Microbiome and Probiotics: Gut bacteria can affect your mental health?

Microbiome and Probiotics: Gut bacteria can affect your mental health?

While trying to find research articles within the realm of Psychosynthesis (“Psychosynthesis”, n.d.), I have been looking at the collective unconscious.

While researching this, I stumbled on some interesting information on how your gut bacteria microbiome may affect your mental health and the other way round.

Gut microbiome and the Collective Unconscious

What I stumbled upon was an article by Dinan, et al. (2015) which states that:

  • Gut microbes are part of the unconscious system influencing behaviour.
  • Microbes majorly impact on cognitive function and fundamental behaviour patterns.
  • Disorganisation of the gut microbiota can negatively impact on mental health.
  • Psychobiotics are probiotics with a potential mental health benefit.

Gut bacteria communication with the brain

They also talk about bidirectional communication between gut microbes and the brain occurring via a number of routes including the vagus nerve (cranial nerve X), the hypothalamic-pituitary-adrenal axis (HPA) and cytokines produced by the immune system.

Bacteria also have the capacity to generate many neurotransmitters and neuromodulators. For example, certain Lactobacillus and Bifidobacterium species produce gamma-aminobutyric acid (GABA); EscherichiaBacillus and Saccharomyces spp. produce norepinephrine (NE); Candida, Streptococcus, Escherichia and Enterococcus spp. produce 5HT; Bacillus produces dopamine (DA); and Lactobacillus produces acetylcholine (Lyte, 2011Lyte, 2013Wikoff et al., 2009). Some probiotics can modulate the concentrations of opioid and cannabinoid receptors in the gut epithelium (Rousseaux et al., 2007). However, how this local effect occurs or translates to the anti-nociceptive effects seen in animal models of visceral pain is currently unclear.

(Dinan, et al. 2015)

Three questions arise from this

  1. Can poor mental health affect the bidirectional communication between gut microbes and the brain?
  2. Can consuming products containing probiotics be used to help with mental health problems?
  3. If so, can consuming products containing probiotics when well cause mental health problems?

The following is a talk by Olivia Gordon (2017) of SciShow, transcribed and slightly rephrased by me for ease of reading. I have also added a few additional bits of referenced information. References provided in the talk page is also provided below.

The Gut Microbiome

There are trillions of microbes inside you right now. Living out their lives. They are a whole community called your microbiome. Scientists are starting to realise that your microbiome plays a big role in your overall health. That is changing the way doctors treat all kinds of conditions, from prescribing antibiotics to managing IBS.

It’s obvious, in a way, that the microbes living in your gut can play a role in your dietary needs, and gastrointestinal health. They are a big part of the digestive process. What might not be so obvious is that the microbiome in your gut can also affect your brain.

The Gut-Brain Connection

Biologists used to think that was impossible due to the blood brain barrier and the intestinal barrier. But now, they are finding out that they were wrong. They are finding all kinds of connections from how stress affects the microbiome in your intestines, to how the microbiome affects behaviour.

Your guts might have such a big influence in your brain that funding agencies are pouring millions of pounds into understanding what researchers are calling the Brain-Gut-Microbiome Axis, or sometimes the Microbiome-Gut-Brain Axis. The microbiome can sometimes be referred to as the gut microbiota, so it can also be called the Brian-Gut-Microbiota Axis or the Microbiota-Gut-Brain Axis.

By understanding more about this connection, scientists are hoping to better understand human mental health, and maybe even develop some new therapies along the way.

Microbiota vs microbiome

There are subtle differences between what a microbiome is and the microbiota, and to understand those differences, you can read about the differences at the FIOS Genomics website (FIOS Genomics, n.d.).

We have known for a long time that your gut and your brain are closely connected in some ways. For instance, researchers have been studying the enteric nervous system (ENS), and its dynamic relationship with the central nervous system (CNS). We have also known that stress could affect digestion. Who hasn’t experienced tummy troubles during a stressful week?

The ENS and CNS

The ENS is a massive web spread over your entire digestive tract made up of more than 500 million neurons that control your guts. This second brain as it is sometimes called, is pretty much self sufficient, and can take care of most of its jobs by itself. But it is connected to the CNS through your vagus nerve, which is an information superhighway between your gut and your brain.

the vagus nerve at the level of the intestines.  the microbiome affects communication with the brain
Image source: Wikimedia Commons

Despite this connection, for a while, scientists assumed that the microbes in your gut could not affect your brain, because of the blood brain barrier. Your brain’s blood vessels are structured so they are packed very closer together. This keeps the brain’s immune system separate from the rest of the body.

