“Happiness is not a matter of intensity but of balance, order, rhythm, and harmony.”
Thomas Merton
Today is January 1, 2020—the start of a new, and hopefully, happy year. Chances are, however, that you’ve given little, if any, thought to the microbes that share your body surfaces, referred to as your microbiome, in determining your level of happiness. Unless, that is, you are a microbiome researcher.
If you are among the rapidly growing number of microbiome researchers, then you not only are aware of the pivotal role that these microorganisms plays in health and disease, but you’re brimming with enthusiasm over anticipated discoveries. Just as science was on the threshold of incredible discoveries in the late 19th century when the “germ theory of disease” surfaced, we are again poised for astonishing revelations about the “germ theory of health.”
What is the human microbiome? More than a century ago the conceptual framework was established for understanding that germs contribute both to health (eubiosis) and cause disease (dysbiosis). But it was at the turn of this century that the Nobel Prize-winning immunologist Joshua Lederberg used the term microbiome to describe “an ecological system of commensal, symbiotic, and perhaps pathogenic microorganisms that reside in the human body.” (All other animals as well as plants also are colonized by huge numbers of microbes that constitute their microbiomes.)
A foundational development that allowed the field of microbiome research to flourish was the work in the late 1970s of Carl Woese on metagenomics—the direct genetic analysis of genomes contained within an environmental sample. This technology allowed the characterization of microbes (bacteria, archaea, fungi, viruses, and protists) in all sorts of environments without the need to culture (grow) them in the laboratory. Because more than 99% of microbes can’t be cultured, metagenomics opened our eyes to a mindboggling number of microscopic creatures.
A key initiative that ignited an explosion of research on the human microbiome was the Human Microbiome Project launched by the National Institutes of Health in 2008. The project set out to determine the contributions to human health and disease of microbes colonizing five body surfaces: gastrointestinal tract (or gut), oral cavity, lungs, skin, and vagina. While the discoveries of scientists exploring each of these ecological niches are intriguing, the most amazing findings have come from those focused on the gut. And it is these microbes that appear to figure most importantly into whether you’re feeling happy or sad.
Nature of the gut microbiome. Most of the microbes living in your gastrointestinal tract reside within the large bowel or colon. It is estimated that in total they weigh about the same as your brain, roughly two pounds. Given the current understanding of its profound importance to human health, many researchers propose that the gut microbiome should be considered a vital organ.
Your gut harbors about 40 trillion bacteria, which outnumber the 37 trillion cells in your entire body. While the human genome is composed of about 20, 000 genes, the gut contains a 100-fold greater number of bacterial genes. While bacteria have been the most studied group of microbes in the gut, they are outnumbered by viruses (the virome). And an untallied number of fungi (the fungiome), archaea, and protists also make the colon their home.
To me one of the most impressive things about microbiome research is the willingness of investigators in this field to deal with complexity. Not only do they have massive numbers of microbes to consider, but metagenomic studies have revealed an incredible diversity (for example, about 2,000 bacterial species are found in the healthy gut microbiome).
How on earth, I ask myself, can the contributions of this array of microbes to health and disease be sorted out? Yet, preliminary studies have revealed correlations between the gut microbome and obesity, type 2 diabetes, inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), irritable bowel syndrome, cardiovascular disease, colon cancer, asthma, allergies, and autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus.
But correlation doesn’t mean causation, and so far a robust causal relationship between the composition of the gut microbiome and human disease has been established only with the infection Clostridioides difficile colitis. This clinical entity and its treatment were discussed in germgems blogs on September 22 (Why C. diff should be a Household Name) and November 24 (The Latest Poop on Fecal Microbiota Transplantation).
The Gut-Brain Connection. One aspect of gut microbiome research that has captured increased attention in recent years is its involvement in behaviors thought to be exclusively under the control of the brain. Germs in your gut are nourished by the food you consume, and animal studies suggest that gut bacteria may actually influence your food choices. (So is my hankering for foods like cakes and cookies influenced by some bacterial species in my gut microbiota? Potential involvement of the microbiome in obesity was discussed in the August 5 blog “Obesity: Are Germs to Blame?)
What we do know now, however, is that there is a rich route of communication between your gut and your brain via your autonomic nervous system. For example, neurochemical signals released by nerves connected to your gut can affect your mood, making you happier or less happy, relaxed or anxious, sleepy or alert, hungry or full. More than 50% of dopamine and serotonin, the body’s natural mood enhancers, are actually produced in the gut.
The impact of the gut microbiome on human cognition, sleep, eating and mood disorders, and in poorly understood illnesses such as chronic fatigue syndrome (CFS) and autism is unclear but under study. (The gut microbiota of patients with CFS has been found to differ from that of healthy controls. And people with autism are much more likely than others to have gastrointestinal problems.)
Emeran Mayer, a UCLA neuroscientist and gastroenterologist, suggests in his recent book The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Overall Health, that “The connection between our gut and our mind is not something that solely psychologists should be interested in; it’s not just in our heads.”
Some of the most provocative evidence that gut bacteria can influence emotions has emerged from studies in mouse models of depression. In one study, the bacterium Lactobacillus, which is typically found in yogurt, was found to play a critical role in modulating metabolites associated with depression. Animal studies like this underlie the thinking behind attempts to treat depression in humans with fecal microbiota transplants.
Currently, most of the claims regarding how your gut microbiome can affect your emotional as well as physical well-being are extrapolated from studies in animals. With increasing recognition of the potential role of the human microbiome in health and in diseases for which improved treatments are desperately needed, profiling of the gut microbiome is becoming big business. But, as was underscored by Susan Lynch and Oluf Pedersen in their 2016 New England Journal of Medicine review: “The Human Intestinal Microbiome in Health and Disease,” we need to be cautious until evidence is provided by properly controlled studies in humans.
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