A Gut Feeling

gut-microbiotaYou may have heard this potentially horrifying fact before: there are more microbes in your gut than there are cells in your body. That’s over 100 trillion bacteria, all primarily within your colon.[1] If we were to consider every microbial being on your body right now- your roughly 37 trillion human cells would be outnumbered 10 to 1.[2] That’s great (read: terrifying) and all, but why does it matter?

I had the pleasure of interviewing Dr. Justin Sonnenburg, a researcher at Stanford University (The Sonnenburg Lab) and coauthor of “The Good Gut,” who sums it up like this: “You have these microbes associated with your body that are absolutely fundamental to your health, and if these microbes aren’t taken care of, your health is going to take a hit because of it.”[1]

What is the Gut Microbiota?

The gut microbiota refers to the collection of all the microbes inside the human gut. It has a huge impact on human health- and digestive health is only the most obvious of the ways it affects the body. The human gut microbiota influences weight gain, immune function, and the brain, just to name a few. So that brings up a question: what is it about these gut microbes that allows them to affect so much of human physiology?

In the womb, humans are sterile- they have absolutely no microbial life anywhere on them. As soon as, and even while they’re born, however, babies’ bodies are colonized by a huge diversity of microbial life. A baby born naturally is exposed to his mother’s vaginal microbiota, bacteria already tested and used by the mother’s body. Babies born by Cesarean-section develop gut microbiota that are more similar to the skin microbiota of doctors, friends, and family, and are more likely to have an unhealthy microbiota even years later.[3] [Click here for the report on this study]

The Gut Microbiota and Weight Gain

In a UK study of over 11,000 children, researchers found that babies who had received antibiotics before 6 months of age, on average weighed more than children of the same age who had not received antibiotics. Even more striking, this difference in weight was still present up to three years of age, more than two years after the antibiotic treatment that separated the two groups.[Here] This effect, where antibiotic use is followed by weight gain, has been shown in laboratory mice as well; even mice that ate and exercised exactly the same amount gained weight differently depending on antibiotic use.[Here] This is because the composition of the microbiota, the population of bacteria inside you, changes the way the body stores calories as fat. The microbiota of an obese person is radically different from that of a lean person. Studies have even shown that transplanting the microbiota  of an obese mouse into a lean mouse is enough to cause weight gain without changing the mouse’s lifestyle in any way.[3]

The microbiota is a complex system- while there are diseases in which one specific bacteria causes one specific disease, the effect of the microbiota on its host is primarily an ecological effect. It is how the thousands of bacterial species in the gut interact with surrounding human cells and with the environment that determines disease or health. This discovery has led to an entirely new way of thinking about bacteria as a complex community inside us and all around us rather than solely considering “good”  or “bad” bacteria.[1]

The Microbiota and the Immune System

Lately, it has become obvious that the microbiota intimately affects the immune system as well, arguably acting as a secondary immune system. This field of study is still very new, and scientists are discovering things we’d never imagined were possible. Scientists are only now realizing that the traditional militaristic image of the immune system as a personal army that wards off invaders doesn’t nearly convey the entirety of what it does. Some even think that the immune system should be renamed to better reflect the complexity of its role in the body. Most of the immune cells in your body are located in your digestive tract, in constant contact and communication with the bacteria there.[3] The microbiota is hugely important to the functioning of your immune system- not only to prevent food-borne illness, but even basic immune function, like warding off a flu virus, will be impaired if the microbiota is unhealthy. Furthermore, immune cells in the colon don’t always stay there- they can travel through the bloodstream to other locations in the body. This means that an immune cell can directly  interact with the gut microbiota one day, and be in the lung the next- using information it learned from bacteria in the colon to more effectively do its job elsewhere in the body.[1]

In the gut, the mucosal immune system needs to maintain the delicate balance between its pro-inflammatory and anti-inflammatory sides, preventing bacteria from breaching the intestinal wall without causing the wall to become excessively inflamed. This balance is dependent on the microbiota; overly aggressive bacteria can lead to an overaggressive immune system and inflammatory bowel disease (IBD). In 2011, researchers at California Institute of Technology found that changing the composition of the gut microbiota in mice with multiple sclerosis dramatically changed the speed at which the disease progressed, showing very vividly how the gut microbiota could affect autoimmunity, and a disease that seemed wholly unrelated to digestion.[Here] Autoimmune diseases, cancer, IBD, and repressed immunity have all become more prevalent in the increasingly westernized world. “It appears that the Western lifestyle has…disrupted the seesaw, jeopardizing the delicate balancing act that keeps both the pro- and anti-inflammatory  branches of our immune system peacefully coexisting with our microbes.”[3]

The Microbiota Today

Increased C section births, use of antibiotics, and even the sterility of the environment most newborns in the western world experience have contributed to a less robust microbiota, and therefore a less healthy immune system. Laboratory mice that have no gut microbiota have fewer resident immune cells in their gut, making them more susceptible to infection if exposed to germs present in the outside world. Because much of immune system development occurs very early in life, even if these mice are later inoculated with a gut microbiota, their immune systems never adjust to function optimally. Furthermore, allergies are more prevalent in the western world than in less developed countries. This paired with the fact that children who grow up with dogs, have multiple siblings, are raised on farms or are otherwise more exposed to bacteria are less likely to develop allergies or asthma make a strong case for the hygiene hypothesis, which credits the reduced exposure to infectious agents and even nonpathogenic bacteria with the increased prevalence of allergies.[3] [Read the papers here and here]

Sanitation has tremendously decreased deaths from infectious diseases and saved lives, so the answer isn’t to abandon advances in cleanliness and sterilization procedures entirely, but to step away from the overuse that is the practice today. Proportionally, very few microbes that humans come in contact with every day cause disease. Exposure to a diverse range of bacteria, even those that are not pathogenic, strengthen the immune system, causing it to respond in small ways by identifying each new bacteria as threatening or nonthreatening, and therefore keeping the immune system “on its toes.” The rise of hand sanitizer, antibacterial soap, antibacterial-infused kitchen utensils, even hand washing in excess, and urbanization that separates us from interacting with soil and nature in general have weakened our immune systems, while overuse of antibiotics have created strains of dangerous, untreatable superbugs- bacteria who don’t respond to treatment.[3]

 The Microbiota and the Brain

The effect of the gut microbiota doesn’t stop there. New research has shown that the health of our microbiota is inarguably and intimately tied to the health of our brains as well. Stress turns on the fight or flight response, activating our sympathetic nervous system, causing a host of physiological effects including faster heart rate, higher blood pressure, and slowed digestion. This decrease of the gut transit time of food consumed radically changes the environment that the microbiota is exposed to in the colon, immediately changing which bacteria flourish, and which do not. The enteric nervous system is the branch of the nervous system that regulates our digestion. It is so large and complex, it can function on its own, without interference from the brain. However, it is connected to the central nervous system by hundreds of millions of  neurons, and is in engaged in constant, two-way conversation with our brains.[3]

Serotonin is a neurotransmitter responsible in large part for feelings of happiness, which is also thought to affect mood, social behavior, appetite, digestion, sleep, memory and sexual desire. It is manufactured in the brain and the intestines, but 80-90% of it is found in the gastrointestinal tract, with our friends, the microbiota.[4] The vast majority of drugs prescribed in the US to treat disorders like anxiety and depression do so by affecting serotonin levels. At UCLA in 2013, researchers did a study in which participants were split into three groups: one group ate a yogurt with four known bacterial species, one group ate a placebo yogurt that was bacteria free, and a third consumed nothing outside of their normal habits. The results were incredible: in just one month, women in the first group showed differences in brain activity when compared to women in the other two groups. The changes were seen in areas across the brain, including the prefrontal, frontal and temporal cortexes and the periaqueductal gray area, which are involved in processing sensory input and emotion, and are important in anxiety disorders, pain perception and even irritable bowel syndrome.[3] [Here]

Though discoveries made in trials with animals can’t be directly applied to humans, several recent studies done with lab mice hold enormous promise for advances to come in the field. Researchers have found that mice without a microbiota take more risks, and have difficulty in creating long term memories.[Here and here]  When two groups of mice have their microbiotas swapped, their behavior changes. In this experiment, anxious and brave mice, as measured by the length of time it took them to climb down a precarious platform, had their microbiotas swapped. Both types of mice showed radical behavior change;. their times differed by more than a minute compared to their original. The brave group took much longer, and the anxious group much less time to complete the same task as before, showing that the microbiota can affect our thoughts and behaviors.[Here]

