I’ve spent last week embedded in research about the microbiome–a fancy term that describes the microbes that inhabit the entire human body, although this conference focused primarily on microbes that live in our gut. Fungi and viruses barely received a nod of acknowledgement, but that work will have to wait. We know even less about them.
Over three days a small crowd of about 200 post doc types filled the conference room, hailing from a wide range of disciplines. From the start everyone characterized the state of microbiome research as “preliminary”. That means we have a few ideas, but don’t know nearly enough. The research presented pointed to what can be characterized as “The post pastuerian era.” We need to start working with the bugs instead of trying to eradicate them.
A SURVEY OF CURRENT UNDERSTANDING AND KEY INSIGHTS
In June of 2013 several journals printed the initial findings from the The Human Microbiome Project. Since then, scientists have learned a great deal in a very short period of time. Throughout the microbiome conference I repeatedly sat back and tried to absorb it all. I’ll summarize my key take away points here.
1. Ninety percent of the cells in the human body are actually microbial cells, with microbes contributing over 99% of “our” genes. We host a wide range of microbes. Between individuals microbe diversity is highly variable, changes over time, and responds acutely to our environment.
2. Pregnancy, a vaginal delivery and breastfeeding offer the fetus and newborn their first and most critical exposure to healthy microbes. But a mother can also transfer a compromised microbiome. (HINT: We need more ways to help women cultivate a healthy microbiome before they even get pregnant)
3. Microbes are inherently competitive with other microbes and the host (that’s us). The competitive selection mostly favors the fast evolving microbe. (And not us)
4. Microbial insults drive inflammation, as well as a compromised immune system and increased incidence of disease. Improved resilience with a healthier microbiome will improve our health.
5. Changes in our diet lead to short term changes in our microbiome, but these changes are reversible. TRANSLATION: Microbes adapt to what you eat on a meal to meal basis. This is sobering news for those who want to treat an unhealthy gut with probiotic supplements but continue to eat poorly. Food matters.
6. Studying the microbiome is fraught with challenges for the scientist. Every aspect of the research model needs to be carefully managed and detailed as finding are published. Contamination of the environment is possible at every stage of the process. Microbes live everywhere and on everything, from research subjects to the materials used and anyone involved with the research. Replication will be necessarily to validate any findings from a singular trial.
Specific Concerns: Medicine
1. Use of antibiotics drives antibiotic resistance, providing humans with first hand exposure of evolution in real time. In the past decades of cavalier antibiotic use and abuse, bacteria achieves resistance to a new antibiotic in as little as 4-5 years.
2. Today one notorious resistant bacterium, C Difficile, kills 14,000 patients a year. Incredulously, in one study fecal transplants allowed for a significant increase in microbial diversity and led to a 90% cure rate.
3. Many medical practitioners prescribe far fewer antibiotics, but change is slow. Currently some doctors suggest only prescribing antibiotics for life threatening conditions.
4. Antibiotics typically eradicate the least resistance microbes. After a course of antibiotics, a smaller diversity of more resistant microbes are likely to prevail. Americans tend to harbor lower diversity. Obese subjects are also known to harbor less diversity. It is unknown if we can re-establish a healthier and more diverse microbiome after antibiotic use.
5. Researchers linked antibiotic resistance to weight gain, regain after weight loss, and resistance to losing weight. Antibiotic resistance is also linked to insulin resistance, glucose intolerance, and the metabolic syndrome. At this point it is unclear whether the impact is cause or consequence. Potential mechanisms of action for microbes include variations in:
- Energy harvest — the relative efficiency of metabolizing energy from the food we eat. Mouse models currently blow up the energy balance equation and any notion that a calorie is a calorie.
- Systems regulating food intake — microbes likely influence gut peptides such as ghelin, leptin, GLP-1 and PYY that conduct signals of hunger and satiety
- Inflammation – could be characterized as a state of microbial overgrowth or imbalance
- Partitioning of stored calories – microbes may be involved in determining where energy is stored, especially conditions linked to insulin resistance such as fatty liver disease or NASH
- Energy expenditure–microbial balance may determine how many calories are actually used for any one activity. Researchers note a significant change in brown fat and resting energy expenditure with changes in the microbiome. As many of us have suspected, the efficiency of our metabolism is highly variable.