The blood brain barrier

The blood brain barrier is very important. This is because although an infection in your toe or on your skin are not usually like threatening, brain infections tend to be pretty deadly. So your brain is structured to keep infections out. It is hard for almost anything, including microbes, to get through the barrier, except in serious injury or illness. So neuroscientists thought we can ignore the microbiome.

Answer to Question 1: Can poor mental health affect the bidirectional communication between gut microbes and the brain?

Even though there is cross talk between your ENS and your brain, researchers assumed that microbes did not play into it. But recent breakthroughs are challenging that assumption, and changing our understanding of how the blood brain barrier works, because the microbiome can affect your brain in some pretty big ways.

Stress affects your microbiome

Early research starting in the 1970s (Tannock & Savage, 1974) showed that stress could affect the kind of microbes found in the guts of mice. One group found that stressing mice by depriving them of food or water, caused them to have more coliform bacteria like E.coli, and less of another form of bacteria called lactobacilli in their intestines.

Another group found that the stress of dealing with an aggressive cage mate led to changes in amounts of other kinds of bacteria. They found increased numbers of Bacteriodes and Clostridium, along with decreased numbers of Coprococcus, Pseudobutyrivibrio and Dorea.

But even though it was clear that stress could affect the kinds of microbes in the intestines, it wasn’t clear if that was a 2 way relationship.

Could Gut microbes be affecting psychological stress levels?

The first big break on this question came when some scientists from Kyushu University, Japan (Sudo, et al. 2004), discovered that exposure to certain kinds of microbes had dramatic effects on brain chemical levels.

For this study, the scientists used germ free mice. These were mice delivered by C section and immediately put into super clean cages, so they were barely exposed to microbes at all. They also made comparisons with specific pathogen free mice. These were mice only exposed to a known set of microbes.

The germ free mice got a lot more stressed when they were restrained, so it was something about the bacteria in the specific pathogen free mice that was helping them with their stress levels.

The team found that the germ free mice had less of a protein called Brain-derived neurotrophic factor (BDNF). BDNF is important for learning, memory, and higher order thinking. The germ free mice had less of it in the brain regions that determine how an animal reacts to stress.

How are BDNF levels affected?

It’s not clear how exactly, that microbes could be affecting BDNF levels. We are still pretty sure they cannot cross the blood brain barrier under normal circumstances. But something about the presence of bacteria in the gut, seems to have a body wide effect that leads directly to changes in brain chemistry.

The results of that study kicked off more research projects to better understand the relationship between the microbiome and the brain. This is mostly using germ free mice.

Some research from the early 2010s found that while the germ free mice were more affected by certain kinds of acute stress, like restraint, they were less anxious about other kinds of stress, like being placed in a new environment. So it seems that the relationship between microbes and stress is complex.

Mice without a microbiome are not always more sensitive to stress.

Other studies have looked into what happens when you colonise germ free mice with bacteria. Does their behaviour change? How do the bacteria affect certain stress related genes in the brain?

In a study from 2011 (Bercik, et al. 2011), one group of scientists found that exposing germ free mice to the microbiomes of other mice could influence their behaviour. A shy germ free mouse might do more exploring if it was implanted with microbes from a more adventurous mouse. The behavioural changes also corresponded to an increase in that BDNF protein so the microbiome transplant had a direct effect on the brain chemistry.

So it is clear the connection is there. The microbiome does affect the brain. Now, all kinds of scientists are examining the Brain-Gut-Microbiome Axis. They have started to learn a lot about how your microbial balance can affect the balance of specific chemical messengers in your body and brain.

The microbes in your gut produce a lot of different molecules. And somehow, despite the blood brain barrier, these chemicals affect your brain.


This is a critical messenger in your brain, and it is especially well known for influencing mood. That’s why a lot of drugs prescribed for depression and anxiety affect the levels of serotonin signalling in the brain.

But, it turns out that the majority of your body’s serotonin isn’t made in your brain. Up to 80% of it is made in your gut, and the microbes living there can affect the amount of serotonin is produced. So changes in the numbers of microbes which produce serotonin could have big effects on overall levels of serotonin in your body, and could also affect your brain.

