Unpacking the Mysteries of the Microbiome

In the past decade it has become well recognized that the millions of bacteria in the gut, collectively known as the microbiome, can influence the health of the brain, lung, heart, metabolism and the immune system. Thousands of studies have been conducted since the term was first introduced in 2001, with research shifting from an early focus on cataloging microorganisms in the human microbiome to pathogen identification and now to understanding their functional roles and how they interact with the host. Following are some of the key learnings to date, including a conversation with a leading microbiome researcher on behalf of our Well Read Patient readers. Please keep in mind that microbiome research is still in its infancy, and probiotic/prebiotic treatments are not the standard of care at this time.

What exactly is the microbiome?

Scientists define it as the sum of the microorganisms (bacteria, viruses, fungi, etc. that live in the body in healthy conditions), their genetic information, and their ecological niches. The microbiome is spread across different organs and tissues of the human body, but the most important and best studied is the gut microbiome. Studies show that under normal conditions, formation of the adult gut microbiome occurs over the first 3 years of life and is affected by events such as birth method, cessation of breastfeeding and starting solid food. Over time, it is thought that diet, drugs, age, smoking, exercise and host genetics affect the composition of the gut microbiome, and that some of these changes may contribute to metabolic, neurological, and immune disorders.

A high fiber, low animal fat diet may have beneficial effects on the gut microbiome.  With this in mind, the principle of “You are what you eat” is further clarified as “You are what your gut microbes do with what you eat,” according to the European Society of Neurogastroenterology & Motility. This is precisely the area that has long fascinated Christopher Damman, MD, a gastroenterologist who has studied the microbiome’s role in health and disease for the past two decades.

“While there are many ways to consider the role microbes play in our health, most essentially they activate or transform components of food that the body can’t process by itself,” he explains. “The microbiome converts polyphenol, the colorful compounds that occur naturally in plants, and fiber, a carbohydrate prebiotic that resists host digestion, to metabolites, which are molecular byproducts of digestion. These in turn influence the mitochondria, our cells’ metabolic powerhouses, that generate most of the energy needed for the cell to function.”

Metabolites also underly the gut’s natural production of hormones GLP and GLP-1, best known for its use in weight loss and type 2 diabetes drugs like Wegovy and Ozempic. Together, with another lower gut hormone called PYY, they help coordinate the body’s response to food by regulating appetite and blood sugar.

The traditional focus has been on therapeutic use of live microbes to repopulate the gut; for some, however, says Dr. Damman, there may be more power in postbiotics. “It can be very difficult to repopulate the microbiome of individuals whose guts may resemble a bleached coral reef as opposed to a vibrant aquarium, by just increasing intake of prebiotics through whole foods. The next best approach may be to therapeutically provide the metabolites naturally produced by a healthy gut microbiome,” he says.

While the gut responds to everything in your environment, from exercise to stress levels, food appears to be disproportionately important, asserts Dr. Damman. “The key to fostering a healthy microbiome may focus on four nutrients: fiber, phenols, bioactive fats, and ferments.” To that end, he has created a tool to help guide people to microbiome-friendly choices by assigning a Nutrient Consume Score (NCS) from one to 100 for a wide range of foods. Based on an algorithm that promotes increased fiber, phytonutrients, bioactive fats and potassium, and decreased amounts of simple carbs, additives, saturated fats and sodium, NCS is available as a prototype online at Dr. Damman’s website gutbites.org.  An app is in development that will enable easier use, such as scanning UPC codes at the grocery store. “I believe this is the first microbiome-focused nutrient calculator, and my intent is to have it validated scientifically and clinically before a beta release, possibly by early next year,” he says.

The takeaway from all this is deceptively simple. “We have gone on these really interesting, complex journeys intellectually, but at the end of the day, we return to our original understanding of healthy eating,” muses Dr. Damman. “As Michael Pollan (influential best-selling author and fellow at the Radcliffe Institute for Advanced Study at Harvard) says, eating mostly plant-based food, and not too much, is the way to go. All the research on the microbiome, metabolites, mitochondria, bioactives, etc. points in screaming ways right back at something we’ve known all along. We’ve evolved over centuries in concert with our microbiome and healthy whole foods that naturally regulate our appetites.”

In terms of preventing obesity, diabetes and metabolic disease, Dr. Damman maintains: “There’s no substitute for a healthy diet complemented by mindfulness, movement, and adequate sleep.”

New Tools, New Strategies for Gut Microbiome Therapy

Initially, gut microbiome therapies ranged from probiotics and prebiotics to fermented foods and fecal transplants.

But these are still early days, and new approaches are continually under the microscope, including:

  • According to research from Nature Aging, in healthy individuals the microbiome can continue to change after age 50, in contrast with a static microbiome composition seen in people who are less healthy and die earlier. Of particular note is the finding that each person’s microbiome becomes more distinct as they age, emphasizing the ineffectiveness of a ‘one size fits all’ approach and influencing the need for personalized health therapies.
  • Mayo Clinic’s recently announced Gut Microbiome Wellness Index 2, a tool designed for healthcare practitioners to identify adverse changes in their patients’ gut health before serious symptoms arise. By screening a gut microbiome sample, the tool can predict with 80% accuracy or greater whether a person’s gut is healthy or trending toward a diseased state. The ability to detect shifts in gut health was tested in various clinical scenarios, including people who had undergone fecal microbiota transplantation, or had made changes in dietary fiber intake, or who had antibiotic exposure. Additional testing is in progress.
  • New technologies that allow physicians to more easily examine the small intestine and upper part of the colon are sure to shine a bright light on these often neglected areas of microbiome research, according to Dr. Damman. Most exciting is the recent launch of swallowable devices with compartments that open up when certain acidity levels are reached to sample the small intestine. “This could be a real breakthrough for exploring how to best help those with small intestinal bacterial overgrowth (SIBO), Crohn’s, irritable bowel syndrome (IBS) and other conditions who frequently experience significant gastrointestinal symptoms from macro nutrient-rich diets.” Future possibilities may include partnering small intestine bacteria with their preferred prebiotics and personalized combinations of prebiotics.

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