The Lucky Years: How to Thrive in the Brave New World of Health (19 page)

Earlier I noted how mitochondria, the energy source in our cells, were once free-living bacteria that somehow ended up getting incorporated into our physiology to power life. It turns out that we owe our life—and health—to more microbes than we ever imagined before. In fact, one can argue we owe our life more to these microbes than to our own DNA from a numbers standpoint: they outnumber our own cells by a factor of about 10 and include more than eight million genes. That amounts to more than 300 times the number of genes we contain in our own DNA. Luckily, our cells are much larger, so the microbes don’t outweigh us 10 to 1. These microbes are found everywhere, inside and out. They cloak our mouth, nose, ears, intestines, genitalia, and skin. Scientists have so far identified some ten thousand species of microbes, including many that have never been documented before, but that number of species will probably climb and could approach thirty-five thousand. New technologies are emerging to help us identify all species, many of which cannot be cultured traditionally in a laboratory and demand high-tech DNA sequencing to identify.

Most of these organisms make their home within our digestive tract, and while they include fungi and viruses, the bacterial species have starring roles in supporting our health. And we interact not only with these microbial organisms but also with their genetic material. The two million unique bacterial genes found in each human microbiome can make the 20,000 to 25,000 protein-coding genes in our cells seem almost negligible by comparison. Indeed, we are more microbial than human.

Even our own DNA has codes of viral origin. Throughout our evolution, viruses have inserted themselves into the human genome, and some could be responsible for our illnesses. Recent studies, for example, suggest that the deadly muscle degenerative disease amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, could be associated with remnants of an ancient virus that entered our genome thousands of years ago. Although this research is just beginning, and a lot more needs to be understood—including environmental factors in the
expression of genes that lead to the disease—the takeaway is that we’re not just made up of human cells. We are an intricate web of microbial components that have a say in our lifelong biology.

As I mentioned earlier, the microbiome is our term for the complex microbial world that thrives outside of our own cells, but still within us (
micro
for “small” or “microscopic,” and
biome
referring to a naturally occurring community of flora occupying a large habitat—in this case, the human body). Although the human genome is almost the same in every individual, give or take the genes that encode things like certain physical characteristics, risk factors for disease, and blood type, even identical twins can have hugely different gut profiles. The state of the microbiome is turning out to be so key to human health that it may actually be considered an organ in and of itself. And how we feel, both emotionally and physically, may hinge on the state of our microbiome. The NIH Human Microbiome Project started in 2008 as an extension of the Human Genome Project to catalog these microorganisms living in our body, and our appreciation for the influence of such organisms has grown rapidly with each passing year.
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Our growing knowledge about the microbiome comes from studying mice that have been altered so that they do not have any gut bacteria. This allows scientists to study the effects of missing microbes, or to expose the “germ-free” mice to various strains of bacteria and record changes in behavior. Germ-free lab rats have been shown, for example, to exhibit severe anxiety or have chronic gut and general inflammation, the latter of which is a huge risk factor for virtually every disease.
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The studies on the impact artificial sweeteners can have on the microbiome, for instance, are among the many finally exposing the power these microbes can have in our own physiology and what can happen when their healthy balance is disrupted or otherwise compromised. Scientists have also documented a “diabetes fingerprint,” a specific array of gut bacteria that correlates with the disease. Researchers can now manipulate gut bacteria in animal models, resulting in better blood sugar control and insulin sensitivity (important for controlling and even reversing type 2 diabetes). With more than 29 million Americans suffering from diabetes,
this finding provides an incredible opportunity for both preventing and treating the disease, as well as addressing its complications, which include serious neurological conditions such as nerve damage, blindness, and dementia. About half of all Americans are affected by diabetes: they either have the metabolic disorder or are prediabetic.

In 2015, for another example, the journal
Nature
reported on the deleterious effects dietary emulsifiers have on the microbiome, at least in mice.
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Emulsifiers are molecules that act as blending agents in food products that contain otherwise unmixable ingredients such as oil and water. They are ubiquitous in processed foods, including ice cream, salad dressing, and cream cheese. Look for names like carrageenan, lecithin, polysorbate 80, polyglycerols, guar gum, locust bean gum, carboxymethylcellulose, and xanthan gum in the packages you buy. Lecithin is actually nature’s emulsifier; it’s found in egg yolks and soy and is responsible for giving mayonnaise its creamy consistency.

Emulsifiers are also added to foods to extend their shelf life, improve texture, and keep ingredients from separating. In recent decades, there has been a significant increase in the number of people with metabolic syndrome and inflammatory bowel disease. Metabolic syndrome is not a disease in itself, but rather a group of risk factors that includes obesity, type 2 diabetes, and cardiovascular events such as heart attacks and strokes. Inflammatory bowel disease refers to inflammatory conditions of the colon and small intestine, such as ulcerative colitis and Crohn’s disease. All of these illnesses are associated with changes in gut microbiota and, in turn, affect one’s digestion.

Researchers have long been puzzled by the rising incidence of these illnesses, which can’t be due to human genetics because that hasn’t changed much in recent decades. This conundrum is what inspired Andrew Gewirtz, a biology professor at Georgia State University, to look for external environmental factors contributing to the increase. He and his colleagues used two groups of mice. One group had abnormal digestive systems that were predisposed to colitis, or inflammation of the colon. The other group had healthy digestive systems. When emulsifiers were given to the predisposed mice through water and food, the mice
developed chronic colitis. The healthy mice developed low-grade intestinal inflammation and a metabolic disorder that caused them to eat more, becoming obese, hyperglycemic, and resistant to insulin.

