The human microbiome is perhaps one of the most subtle and unfamiliar aspects of modern medicine. Though some bacteria have been shown to be beneficial to human health, not much is known about microbiome-host interactions. It remains a keen topic of research. Numbering in 100 trillion cells, the human microbiome is comprised of 10 times more cells than those from their host. The microbiome is found throughout the body: on the skin, in the eyes, mouth, stomach, intestines and even the lungs (Cho and Blaser, 2012). The interactions of the microbiome are thought to have subtle, albeit vital, effects on these organs, but perhaps the most peculiar interface is the one between our gut microbiome and our brain.
The 10th cranial nerve, or the vagus nerve, innervates the pharynx, larynx, heart and intestines, and is the principal afferent nerve for the abdominal cavity. The vagus nerve also transmits inputs from the muscle and mucosal layers of the gut, and has the highest receptor density in the area. Along with the high receptor density, the afferent vagus nerve is connected to a diverse range of chemoreceptors and mechanoreceptors, allowing the gut to interpret and distinguish a variety of signals. The relationship between the gut and the vagus nerve is the main method in which the microbiome interacts with the brain (Forsythe, Bienenstock and Kunze, 2014; Cryan and O’Mahony, 2011; Browning and Mendelowitz, 2003).
In one experiment, rats were fed the beneficial bacteria Bacteroides fragilis for 9 days and found an increased excitability of the primary afferent neurons in the intestine and a shortening of the post action potential refractory period, suggesting that the neurons were becoming more sensitive to the changes in the intestinal lumen (Kunze et al., 2009; Mao et al., 2013). In a follow-up experiment, the primary afferent neurons of germ-free animals were studied in an attempt to understand the effects of microbiome absence. These neurons showed a reduced level of excitability, and a refractory period longer than any seen in healthy animals (Forsythe, Bienenstock and Kunze, 2014). These findings suggest that the gut microbiome has an essential effect on the normal function of primary afferent nerves. These nerves are responsible for relaying information to the brain, which in turn regulates gastrointestinal motility (Wu et al., 2013). In this way, the communication between microbiome and brain becomes a key factor in digestion and intestinal health.
Another important interaction between the brain and the microbiome is through neuroendocrine hormones. Surprisingly, the majority of neuroendocrine hormones found in all walks of life, including plants, animals, and microbes, are identical in chemical structure (Roshchina, 2010). The field of microbial endocrinology examines the neuroendocrine-bacterial interactions that are key to understanding the subtle changes in health (Lyte, 2013). One study found that the microbiome responds pathogenically in response to periods of host stress. During stress responses, the catecholamines adrenaline and norepinephrine are released, which are also cues for bacterial growth, motility and virulence. Catecholamines have also been shown to enhance horizontal gene transfer efficiency, which can result in multidrug resistant bacteria (Peterson, Kumar, Gart and Narayanan, 2011). The growing incidences of multidrug resistant bacteria may be correlated of overall population stress levels, which are also rising (Cohen and Janicki-Deverts, 2012).
The gut microbiome-brain interaction is perhaps one of the strangest relationships known, and is a booming area of research. The intricate functions of the microbiome are not fully known, though it is known that they play a vital role in human health, and their absence has been implicated with some diseases. Understanding the complex relationship between microbiome itself, and with the host will play an important role in our understanding of disease and health maintenance in the future, and is at the frontier of medical research.
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