Increasing BDNF (Brain-Derived Neurotropic Factor)

By Brian James Rose

Weighing a mass of three pounds, our brain is responsible for controlling all the major functions of the body. As the governing center of the body, the brain, instead of acting in isolation, works closely with other organs, responding to the needs and experiences of each of our biological systems. In a staggering statistical report, it has been revealed that our bodies are comprised of ten times more microbial cells than our own human eukaryotic cells. Increasing BDNF  These microbes are primarily formed of bacteria, viruses, and protozoa, and make up what’s called the commensal microbiome in the intestines. 

There are a hundred trillion of these bugs, reflecting over 10,000 unique species and contributing a hundred and fifty times more genes than our own human genomes. As per the estimated value, these microbes weigh around two to six pounds, which is up to twice the weight of an average adult human brain. Subsequent reports have shown that these commensal microbes have co-evolved to play fundamental roles in our normal brain developments and functions. We can further study the role of commensal microbes by raising mice as completely germ-free and recolonizing them with special microbes. 

We’re learning that commensal microbes regulate several complex behaviors like anxiety, learning, and memory, so studying this microbe brain interaction can lead to really important discoveries about how microbes can affect our brain health. In case you are wondering how in the world does a microbe affects your brain, there are many different mechanisms that can activate the vagus nerve such that the vagus nerve contacts the gut lining, extending all the way up to the brainstem. The bacterium involved in the process is called Lactobacillus rhamnosus. Curiously enough, in the task, it is found that mice that have been treated with this bug exhibit less depression-like symptoms, while this is not seen if the vagus nerve is completely severed. 

Another significant way by which microbes can affect the brain is by activation of the immune system, as about 80 percent of the body’s immune cells reside in the gut, and immune abnormalities contribute to several neurological disorders. This is a scientifically proven instance where the bacterium Bacteroidesfragilisprevents multiple sclerosis in mice. Having been treated with this bug, rodents show greater resilience to the disease, which depends primarily on the activity of a special subset of immune cells called regulatory t-cells. Blocking the activity of this immune cell will cut down the beneficial effects of these bugs. Another way bugs can affect the brain is by activating the gut endocrine system. Since gut endocrine cells are primary producers of neuropeptides and neurotransmitters, gut microbes themselves can also produce metabolites that could affect brain function. This pathway concerns the microbe-based treatment that researchers in the Patterson and Mazmanian lab have used to treat autism-like symptoms in mice. Treated with Bacteroidesfragilis, these rodents were able to overcome their core abnormalities, including communication deficit, which is the diagnostic symptom of autism.

The trillions of microbes, which live inside your body, form a complicated community, and in recent studies, bio-scientists are acknowledging the fact that the microbiome plays a pivotal role in your overall health. This revelation is influencing the medical approaches, from prescribing antibiotics to controlling IBS. The microbes in your gut have proven to regulate your dietary needs and gastrointestinal health. It was difficult to imagine that the microbiome in your gut can affect the brain, but studies are finding new connections every day, whether it is how stress affects the microbial buildup in your gut or how the microbiome affects the behavior of these organisms. With investors spending millions of dollars into understanding the microbiome-gut-brain access, scientists are hoping to discover more about human mental health, thereby facilitating the development of new therapies. 

The enteric nervous system has become the talking point in bioscience for quite some time, and the study of ENS’s dynamic relationship with the central nervous system is likely to open new doors in medical developments. Consisting of more than 500 million neurons, ENS is often considered as the second brain, controlling several important functions. It is connected to the central nervous system through the vagus nerve, which serves as a bridge between your gut and your brain. This gut-brain connection, scientists assume, is the primary reason why microbes in your belly affect your brain, and because of the blood-brain barrier, the brain’s blood vessels are designed in a clustered form, wherein they’re packed close to each other to keep the brain’s immunity system separate from the rest of your body. The Blood-brain barrier protects the brain from brain infections, which can have a life-threatening impact on your body. The blood-brain barrier is powerful enough to keep infections out, stopping the microbes from crossing the barrier except in cases of serious injuries. Although the role of the microbiome is controversial, there has been a lot of crosstalk between your ENS and your brain. The recent breakthroughs have challenged the previous microbial theories, altering our perspective on how the blood-brain barrier works.

Increasing BDNF

Increasing BDNF

The widespread research on the microbiome-brain connection made some striking revelations about how your microbial balance can affect the levels of specific chemical messengers in your body and brain. Conclusively, the microbes in your gut produce clusters of different molecules, and despite the blood-brain barrier, these chemicals tend to affect your brain. Serotonin, for instance, is a critical messenger in your brain, recognized for its influences on mood changes, so drugs prescribed for depression and anxiety affect serotonin signaling in the brain. Interestingly enough, the majority of your body’s serotonin isn’t produced in the brain since up to 80% of its content has its origin in the gut, and the microbes residing there can affect how much serotonin is produced, influencing overall levels of serotonin in your body. Serotonin could also affect the brain, and even if they don’t produce neurotransmitters, microbes can trigger responses from the immunity system. Since the immune response can have a substantial effect on the brain, the microbiome is assumed to affect the production of cytokines or the proteins formed by the immune system cells, while some of those proteins like one called interleukin 6 are known to influence stress levels. Researchers are of the opinion that microbes can release molecules that affect the behavior of the blood-brain barrier, making it somewhat permeable to outside molecules that can control what’s allowed in and out of the brain. Scientists are yet to assemble individual pieces of the puzzle, for they are clueless about the big picture. 

It was observed in research in the early 1970s that stress could determine the nature of microbes found in the guts of mice; depriving mice of food or water caused them to develop coliform bacteria like e-Coli and traces of other bacteria called lactobacilli in their intestine, while the stress of living with aggressive cage mate resulted in changes in the population. Although stress has proven to affect the kinds of microbes in the intestines, it could not be determined whether it is a two-way relationship, affecting psychological stress levels. The big breakthrough in 2004 provided some valuable insight into the matter, with scientists from Kyushu University in Japan discovering the dramatic impact on the brain chemical levels due to the exposure to certain forms of microbes. In this experiment, germ-free mice that were delivered by c-section were shifted into ultra-clean cages to prevent microbial contaminations. When contrasted with behavioral patterns of free mice, the germ-free mice got a lot more stressed out when they were restrained. It can, therefore, be concluded that the bacteria in the mice were helping them to keep their stress levels in control. Furthermore, the team discovered the brains of the germ-free mice had less BDNF-induced protein content. Since this protein is responsible for influencing learning, memory, critical thinking, and other faculties, the germ-free mice had difficulties dealing with their stress. It is, however, not clear how microbes could affect BDNF levels as crossing the blood-brain barrier seems implausible under normal circumstances. Many scientists associate infiltration with the body-wide effect of gut microbes on brain chemistry. 

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Some research from early 2010 observed that germ-free mice were prone to experience greater stress and restraint while they were less concerned about other forms of stress like being shifted to a new environment. Discernibly, the relationship between microbes and stress is complicated since germ-free mice aren’t always susceptible to stress. Studies have also examined what happens when you colonize germ-free mice with bacteria, besides finding out about behavioral changes or bacterial influences on certain stress-related genes in the brain. In research from 2011, a group of scientists concluded that exposure of germ-free mice to microbiomes of other mice could influence their behavior. It was found a timid germ-free mouse tends to explore more when it was implanted with the microbes from a more adventurous mouse which is whimsical, and the behavioral changes correspond to an increase in the BDNF protein. Since the connection between the microbiome transplant and brain chemistry is evident, the microbiome is looked upon as an important factor affecting the brain. This discovery has invigorated fresh interests in the investigation of the microbiome’s influence on the brain, and now all bioscientists are keen on how the microbiome got brain access. 

Increasing BDNF

Increasing BDNF

The germ-free mice studies have been highly informative, though it’s hard to replicate the procedures in human systems. Mice aren’t humans, and there’s no conclusive evidence that humans would be totally microbe-free. Although these studies do emphasize that the microbiome has a considerable effect on the brain, they’re not entirely valid as they give researchers total control over what kind of bacteria are exposed to the mice. Not all the find-outs shed light on the relationship between the gut in humans. Besides, these discoveries are relatively new, and no one’s been able to do any large-scale studies in humans. Only small studies have attempted treating volunteers with probiotics and deliberately introducing new microbes into their guts. Prebiotics, which are fiber supplements, are meant to feed good bacteria and microbes, while the fiber affected the subject’s mood and cognition. Subsequently, there might be an underlying relationship between your microbiome and your mental health. Though the studies haven’t been able to figure out what exactly the prebiotics and probiotics are doing to the microbes in the gut or how that might be initiating changes in MU.

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Looking at the research prospects, future researchers are likely to delve deeper into the nitty-gritty of these connections, figuring out whether the findings can be implemented into medical treatments. More and more scientists working on humanizing the mouse microbiome, taking transplants from both healthy and sick human patients, and introducing them into the mice to examine their effects. These experiments are enabling researchers to pick apart how differences in the microbiome can be connected with changes in mental health, understanding whether or not they can get right into the brains of mice in ways they can’t with human patients. Generally, researchers use dissected tissues to look directly at the structures of brain cells and how they connect, but some researchers are keen on finding out figure how specific kinds of microbes are affecting our brains and how we can tailor our microbial biomes to maximize the health benefits. Also, many researchers are starting to raise important questions about how other things can influence our microbial biomes. For instance, antibiotic treatments are believed to be affecting our mental health and cognition, so there’re plenty of things we don’t know about how our microbiomes affect our brain. Conveniently, there are several new studies that have emerged in this domain, and bioscientists are hoping that as our knowledge of the microbiome-brain association strengthens, we will be better disposed to tweak it, hopefully improving some lives along the way. 

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