Gut Microbiome and Neuropsychiatry - A Systems Biology Perspective

If our #diets are important because of the nutrients we intake and the fuel and building blocks they provide us, they are also of significant importance because of the other biological entities that live on and in us —they also appreciate what we eat.?

The Human Microbiota-Gut-Brain Axis

The human #gut #microbiome represents a densely populated #microbial niche, with growing evidence pointing toward its role in regulating behavior and brain function (Flint, Scott, Louis, & Duncan, 2012). This bidirectional communication, known as the microbiota-gut-brain axis, operates through various pathways, including the vagus nerve, the immune system, neuroendocrine pathways, and bacteria-derived metabolites (Cryan & Dinan, 2012). Systems biology, which offers an integrative approach to understanding the interplay between the gut microbiome and neuropsychiatry, can help identify patient-specific factors that contribute to our understanding of their relationship.

Gut microbiota influences multiple hormonal signaling pathways, such as metabolism, fertility, and the stress response in cognition. For instance, short-chain fatty acids produced by gut bacteria affect energy balance (Flint et al., 2012). Additionally, the gut microbiota plays a role in nutrient absorption (Nicholson et al., 2012). Fertility is also impacted by the gut microbiome, as it can influence hormonal balance (Baker, Al-Nakkash, & Herbst-Kralovetz, 2017) and reproductive health (Koedooder et al., 2019). Furthermore, the gut microbiome influences the hypothalamic-pituitary-adrenal (HPA) axis, thus playing a role in stress-related psychiatric disorders (Kelly et al., 2016).

Inflammation

#Inflammation and #proinflammatorycytokines play a significant role in the interplay between the gut microbiome and #neuropsychiatry . General inflammation and inflammatory mediators can affect brain function (Dantzer et al., 2008), leading to alterations in mood and cognition (Miller & Raison, 2016). Proinflammatory cytokines produced by gut bacteria (Erny et al., 2015) have implications for neuropsychiatric disorders (Rooks & Garrett, 2016). For example, cytokines can modulate neurotransmission, influencing the development and progression of psychiatric conditions (Miller & Raison, 2016).

Cytokines can modulate neurotransmission, influencing the development and progression of psychiatric conditions

If you have ever read anything I’ve posted recently, you will know that I continue to advocate for precision medicine approaches, which take into account an individual's specific clinical-genetic-biological characteristics, can help provide screening solutions, deploy time-sensitive detection/diagnosis, and then tailor treatment strategies for many neurological and psychiatric diseases. These diseases often involve complex, multifactorial etiologies, and a one-size-fits-all approach may not be effective in addressing the unique needs of each patient (Sarkar et al., 2016).

Diet Composition & Nutrition

#Diet composition and nutritional status have repeatedly been shown to be critical modifiable factors in regulating gut microbiota (David et al., 2014). Therefore, nutritional interventions may play a vital role in maintaining brain health. Probiotics and prebiotics, for example, have demonstrated the potential in modulating the gut-brain axis and improving neuropsychiatric conditions (Sarkar et al., 2016). Moreover, specific dietary patterns can also impact the gut-brain axis and mental health (Jacka et al., 2017).

Interventions & Psychobiotics

Dietary interventions, which can significantly impact gut microbiota composition, play a crucial role in modulating the gut-brain axis and mental health (David et al., 2014). For instance, a randomized controlled trial found that improvements in diet could help alleviate symptoms of major depression (Jacka et al., 2017). Adopting specific dietary patterns rich in prebiotics, probiotics, and anti-inflammatory compounds can promote a healthy gut microbiome and reduce inflammation, potentially improving neuropsychiatric conditions (Sandhu et al., 2017).

Psychobiotics, a subset of probiotics, are another promising strategy. These live microorganisms can manipulate the gut microbiota and modulate gut-brain signals, potentially improving mental health (Sarkar et al., 2016). Studies have demonstrated the potential of psychobiotics in alleviating stress-related psychiatric disorders and promoting overall mental well-being (Foster, Rinaman, & Cryan, 2017).

Leveraging the gut microbiome's influence on nervous system function requires targeted interventions, including dietary changes and psychobiotics, to maximize the potential benefits for individuals suffering from neuropsychiatric disorders. Further research should focus on the development of personalized approaches that take into account an individual's unique gut microbiome composition and specific neuropsychiatric condition.

