WHAT IS THE MICROBIOME
The microbiome is a series of communities containing trillions of microorganisms including bacteria, viruses, fungi, and other less well studied micro- organisms such as archaea and eukaryotes. While the gut microbiome is most commonly discussed, microbiomes are present in all spaces that connect with the outside world, including the skin, the digestive tract, the nose, the mouth, the vagina, and the conjunctiva of the eye. The human metagenome refers to the collective genomes of resident microorganisms and the approximately 24000 human genes. There are roughly 1000 species of bacteria in the body with about 2 million bacterial genes. We are constantly growing and excreting microbes. About 30% of the solid matter of our stool consists of microbes.
FUNCTION OF THE MICROBIOME
Microbiome has wide range of functions. In the gut it plays an important role in producing digestive enzymes and degrading dietary components. Vitamins including B vitamins and vitamin K involved in clotting are synthesized by the microbiome. Local mucosal immunity withing the gut and systemic immunity are shaped by the microbiome. Bacterial colonization of the body provides resistance towards pathogenic bacteria. Even memory and emotional states are impacted by the microbiome. Gut bacteria make about 90% of the body’s supply of serotonin, which impacts both mood and gastrointestinal function (1).
FACTORS SHAPING THE MICROBIOME
The gut microbiome is heavily influenced by the first 3 years of life. Significant events include vaginal delivery versus C-section, breast versus bottle feeding, and the presence of a pet. Various factors throughout our life continue to shape the microbiome including sleep (2), stress, nutrition (3), medications (4), and environment. In regards to non-antibiotic medicines the relationship to the gut microbiome is bidirectional. Some gut bacteria store medicines and other increase or decrease their potency. Medications alter the growth rate of certain bacteria and in other cases increase or decrease their production of bioactive compounds such as neurotransmitters. A compelling recent study on nutrition and the microbiome showed that consumption of fermented foods but not high fiber foods can increase the diversity of the microbiome and lower systemic inflammatory markers (5).
While it is likely that increased diversity of the microbiome correlates to decreased inflammation in the body and improved health, our understanding of a healthy microbiome is limited. Microbiome studies use a range of methods for specimen collection, different methods of analysis, and focus on the industrialized world. Correspondingly, it is difficult to compare studies or generalize conclusions from a single study group to a wider population (6).
THERAPEUTICS BASED ON ALTERING THE MICROBIOME
Numerous small studies have demonstrated the potential impact of the microbiome on depression, weight management, cardiovascular disease, autoimmune disease, and aging. A study of fecal transplant from old mice or old humans to young mice showed accelerated age-related changes in memory (7). Fecal transplant from young mice to progeroid mice, mice with genetic alterations that mimic aging, extended lifespan and healthspan (8). An 8 week study of 2 people with severe depression showed significant improvements in depression with fecal transplants that were not seen in the 2 people in the placebo arm.
SUMMARY AND COMMENTARY
The microbiome consists of trillions of micro-organisms in the body that influence a wide range of functions from immune function to mood. Multiple factors including nutrition and medications shape our microbiome. That being said, we are at the very beginning of our understanding of the microbiome. In particular, there is sparse data looking the viruses, fungi and other micro-organisms such as archaea that likely play critical roles in our health. Additionally, it is not possible to know if many of the market driven therapeutics such as probiotics are beneficial or harmful. Some early work on probiotics shows that in about half of the people taking probiotics, the probiotics pass straight through the body into the stool.
An exciting and well-designed Stanford study showed that a diet high in fermented foods favors a more diverse microbiome and lower levels of inflammation in the body. If replicated, this and other microbiome interventions such fecal transplants could offer novel future treatments for human health.
Bradford Rabin MD (bradfordrabinmd.com) is a concierge medicine physician for San Francisco Bay patients including Palo Alto, Menlo Park, Los Altos, Woodside, Hillsborough, and Portola Valley.
1. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis
2. Gut microbiome diversity is associated with sleep physiology in humans
3. Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration
4. Interaction between drugs and the gut microbiome
5. Gut-microbiota-targeted diets modulate human immune status
6. What Makes a Microbiome Healthy?
7. Age-associated gut microbiota impairs hippocampus-dependent memory in a vagus-dependent manner
8. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice
9. Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression