Gut Dysbiosis and the Microbiota Throughout Your Life:
This week we are diving deeper into your gut microbiota throughout your life and gut dysbiosis which we touched on last week.
Your microbiota is as unique to you as your fingerprints. This is why it’s unlikely that any single probiotic or psychobiotic will work for everyone. You will need to experiment to see what works best for you. There are 100 trillion bacteria in your gut, composed of at least 500 species. The bulk of them, some 98 percent, come from about 40 species divided into just four big groups (phyla). The two main groups are Lactobacillus and Bifidobacteria. Gut microbes produce all manner of chemicals to talk with each other and to your gut; that information is relayed to your brain primarily via the vagus nerve, which is a long wandering nerve from the brain to all your bodily organs. The problem with this communication is that it has very few words. It’s mostly “okay, okay, okay, hungry, hungry, full, okay, okay…”. Here’s an example of how that works. Some microbes, especially our friendly Bifido species, produce butyrate, which feeds and heals the lining of your gut. Butyrate can make its way to the brain, where it can induce a good mood, dampen inflammation, or encourage the production of a brain-growth hormone. All these changes can improve your mood and even help you to think better. Sugar cravings can be seen as a consequence of a dysbiotic gut. That is likely related to the sugar cravings of people in mental hospitals. Sugar cravings have also been seen in people who are stressed. These are pathogens, but the same principles seem to apply to commensal bacteria as well. If they don’t get what they want, they can make a fuss. When that happens, you may not know it directly, but they have ways of making you uncomfortable until you give them what they want. It’s that funky feeling that makes you suddenly crave a candy bar or other snack. You may not know why, but you know there is a bonbon-size hole in your gut, and it quickly becomes your job to fill it. If your gut is healthy, there will be a cosmopolitan bustle of microbes with no one species dominating. That means that no one species can exert too much control. A dysbiotic gut, on the other hand, has less diversity. Let’s look at a dysbiotic gut through life starting with mom and baby. A dysbiotic gut may not respond properly to the estrogen, which can lead to problems down the road for both mother and child. Meanwhile, at this stage of pregnancy, your mother’s gut microbiota is changing to accommodate feeding you. Remarkably, these changes look a lot like metabolic syndrome, a kind of prediabetes, inducing weight gain and insulin resistance. Between the first and third trimester, the number of bacterial species drops and those that remain seem to favor putting on fat. This means that there must be some kind of mechanism that prods the gut microbiota toward extracting extra energy from food to take care of you. The same mechanism, triggered at the wrong time, could lead to obesity, gut dysbiosis, and even type 2 diabetes. You are swathed in this bacterial blanket before you ever poke your head out of the womb. Unless you get violently ill or end up on an antibiotic regimen in the first days of your existence, your body will form a memory of this first bacterial initiation that will likely last for the rest of your life. This bacterial appetizer is there, among other reasons, to teach your immune system what to expect. If you were born by cesarean, you missed a lot of that messy stuff. Instead, you were whisked away to a nursery where you picked up a bacterial population unique to your nurse’s skin and your hospital. Some studies have shown that children delivered by C-section may lack important Bacteroides species for up to the first 18 months of life, making them more likely to suffer from asthma and allergies. New studies suggest that babies born by C-section react differently to stress, and may even be more susceptible to depression and anxiety—all hypothetically correlated to gut and microbiota health. Not all studies are so downbeat, though: New research has shown that at around six weeks, the microbiota of most of these children has normalized, with some of that due to breast-feeding. Jumping quick to why having bacteria is good and that includes a balance of both the good and the bad. If you grew up or choose to now live in a germ free environment you may have some differences in your brain. Studies have also shown that a germ-free mouse may have an unusual hippocampus, a seahorse-shaped part of the brain that is involved with both memory and emotion, and amygdala. We noted some dramatic changes in nerve cells, including different kinds and shapes of neurons as well as the growth of more new nerve cells than in normal mice. Somehow, the microbiota is controlling the growth of important memory and anxiety centers of the brain. We have also demonstrated that extra myelin is formed in the brains of germ-free mice. We found that myelination—especially in a region of the brain known as the prefrontal cortex —is regulated by the microbiome. The prefrontal cortex is an important area for top-down regulation of the stress response and is involved with depression and schizophrenia. We found that these changes could be reversed by providing the mice with a conventional microbiota after weaning, suggesting that the microbiota is a potential target for myelin-based psychiatric disorders. This observation, which came to be called the hygiene hypothesis, implies that cleanliness actually has a negative influence on normal development, and it has had a big impact on how people look at bacteria. Rather than being pathogenic or at best marginally useful, a certain set of bacteria may actually be essential for the proper development of your body’s defenses. It is the job of these microbes to train your immune system, and without them, your system stays naive and prone to overreaction.
Remember bacteria are important! Back to mom and baby let’s look at breastmilk. Breastmilk is both a prebiotic and probiotic drink—a combination of microbes and the food microbes want—a sort of homemade kefir. These prebiotics not only feed the starter microbiota, they also reduce the release of the stress hormone cortisol, keeping you happy and content. The first milk, produced right after delivery, is called colostrum and is packed with hundreds of species of bacteria. It is also full of maternal white blood cells and antibodies to establish a newborn’s foundational immune system—kind of an immune system transplant, designed to provide instant protection for your defenseless body. For such an innocuous-looking substance, milk packs an astounding immunological punch. The milk is filled with regulatory cells called T-regs. They are important players in the baroque world of immunity. As a baby, your thymus is highly active while you build up your unique collection of antibodies and T-regs. As you get older, your thymus shrivels, and you might find it harder to fight off pathogens. That can lead to chronic inflammation and depression as you age. After around six months of breast-feeding, the bacteria in your mother’s milk start to change. Instead of bacteria that are expert at digesting milk sugars, the new milk microbiota starts to look a lot like your mother’s own oral bacteria. This transformation helps prepare you for solid food, because a lot of the work of digestion starts in the mouth. Mucus in the gut comes in multiple formulations. First a network of sugary strands stuck tight to the enterocytes provides an excellent physical barrier against microbes. On top of that is a second, less dense mucus layer full of a microbial buffet of sugars. Embedded in this second mucus layer is your most important defense against pathogens: other bacteria. During the early years of your life, your immune system needs to be educated to leave these protective bacteria alone. If your immune system kills your guardian bacteria, pathogens can directly attack your gut. They can eat holes in your gut lining, letting bacteria into your bloodstream and provoking a systemic immune response. Although the basic framework of your microbiota is set by age two, it is still a dynamic situation. As you grow, there will still be changes, and there is an overall drift away from Bifido species. Teenage diets, typically laughable, lead to a rash of gut problems. And stress affects the teenage brain and microbiota alike. There’s good news and bad: You can make a difference, because this may be the last time in your life that you can make durable changes to your microbiota. But if a bad set of microbes gets established, you may have to fight for the rest of your life to keep the upper hand. It’s never too late: A good diet can keep your gut happy, increase your health span, and improve your mood, all at the same time.