A systems biology approach offers a promising avenue for furthering our understanding of neuropsychiatric diseases in general and the gut microbiome in the context of neuropsychiatric in particular. By elucidating the complex interplay between #gutmicrobiota , #neuroendocrine pathways, and the immune response, this approach can potentially facilitate the development of targeted therapies and precision medicine for neuropsychiatric conditions. Future research should focus on leveraging the potential of systems biology to identify patient-specific factors that contribute to the understanding of the gut microbiome and neuropsychiatry, with an emphasis on the interweaving nervous and immune systems in this context (Foster, Rinaman, & Cryan, 2017).

References:

[1] Flint, H. J., Scott, K. P., Louis, P., & Duncan, S. H. (2012). The role of the gut microbiota in nutrition and health. Nature Reviews Gastroenterology & Hepatology, 9(10), 577-589.

[2] Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., & Pettersson, S. (2012). Host-gut microbiota metabolic interactions. Science, 336(6086), 1262-1267.

[3] Baker, J. M., Al-Nakkash, L., & Herbst-Kralovetz, M. M. (2017). Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas, 103, 45-53.

[4] Koedooder, R., Singer, M., Schoenmakers, S., Savelkoul, P. H., Morré, S. A., de Jonge, J. D., & Poort, L. (2019). The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study. Human Reproduction, 34(6), 1042-1054.

[5] Cryan, J. F., & Dinan, T. G. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behavior. Nature Reviews Neuroscience, 13(10), 701-712.

[6] Kelly, J. R., Borre, Y., O'Brien, C., Patterson, E., El Aidy, S., Deane, J., ... & Dinan, T. G. (2016). Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. Journal of Psychiatric Research, 82, 109-118.

[7] Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nature Reviews Neuroscience, 9(1), 46-56.

[8] Miller, A. H., & Raison, C. L. (2016). The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nature Reviews Immunology, 16(1), 22-34.

[9] Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., ... & Prinz, M. (2015). Host microbiota constantly control maturation and function of microglia in the CNS. Nature Neuroscience, 18(7), 965-977.

[10] Rooks, M. G., & Garrett, W. S. (2016). Gut microbiota, metabolites and host immunity. Nature Reviews Immunology, 16(6), 341-352.

[11] David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., ... & Turnbaugh, P. J. (2014). Diet rapidly and reproducibly alters the human gut microbiome. Nature, 505(7484), 559-563.

[12] Sandhu, K. V., Sherwin, E., Schellekens, H., Stanton, C., Dinan, T. G., & Cryan, J. F. (2017). Feeding the microbiota-gut-brain axis: Diet, microbiome, and neuropsychiatry. Translational Research, 179, 223-244.

[13] Sarkar, A., Lehto, S. M., Harty, S., Dinan, T. G., Cryan, J. F., & Burnet, P. W. (2016). Psychobiotics and the manipulation of bacteria–gut–brain signals. Trends in Neurosciences, 39(11), 763-781.

[14] Jacka, F. N., O'Neil, A., Opie, R., Itsiopoulos, C., Cotton, S., Mohebbi, M., ... & Pasco, J. A. (2017). A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Medicine, 15(1), 1-13.

[15] Foster, J. A., Rinaman, L., & Cryan, J. F. (2017). Stress & the gut-brain axis: Regulation by the microbiome. Neurobiology of Stress, 7, 124-136.

Desiderio Pina, MD, MPH

TheMindAndBodyDoc-Physician/Neuroscientist —?@mindandbodydoc

I provide compassionate care for children (5 years & older), adolescents, adults & families struggling with nutritional, drug, & neuropsychiatric problems.

Teaching is always a privilege and I’ve had the privilege to teach at various medical schools (MD & DO), and residency programs (Psychiatry, Family Practice, and universities, and have done clinical and basic science research in the past. I’m currently on staff at a few hospitals and mostly care for patients via telemedicine.

I generally talk & write about things that catch my fancy in the news and from the recent medical literature.?

Including but not limited to: #wellness , #neurosciences , #neuropsychiatry #culturalpsychiatry #ethnobotony #mycology #mycologicalmedicine #digitalhealthcare , #healthcaremanagement , and #psychoneuroendocrineimmunology