and (see see.nf/leaky) taking the amount of zinc daily that is contained, for example, in a cup of cooked lentils.
Dysbiosis, inflammation, immunosuppression
The most important role a healthy microbiome probably plays in maintaining health in old age is that it prevents systemic inflammation. Inflammaging, the inflammatory state of the entire organism, is a strong risk factor not only for premature death. People who, for their age, have above-average levels of inflammatory markers in the blood are hospitalized more often, are frailer, less independent, and suffer from a variety of diseases, including the usual infections.
For example, in Japan more than 40 percent of all centenarians die of pneumonia and other infectious diseases. In one of the largest studies with almost 36 000 centenarians in Great Britain, pneumonia was the most common identifiable cause of death. Inflammaging not only increases susceptibility to developing the most common cause of bacterial pneumonia, but older adults with more inflammation generally also become more severely ill and are more likely to die.
As we get older, our immune-system macrophages (from the Greek, “giant eater cells”) lose their ability to enclose and destroy bacteria. The same thing happens in normal mice. But mice raised germ-free have no leaky gut, no resulting inflammation, and no loss of macrophage function. To establish the connection between inflammation and this loss of function, researchers showed how impairment of macrophages in germ-free mice can be triggered by infusion of an inflammatory mediator that in the Petri dish directly hampers the macrophages’ ability to kill pneumonia bacteria. Since our immune system is also responsible for cancer defense, their failure, caused by inflammation due to dysbiosis, is likely one reason why cancer incidence rises so steeply with increasing age (and why germ-free mice get fewer tumors and live longer).
Eat as few antibiotics as possible
What can we do, besides eating enough fiber, to prevent dysbiosis? There are a number of factors that disrupt the balance of the microbiome. For example, in Western countries, on average two and a half doses of antibiotics per 100 people are taken each day. The devastating damage that this causes in the microbiome may explain why taking antibiotics increases cancer risk, although confounders that correlate with both—such as smoking—may also play a role in this context.
Up to three quarters of antibiotic use is of questionable therapeutic value. Avoiding unnecessary antibiotic use and instead using targeted agents with a narrow spectrum of activity protects the gut flora, but most people probably do not even realize that every day, with the meat, dairy products, and eggs they eat, they also ingest antibiotic residues. In the United States, up to 80 percent of the antibiotics used are not used to treat sick people, but are fed to livestock, in part as compensation for the miserable housing conditions that today characterize much of the modern agribusiness industry. But do enough antibiotics end up on our plate to matter?
Infections with multidrug-resistant bacteria are on their way to becoming the world’s most common cause of illness and death by 2050, overtaking even cancer and heart disease. Excessive antibiotic use can cause our gut to be colonized by such superbugs, so researchers set out to calculate how many animal products one would have to eat until the antibiotic concentration in the gut allows resistant bacteria to gain the upper hand. A serving of beef, chicken, or pork contained enough tetracycline, ciprofloxacin, tilmicosin, tylosin, sarafloxacin, and erythromycin to promote the growth of resistant bacteria. One and a half servings of fish (150 g) contained more than the Minimum Selective Concentration (MSC) of ciprofloxacin and erythromycin. Two cups of milk were the tipping point for tetracycline, ciprofloxacin, tilmicosin, tylosin, and lincomycin. And: With erythromycin and oxytetracycline, the legally permitted amounts in two eggs can exceed the levels that are considered safe for health.
Most multidrug-resistant bacteria have mobile genetic elements, so-called plasmids, small DNA rings that carry the resistance genes that they can pass on to other bacteria, including those in the human gut. In a gut model, the transfer of an antibiotic-resistance plasmid from E. coli bacteria from a chicken to human gut bacteria occurred within two hours. This is presumably why the burden of antibiotic-resistance genes in people who eat a purely plant-based diet is significantly lower than in omnivores or ovolactovegetarians. In egg, poultry, and fish eaters, a higher incidence of resistance genes was found even against vancomycin. Vancomycin is an antibiotic used as a last resort to treat severe, life-threatening streptococcal and staphylococcal infections, including infections with multidrug-resistant Staphylococcus aureus (MRSA).
We have to stop wasting life-saving wonder drugs to accelerate the growth of livestock under unhygienic conditions, and we also have to end the careless, overly frequent use in medicine. But sometimes you have to take antibiotics. A series of studies in mice suggests that we can protect our microbiome from harm by making it more resilient with a healthy diet and, for example, eating more fiber and less sugar. Prebiotics protected mice under antibiotic treatment from colonization by the harmful bacterium Clostridium difficile, and a higher-fiber and lower-fat diet protected other mice from dying of postoperative sepsis that had become possible because the microbiome was disrupted by antibiotics.