Many researchers also believe that the microbiota may be the key to Autism Spectrum Disorders. Many people who have ASD also experience gastrointestinal problems, and when researchers delved deeper, they found that ASD patients often had very homogenous microbiotas. In a study done at Caltech, researchers introduced a bacterial species named Bacteroides fragilis, which helps repair intestinal ‘leakiness’ that is often characteristic to the colons of people with ASD to mice that displayed ASD-like symptoms. When they did so, the mice displayed decreased severity of symptoms: decreased anxiety and repetitive behaviors, and improved communication.[3] [Here]

More and more studies are being done on psychobiotics, which aim to ameliorate psychiatric symptoms by normalizing the amounts of various chemicals and neurotransmitters in the body and increasing the health and diversity of the gut microbiota.  While all of this research is still very new, it shows great promise. It is very possible that we will be better able to treat and prevent these types of diseases very near in the future by harnessing the power of  the microbiota.[3]

The Microbiota and You

As stated in The Good Gut, “Unlike the human genome, which is largely fixed before birth, the microbiome can be altered throughout life by way of strategic choices that are within our control.”[3] One of the biggest ways to affect the microbiota is by changing our diets. Most of the microbiota in our gut live at the end of it, in the large intestine. When we eat something like cake, which is primarily sugar, fat, and simple carbs, most of the nutrients are absorbed in the stomach and the small intestine, so by the time the food reaches the microbiota, there isn’t much left. People whose diets are low in dietary fiber and high in simple carbs and sugars will have a starving microbiota. The malnourished microbiota then begins eating the mucosal lining of the intestines, a tremendously important barrier for preventing infection. Foods like carrots or broccoli on the other hand, are full of dietary fiber, which makes it all the way down to the colon, and feeds the microbiota, keeping it healthy. Changing your diet will immediately impact the microbiota- as soon as increased amounts of fiber reach the colon, the bacteria will change their behavior, switching from consuming the mucosal lining we need, to helping us break down and make use of dietary fiber and producing many important byproducts. However, a sudden change to a healthier diet won’t increase the diversity of the microbiota, which is often left decimated after microbiota famine caused by a low fiber diet.[1] In order to increase the number of species present, its often a good idea to consume foods that contain bacteria, like yogurts and other fermented foods, in addition to increasing daily intake of dietary fiber and consuming more plant material.[1,3]

At the end of my interview with Dr. Sonnenburg, I asked him whether his research had changed his lifestyle and habits in any way. He was fervent that it had.

“Completely yes- I’ve totally changed my diet, my lifestyle, and how I raise my kids. In fact, it was the motivation to write this book [The Good Gut] with my wife- she’s a researcher here as well. We felt like all  the microbiota researchers were all doing the same things in terms of modifying their diet and lifestyle, and nobody else was. It’s very clear that people in this field are distilling out the same take home messages. Those messages are: eat way more dietary fiber and plant material, less red meat. Limit antibiotics to when they’re absolutely essential. Most investigators eat fermented food now, yogurt, kimchi, sauerkraut. And then for raising kids: try to avoid C sections if you can, and try to breastfeed your baby. These are the simple rules that we’ve implemented and that other people in the field have implemented as well.”[1]

Interested? Check Out These Links!

  1. The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-Term Health
  2. The Sonnenburg Lab
  3. Youtube/podcast with both Dr. Sonnenburgs
  4. The Human Microbiome Project
  5. Gut Microbiota World Watch

 

References:

  1. Sonnenburg, Justin. “The Gut Microbiota.” Personal interview. 09 Nov. 2015.
  2. Chutkan, R. (2015, February 12). Why The Microbiome Is The Future Of Medicine. Lecture presented at Live Dirty, Eat Clean! Retrieved from https://www.youtube.com/watch?v=pDBI9txA-W0
  3. Sonnenburg, J., & Sonnenburg, E. (2015). The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-Term Health. New York, New York: Penguin Press.
  4. McIntosh, J. Reviewed by Webberley, H. (n.d.). Retrieved December 9, 2015, fromhttp://www.medicalnewstoday.com/articles/232248.php

 

Image Credit: Earle, Kristen. Sonnenburg Lab [Spatial Organization of the Gut Microbiota]. Retrieved January 4, 2015 from http://sonnenburglab.stanford.edu

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