What about the immune system?

Even when they are not producing important neurotransmitters, microbes can trigger responses from the immune system. The immune response can also have a big impact on the brain.

The microbiome can affect the production of cytokines (proteins produced by the immune system. Some of those cytokines such as interleukin 6 are known to influence stress.

Researchers have also discovered that microbes can release molecules that affect the behaviour of the blood brain barrier. The affects can make it more or less permeable to outside molecules, affecting what is allowed in and out of the brain.

But even though scientists can pick out little bits of the puzzle, they still cannot see the whole picture yet. The germ free mice studies have been important and informative, but it is hard to translate the results to humans because mice are not humans.

There is no situation where a human will be totally microbe free, but these studies do show that the microbiome has an effect on the brain. And they are still useful because they give researchers total control over what kinds of bacteria the mice are or are not exposed to.

There is even a new study (Werbner et al. 2019) which found differences in mouse bacterial compositions when exposed to social stress, with the biggest changes in two particular types: bilophila and dehalobacterium. Both types have been linked with autoimmune disorders in humans, notably multiple sclerosis.

The researchers followed with a genetic analysis and found genes linked to “violent traits” switched on, which, according to the study, increase growth, movement, and signalling between bacteria and host. In other words, the bacteria appear to have turned into destructive pathogens with enhanced ability to travel through the body and infect tissue.

Further analysis of the lymph nodes of the stressed mice confirmed that connection, finding high levels of pathogenic bacteria and a density of “self-reactive effector t-cells” (immune system cells) that are characteristic of autoimmune disorders.

When taken together, these results suggest that a percentage of the stressed gut bacteria in the mice became pathogenic and infected their tissue, leading to the immune system attacking the body.

Answer to Question 2 and 3: Can consuming products containing probiotics be used to help with mental health problems? If so, can consuming products containing probiotics when well cause mental health problems?

There is not a lot of research that is very clear on the relationship between the gut and the brain in humans. These discoveries are so new that nobody has been able to do any large scale studies in humans yet. But along with prebiotics (fibre supplements designed to feed good bacteria), small studies have tried treating volunteers with probiotics, deliberately introducing new microbes in to there guts, and the microbes and fibre affected the subjects mood and cognition.

So there might be a relationship between your microbiome and your mental health. But the studies have not been able to look closely enough at what exactly the prebiotics and probiotics are doing to the microbes in the gut, or how that may be translating in to changes in mood.

What does this mean?

Researchers will be getting more into the nitty-gritty of these relationships and trying to work out whether these discoveries can translate into medical treatments.

Other scientists are trying to work out how to humanize the mouse microbiome, making the mouse microbiome more human like. They are doing this by taking faecal matter from sick and healthy human patients and inserting them into mice to study the effects.

That kind of experiment can let researcher pick apart how differences in the microbiomes connects with changes in mental health. They can also get right into the brains of mice in ways they can’t with human patients, using dissected tissues to look directly at the structures of brain cells and how they connect.

Can we tailor our microbiome for maximum benefit?

Some researchers are also trying to figure out how specific kinds of microbes are affecting our brains and how we can tailor our microbiomes to maximize the health benefits.

Others are starting to ask questions about how other things that affect our microbiomes like antibiotics could be affecting our mental health and cognition.

So there is still a lot we don’t know about how our microbiome can affect our brain. But there are a lot of new studies in the works and scientists and doctors are hoping that as our knowledge of how our Brain-Gut-Microbiome Axis grows, so will our ability to tweak it and hopefully improve some lives along the way.

Further reading provided in the talk page.

Bailey, M. T., Dowd, S. E., Galley, J. D., Hufnagle, A. R., Allen, R. G., & Lyte, M. (2011). Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain, behavior, and immunity25(3), 397–407. doi: 10.1016/j.bbi.2010.10.023 Free PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039072/pdf/nihms253984.pdf

Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., … & Verdu, E. F. (2011). The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology141(2), 599-609. doi: 10.1053/j.gastro.2011.04.052 Free PDF: https://www.gastrojournal.org/article/S0016-5085(11)00607-X/pdf

Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology28(2), 203–209. pmcid: PMC4367209 Free PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/pdf/AnnGastroenterol-28-203.pdf