- Satiety/addiction–our microbiota composition is known to impact the endocannabinoid system which operates in a part of the brain known as the pleasure center.
6. One particular microbe known as Akkermansia muciniphila is known to control gut barrier function, increase insulin sensitivity, while decreasing inflammation, fat mass and plasma cholesterol in mice. All the mice were given the same calories, there was no evidence of fat malabsorption, but the microbe was linked to a much improved level of fat oxidation.
7. Imbalanced gut microbiota precedes type I diabetes in animal models. Antibiotic exposure increases risk of type II diabetes. Researchers aim to find out if dysbiosis predicts diabetes in humans.
8. Microbes exert a different impact on women compared to men. Microbial colonization influences testosterone synthesis in females, but even more in males.
9. Both prebiotics (nutrients that feed healthy bacteria) and probiotics (the healthy bacteria) are shown to improve a wide range of metabolic functions in test animals and humans.
10. Gastric bypass works best to help patients lose weight due to changes in hormonal and metabolic signaling. Changes in the microbiome are thought to be critical to these changes. In animal studies weight loss is greater in gastric bypass animals despite eating more than the controls.
Specific Concerns: Agriculture and Food
1. Sub-therapeutic doses of antibiotics in young mice leads to adult onset obesity. Researchers wonder about the practice of sub-therapeutic doses of antibiotics in food animals and the humans who eat them.
2. Agriculture uses 70-80 percent of all antibiotics, mostly as growth promoters in animal feed. The FDA has requested voluntary reduction and some change is happening, but not nearly fast enough. Dr. Martin Blazer chaired this conference. In his book, Missing Microbes, he wonders in print if we are fattening children much like CAFOs fatten livestock.
3. Food processing introduces food components that are likely to influence the microbiome. One research pointed out potential problems with the emulsifiers polysorbate 80 and carboxymethylcellulose (CMC). In mice, intake over time linked to a thinning of gut mucosa and greater inflammation. Mice exposed to the emulsifiers exhibited 2x the incidence of colitis. Both additives are currently approved by FDA as “Generally Regarded as Safe” (GRAS)
I was most heartened by the last three hours of the conference. A free flowing exchange of ideas amongst the scientists offered a rare fly-on-the-wall experience for someone like myself. I am struck by the enormity of the task ahead.
1. Two thirds of the genes of the microbiome are uncharacterized. One researcher stated that “the reference data is a mess.” They have more work to do and we have much more to learn.
2. Many different bacteria exert a similar impact on metabolic functions. Scientists recognize that in the future, they will need to focus on function more than taxonomy.
3. In conditions such as Irritable Bowel Disease (IBD) and Crohn’s disease, metabolic pathways may be more disturbed than organisms. In this way, the metabolites of microbes also impact the balance of pro-inflammation versus anti-inflammation.
4. Researchers focus on a “high fat diet” because they are trying to provoke a diabetic state. They recognize the need to address a range of dietary patterns. In addition, the mix of carbohydrate, protein and fat may be only the beginning. Non calorie nutrients and additives in food matter, too.
Researchers recognize that everyone is looking for answers, and some are not waiting for the science. The sobering truth is that we are working with a highly complex microbiome and highly complex host. We will also need to explore the impact of a highly complex environment. For example, American farmers use increasingly greater amounts of glyphosate to control weeds and aid in harvesting crops. Glyphosate interrupts a key metabolic pathway in plants and microbes. About 50% of US cropland is treated with glyphosate, and greater residues are found in the food supply every year. Shockingly not one scientist or doctor I talked to had heard of glyphosate, and I ended up spelling it for a few who wanted to look at it more closely.
Despite the relative lack of information, I’d rather not gamble with our current adulterated food supply. I’ll continue to to mostly eat whole foods with minimal exposure to conventional pesticides and processing that could compromise my health and the diversity of microbes in my gut. I shop for organic produce and animals raised without antibiotics, both at home and when I can on vacation. I have resolved that it’s time we learn to live with the bugs rather than merely trying to eradicate them. Sure buying food is more expensive, but the cost of health care is far greater. I am willing to spend more to work with my body– and the many microbes I currently host. What about you?