Emulsifiers appear to disrupt the mucous layer that protects the intestinal tract, allowing for the movement of bacteria and increased inflammation as the body reacts to the bacteria being in the wrong place. The inflammatory response, in turn, interferes with satiety, or knowing instinctively when one has eaten enough. This, they theorize, caused the mice in the study to overeat and get fatter. Human studies are planned to see how much these emulsifiers are contributing to the obesity epidemic. Tests are also underway to determine if the natural emulsifier lecithin has the same effects as the chemical ones do.

Studies like that are just the beginning. Overall, what the latest science tells us is that our intestinal organisms participate in a wide variety of physiological actions, including immune system functioning, inflammation, hormonal functions, neurotransmitter and vitamin production, digestion and nutrient absorption, and detoxification. They help dictate whether we feel hungry or full, and how we utilize carbohydrates and fat. All of these processes factor into whether or not we develop conditions as diverse as diabetes, cancer, depression, or dementia. The microbiome affects our mood, libido, metabolism, immunity, and even our perception of the world and our thinking processes. Some of the latest science is showing that a disease long thought to be rooted in the brain—depression—may actually come from the gut, as well as depression’s kissing cousins: chronic anxiety, insomnia, excessive worry, and obsessive-compulsive disorder (OCD).
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It turns out that our feelings are largely controlled by the balance of bacteria in our gut and how they impact our brain via the vagus nerve, which connects the two. Suffice it to say this gives a whole new meaning to “gut feelings”; the ever-prescient Hippocrates noted centuries ago that there’s an association between what you eat and how you feel.

Even our sleep can be impacted by these invisible bugs, which isn’t all that surprising when you consider the fact that gut bacteria and sleep both play into our health in profound ways.
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Here’s the connection:
Specialized biological molecules called cytokines are required to bring on sleep, particularly deep, restorative sleep. New research is showing that gut bacteria stimulate production of these chemicals in sync with cortisol levels. You’ve probably heard of cortisol, our body’s main stress hormone. Levels of this hormone are tied to our circadian rhythm, changes in the body that follow a roughly twenty-four-hour cycle, responding primarily to light and darkness in the environment. Such changes determine whether we’re feeling alert or tired. Cortisol should be lowest at night and begin to rise in the early morning hours. So these cytokines essentially have circadian cycles dictated by the gut bacteria. In the morning, when cortisol levels go up, these cytokines are inhibited, which defines the transition between sleep phases. Disruption of the gut bacteria can have major negative effects on sleep and circadian rhythms.

Let me give you one more wild example. Surgical approaches to weight loss, such as gastric bypass to physically change the digestive system, have become increasingly popular solutions to obesity. These procedures often involve making the stomach smaller and rerouting parts of the small intestine. We used to think that they triggered rapid weight loss largely by forcing the person to eat less, but another landmark study published in
Nature
in 2014 showed that the microbiome contributes to the success of gastric surgery.
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A major portion of the weight loss is attributable to changes in the gut microbiota, changes that occur after surgery in response to not just the anatomical adjustments but the dietary shifts that typically happen as the person consumes foods that favor the growth of different bacteria. These patients often see a reversal in their diabetes as well soon after surgery, and I bet that part of that is also due to the changes in the composition of the gut bacteria.

A 2012 study published in
Science
found a link between a certain strain of bacteria (
E. coli
) disturbing the intestinal microbiome and causing colorectal cancer:

Ecologists have long known that when some major change disturbs an environment in some way, ecosystem structure is likely
to change dramatically. Further, this shift in interconnected species’ diversity, abundances, and relationships can in turn have a transforming effect on the health of the whole landscape—causing a rich woodland or grassland to become permanently degraded, for example—as the ecosystem becomes unstable and then breaks down the environment. For this reason, it should come as no surprise that a significant disturbance in the human body can profoundly alter the makeup of otherwise stable microbial communities coexisting within it and that changes in the internal ecology known as the human microbiome can result in unexpected and drastic consequences for human health.
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Once again, we see the power of context. Bacteria were earth’s first inhabitants. In 2013, the oldest signs of life on earth—3.5 billion years old—were discovered in a remote region of northwest Australia, where evidence of a complex microbial ecosystem is locked in ancient rock formations. It was part of our evolution to forge a symbiotic relationship with bacteria.

The science of understanding the microbiome is still in its infancy, but I expect it will explode in the coming decade. We’ll soon begin to understand how different microbiotic profiles, much like genetic profiles, are related to certain diseases or to optimal health. And we will begin to learn how we can leverage the microbiome to prevent and treat a variety of ailments, from neurodevelopmental challenges in early life to neurodegenerative problems and chronic illnesses in later life. You’ll be able to figure out whether your gut is harboring tribes that code for wellness or, conversely, sickness. And you will be able to make targeted tweaks to your diet and daily habits to support the growth and maintenance of the right kind of microbes for you. You may think that you’re doomed to have
X
,
Y
, and
Z
due to your genetics, but in the Lucky Years your fate will hinge more on how you play the cards you’ve been dealt through how you live than on solely which cards you hold.

All this goes to show that it’s not all about human DNA, but about the microbiome, too. Our context comprises this dynamic duo. They
may even complement each other in unexpected ways. For example, fully one-fifth of all genes in blood cells undergo seasonal changes in expression. This was just discovered during an elegant study performed by a couple of scientists at the University of Cambridge. They found that in the winter, your blood has a denser mix of immune responders.
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And in the summer months, your blood contains more of the hormones that help the body to burn fat, build tissues, and retain water. These seasonal changes could offer insights into inflammatory diseases such as hypertension and autoimmune diseases such as type 1 diabetes. And such seasonal changes also occur in the microbiome, which in turn impacts health and risk for illness. Perhaps we will soon know, by virtue of the month or time of year, which genes are turning on and which microbes are dominating. This information can then tell us, in real time, what risks we face and which behaviors we should embrace to optimize our genetic and microbial machinery.