Furness J.B., Callaghan B.P., Rivera L.R., Cho HJ. (2014) The Enteric Nervous System and Gastrointestinal Innervation: Integrated Local and Central Control. In: Lyte M., Cryan J. (eds) Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease. Advances in Experimental Medicine and Biology, vol 817. New York, NY: Springer. doi: 10.1007/978-1-4939-0897-4_3

Human Microbiome Project Consortium (2012). Structure, function and diversity of the healthy human microbiome. Nature486(7402), 207–214. doi: 10.1038/nature11234 Free PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564958/pdf/nihms378076.pdf

Mayer, E. A., Knight, R., Mazmanian, S. K., Cryan, J. F., & Tillisch, K. (2014). Gut microbes and the brain: paradigm shift in neuroscience. The Journal of neuroscience : the official journal of the Society for Neuroscience34(46), 15490–15496. doi: 10.1523/JNEUROSCI.3299-14.2014 Free PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228144/pdf/zns15490.pdf

Mayer, E. A., Tillisch, K., & Gupta, A. (2015). Gut/brain axis and the microbiota. The Journal of clinical investigation125(3), 926–938. doi: 10.1172/JCI76304 Free PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362231/pdf/JCI76304.pdf

Reardon, S. (2014). Gut–brain link grabs neuroscientists. Nature News515(7526), 175. doi: 10.1038/515175a Free PDF: https://www.nature.com/news/polopoly_fs/1.16316!/menu/main/topColumns/topLeftColumn/pdf/515175a.pdf

Smith, P. A. (2015). The tantalizing links between gut microbes and the brain. Nature News526(7573), 312. doi: 10.1038/526312a Free PDF: https://www.nature.com/news/polopoly_fs/1.18557!/menu/main/topColumns/topLeftColumn/pdf/526312a%20corrected.pdf

Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X. N., … Koga, Y. (2004). Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. The Journal of physiology558(Pt 1), 263–275. doi: 10.1113/jphysiol.2004.063388 Free PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664925/pdf/tjp0558-0263.pdf

Tannock, G. W., & Savage, D. C. (1974). Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract. Infection and immunity9(3), 591–598. pmcid: PMC414848 Free PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC414848/pdf/iai00243-0111.pdf


Dinan, T. G., Stilling, R. M., Stanton, C., & Cryan, J. F. (2015). Collective unconscious: how gut microbes shape human behavior. Journal of psychiatric research, 63, 1-9. doi: 10.1016/j.jpsychires.2015.02.021 Free PDF: https://www.sciencedirect.com/science/article/pii/S0022395615000655/pdfft?md5=ff7cd05c4c73610666af148419fccba6&pid=1-s2.0-S0022395615000655-main.pdf

FIOS Genomics. (n.d.). Microbiome vs Microbiota. Retrieved from https://www.fiosgenomics.com/microbiome-vs-microbiota/

Gordon, O. (2017). Your Microbiome and Your Brain. SciShow. Retrieved from https://youtu.be/2ycHwcV9MvM

Lyte, M. (2011). Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. Bioessays, 33(8), 574-581. doi: 10.1002/bies.201100024 Free PDF: Insane Medicine

Lyte, M. (2013). Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior. PLoS pathogens, 9(11), e1003726. doi: 10.1371/journal.ppat.1003726 Free PDF: https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003726&type=printable

Psychosynthesis (n.d.). Retrieved from https://en.wikipedia.org/wiki/Psychosynthesis

Rousseaux, C., Thuru, X., Gelot, A., Barnich, N., Neut, C., Dubuquoy, L., … & Ouwehand, A. (2007). Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nature medicine, 13(1), 35. doi: 10.1038/nm1521 Free PDF: http://www.academia.edu/download/42302843/Lactobacillus_acidophilus_modulates_inte20160207-14055-3116ew.pdf

Werbner, M., Barsheshet, Y., Werbner, N., Zigdon, M., Averbuch, I., Ziv, O., … & Koren, O. (2019). Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells. *MSystems, 4*(4), e00292-18. doi: 10.1128/mSystems.00292-18 (Open Access)

Wikoff, W. R., Anfora, A. T., Liu, J., Schultz, P. G., Lesley, S. A., Peters, E. C., & Siuzdak, G. (2009). Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proceedings of the national academy of sciences, 106(10), 3698-3703. doi: 10.1073/pnas.0812874106 Free PDF: https://www.pnas.org/content/pnas/106/10/3698.full.pdf

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