Probiotics and Mental Health

Question

While trying to find research articles within the realm of Psychosynthesis, I have been looking at the "collective unconscious"

^{Image Source: Wikipedia Commons - (CC BY-SA 3.0)}

1. Lower Unconscious
2. Middle Unconscious
3. Higher Unconscious
4. Field of Consciousness
5. Conscious Self or "I"
6. Higher Self
7. Collective Unconscious

Conducting a Google Scholar search for "collective unconscious" I stumbled on an article by Dinan, et al. (2015) which states:

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

they also talk about bidirectional communication between gut microbes and the brain occuring 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); Escherichia, Bacillus and Saccharomyces spp. produce norepinephrine (NE); Candida, Streptococcus, Escherichia and Enterococcus spp. produce 5HT; Bacillus produces dopamine (DA); and Lactobacillus produces acetylcholine (Lyte, 2011, Lyte, 2013, Wikoff 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.

My question is can poor mental health affect the bidirectional communication between gut microbes and the brain, and can consuming products containing probiotics be used to help with mental health problems? If so, will consuming products containing probiotics when well cause mental health problems?

References

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

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: Semantic Scholar

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

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

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

Answer 1

The following, and more, is available at my blog article Microbiome and Probiotics: Gut bacteria can affect your mental health?

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 enteric nervous system (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.

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.

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.

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 suppliments 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

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 immunity, 25(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. Gastroenterology, 141(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 gastroenterology, 28(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. Nature, 486(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 Neuroscience, 34(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 investigation, 125(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 News, 515(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 News, 526(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

References

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 physiology, 558(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 immunity, 9(3), 591–598. pmcid: PMC414848 Free PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC414848/pdf/iai00243-0111.pdf