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.
Works Cited:
Browning, K.N. and Mendelowitz, D., 2003. Musings on the wanderer: what’s new in our understanding of vago-vagal reflexes?: II. Integration of afferent signaling from the viscera by the nodose ganglia. American Journal of Physiology. Gastrointestinal and Liver Physiology, [online] 284(1), pp.G8–14. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/12488231>.
Cho, I. and Blaser, M.J., 2012. The human microbiome: at the interface of health and disease. Nature Reviews Genetics. [online] Available at: <http://www.nature.com/doifinder/10.1038/nrg3182> [Accessed 21 Oct. 2014].
Cohen, S. and Janicki-Deverts, D., 2012. Who’s Stressed? Distributions of Psychological Stress in the United States in Probability Samples from 1983, 2006, and 20091: PSYCHOLOGICAL STRESS IN THE U.S. Journal of Applied Social Psychology, [online] 42(6), pp.1320–1334. Available at: <http://doi.wiley.com/10.1111/j.1559-1816.2012.00900.x> [Accessed 22 Oct. 2014].
Cryan, J.F. and O’Mahony, S.M., 2011. The microbiome-gut-brain axis: from bowel to behavior: From bowel to behavior. Neurogastroenterology & Motility, [online] 23(3), pp.187–192. Available at: <http://doi.wiley.com/10.1111/j.1365-2982.2010.01664.x> [Accessed 22 Oct. 2014].
Forsythe, P., Bienenstock, J. and Kunze, W.A., 2014. Vagal pathways for microbiome-brain-gut axis communication. Advances in Experimental Medicine and Biology, [online] 817, pp.115–133. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/24997031>.
Kunze, W.A. et al., 2009. Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. Journal of Cellular and Molecular Medicine, [online] 13(8B), pp.2261–2270. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/19210574>.
Lyte, M., 2013. Microbial Endocrinology in the Microbiome-Gut-Brain Axis: How Bacterial Production and Utilization of Neurochemicals Influence Behavior. PLoS Pathogens, [online] 9(11), p.e1003726. Available at: <http://dx.plos.org/10.1371/journal.ppat.1003726> [Accessed 21 Oct. 2014].
Mao, Y.-K. et al., 2013. Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons. Nature Communications, [online] 4, p.1465. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/23403566>.
Peterson, G., Kumar, A., Gart, E. and Narayanan, S., 2011. Catecholamines increase conjugative gene transfer between enteric bacteria. Microbial Pathogenesis, [online] 51(1-2), pp.1–8. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/21419838>.
Roshchina, V. V., 2010. Evolutionary Considerations of Neurotransmitters in Microbial, Plant, and Animal Cells. In: M. Lyte and P.P.E. Freestone, eds. [online] New York, NY: Springer New York, pp.17–52. Available at: <http://link.springer.com/10.1007/978-1-4419-5576-0_2> [Accessed 22 Oct. 2014].
Wu, R.Y. et al., 2013. Spatiotemporal maps reveal regional differences in the effects on gut motility for Lactobacillus reuteri and rhamnosus strains. Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society, [online] 25(3), pp.e205–214. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/23316914>.
Hi all,
This post relates to my future IP project, and the Year 2 Neuro project. I was introduced to the topic of microbiome-brain interactions by a co-worker in my lab. Thanks for taking the time to read my post. Please let me know if you have an comments.
Jonathan
Hi Jonathan,
Great blog post; it was both enjoyable and informative. I have a few comments for you to make your post better:
1) You should change all your citations to Harvard Style. It appears right now you are using some sort of other citation style that involves superscripts.
2) There is an extra space between the last 2 paragraphs.
3) It may be beneficial to insert an image into your post. This will provide readers with a different way of looking at your post and it will add more ‘flavour’ to it.
4) I am thoroughly impressed by the number of sources you have cited, all of which appear to be journal articles. This is astounding and I applaude you for such efforts.
Overall your blog post is wonderful and I am excited to read the final draft.
Shawn
Hey Joho,
This post was really well written. I just have a few suggestions:
– “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.” I’m just a little bit confused here, do you mean the efferent vagus nerve? because the vagus nerve is innervating the gut?
– “The rising incidences of multidrug resistant bacteria are on the rise, and may be correlated of overall population stress levels, which are also rising.” You say rise a lot here 😛
Happy editing!
Leah
Hi Jonathan,
Nice immuno post!
You should switch your reference style to Harvard, I assume you are using Mendeley so just change that.
If you were so inclined, you could summarize some of the data for the treatment of rats with Bacteroides fragillis into a table showing the effects of treatment.
My favourite part was the section on neuroendocrine hormones, and I like the connection at the end to multidrug resistance- that was a really cool point. Try to reword that last sentence to avoid the word “rise” twice in that sentence. I quite enjoyed this post! Thanks Joho keep it up.
– Julia M
Ditto on what Julia says, change your references.
The second and third paragraphs could really be shortened to two sentences. One saying that the Vargas nerve is the main nerve which interacts with the stomach and a second sentence on the study showing that microbes have an effect on the nerve.
The sentence “are all exactly the same in structure” needs to be explained (the chemist in me demands an explanation of what part of the structure remains common).
Again the sentence “The rising incidences of multidrug resistant bacteria are on the rise, and may be correlated of overall population stress levels, which are also rising” needs to be addressed. Which population stress levels are you referring to the bacteria’s stress level or society in general.
The conclusion has a lot of fluff one thing that you can add is the relationship between the gut biome and autism. This relationship is one of the biggest impact that your topic has at large.
Hello Jonathan,
Gut microflora/fauna is really important to human health, but it’s not well studied, as you point out. Maybe you’ll unexpectedly discover something huge (but probably tiny because they’re bacteria) during your IP.
I have some comments about your writing:
-“not much is known about microbiome-host interactions, and remains a keen topic of research” is awkwardly phrased. Perhaps you should remove the comma and add “it remain a…”
-“Numbering in 100 trillion cells, the human microbiome is comprised of 10 times” the correct idiom is “numbering in the 100s of trillions of cell…”, and the correct use of “comprise” should be “the human microbiome comprises 10 times…”. Alternatively, it can be “… microbiome is composed of 10 times…”
-In your first paragraph, the semicolon should actually be a colon: the phrase after your semicolon is not an independent clause
-“rats were fed with the beneficial bacteria” remove the word “with”
-“Surprisingly, the majority of neuroendocrine hormones found in all walks of life, including plants, animals, and microbes, are all exactly the same in structure” using “majority” and “all exactly the same” seems slightly contradictory
-“The rising incidences of multidrug resistant bacteria are on the rise, and may be” remove this comma, it’s unneeded (you have several other unneeded commas throughout; take a look at them)
I hope these points were helpful.
James Lai