The Gut-Brain Axis & Systems Biology

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Neurogastroenterology, a subspecialty of gastroenterology that overlaps with neurology, encompasses the study of the brain, the gut, and their interactions. It is a particularly fascinating area of research with a rapidly evolving knowledge base. Specifically, neurogastroenterology focuses on the functions, malfunctions, and the malformations of the sympathetic, parasympathetic, and enteric divisions of the digestive tract.

In 2017, for the first time in humans, UCLA researchers established an association between gut microbiota and brain regions involved in processing sensory information.1 The study showed that differences in gut microbial composition correlate with regional brain volumes in patients with irritable bowel syndrome (IBS). It also shed light on the connections between childhood trauma, brain development, and gut microbiome composition.

The study found a trend for a greater history of childhood emotional trauma in IBS, and the study’s authors speculated that “brain driven disturbances of the gut microbial environment in early life may have a long lasting effect on gut microbial composition persisting throughout life, which in turn may lead to further changes in brain structure/function.”1 The correlation of microbial taxa with early adverse life events, and with distinct brain structural changes, suggests a possible role of gut microbes and their metabolites in the development and shaping of the gut-microbiota-brain axis early in life.1

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The gut-brain axis is the bidirectional communication between the gut and the brain, which occurs through multiple pathways that include hormonal, neural, and immune mediators.2 Interestingly, the signals along this axis can originate in the gut, the brain, or both, with the objective of maintaining normal gut function and appropriate behavior.2 However, scientists struggle to uncover whether brain and behavioral alterations precede gut dysfunction and dysbiosis or vice-versa.2

“It’s important to recognize that many times when there’s inflammation in other areas of the body, it could be coming from the digestive system,” says IFM educator Elizabeth Boham, MD, MS, RD, IFMCP. “All of the systems of the body are intertwined.”

In the following video, Dr. Boham talks about how she uses the functional medicine DIGIN mnemonic to assess and heal her patient’s digestive and system-wide disorders:

(Video Time: 2 minutes). Dr. Boham is board certified in family medicine and is a certified IFM practitioner who is on the faculty of The Institute for Functional Medicine. She has developed a functional nutrition course that educates physicians and other health professionals worldwide.

Animal and human studies suggest that alterations in the gut-brain axis may be involved in the pathogenesis of an array of disorders, including IBS,3 dementia,4 Alzheimer’s and Parkinson’s diseases,5,6 and disorders of mood and affect such as major depressive disorder, chronic pain,7 and schizophrenia.8 However, there continues to be controversy over the magnitude of these effects, as well as the pathways and molecular mechanisms within the gut-brain axis that may be responsible for these alterations.7,9,10 While it has been well established that probiotics have therapeutic effects on many GI disorders, their ability to improve mood and cognitive function continues to be studied.11

Probiotics, Mood Disorders, and Dementia

Clinical studies have shown a connection between supplementation with probiotics containing specific species and strains of bacteria and the regulation of the body’s response to stress as well as with the exacerbation of depressive and anxiety symptoms in humans.12 A 2015 study found that fermented foods that contain probiotics may have a protective effect against social anxiety for those at higher genetic risk, as indexed by trait neuroticism.13 Researchers have also studied the potential of manipulating the GI microbiota to alleviate depressive symptoms.11,14,15 A 2020 systematic review and meta-analysis found that compared to placebo, probiotic consumption significantly reduced depressive symptoms among patients with depression (standardized mean difference (SMD) = -0.87; 95% CI: -1.66, 10.99; p = 0.03); however, no significant difference in symptoms was noted for patients with schizophrenia, stress, and anxiety.15

Conclusions from a 2021 systematic review based on both animal and clinical trials supports previous research results that indicate probiotics help to restore homeostasis of gut microbiota and to treat inflammation and oxidative stress related to Alzheimer’s disease.16 While researchers report that the exact mechanisms are not completely clear, their conclusions strongly suggest that probiotics help alleviate the progression of the disease.16

Future research in the area of neurogastroenterology will continue to cast light onto the gut-brain relationship and the therapeutic effects of probiotics on psychiatric and cognitive symptoms. A better understanding of the gut microbiota and their metabolites could revolutionize the possibility of therapies like diet and eating habits for many diseases.17,18

Learn More About gut Dysfunction and Chronic Conditions

Related Articles

The Microbiome, Stress Hormones, and Gut Function

IBS Development: Primary Causes & Triggers

Neurodegenerative Disease: Improving Outcomes Through Nutrition


  1. Labus JS, Hollister EB, Jacobs J, et al. Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome. Microbiome. 2017;5(1):49. doi:10.1186/s40168-017-0260-z
  2. De Palma G, Collins SM, Bercik P, Verdu EF. The microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both? J Physiol. 2014;592(14):2989-2997. doi:10.1113/jphysiol.2014.273995
  3. Lee CY, Abizaid A. The gut-brain-axis as a target to treat stress-induced obesity. Front Endocrinol. 2014;5:117. doi:10.3389/fendo.2014.00117
  4. Saji N, Niida S, Murotani K, et al. Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan. Sci Rep. 2019;9(1):1008. doi:10.1038/s41598-018-38218-7
  5. Matheoud D, Cannon T, Voisin A, et al. Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1-/- mice. Nature. 2019;571(7766):565-569. doi:10.1038/s41586-019-1405-y
  6. Barrio C, Arias-Sánchez S, Martín-Monzón I. The gut microbiota-brain axis, psychobiotics and its influence on brain and behaviour: a systematic review. Psychoneuroendocrinology. 2022;137:105640. doi:10.1016/j.psyneuen.2021.105640
  7. Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015;125(3):926-938. doi:10.1172/JCI76304
  8. Xu R, Wu B, Liang J, et al. Altered gut microbiota and mucosal immunity in patients with schizophrenia. Brain Behav Immun. 2020;85:120-127. doi:10.1016/j.bbi.2019.06.039
  9. Arneth BM. Gut-brain axis biochemical signalling from the gastrointestinal tract to the central nervous system: gut dysbiosis and altered brain function. Postgrad Med J. 2018;94(1114):446-452. doi:10.1136/postgradmedj-2017-135424
  10.  Simpson CA, Diaz-Arteche C, Eliby D, Schwartz OS, Simmons JG, Cowan CSM. The gut microbiota in anxiety and depression – a systematic review. Clin Psychol Rev. 2021;83:101943. doi:10.1016/j.cpr.2020.101943
  11.  Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann Gen Psychiatry. 2017;16:14. doi:10.1186/s12991-017-0138-2
  12.  Herman A. Probiotics supplementation in prophylaxis and treatment of depressive and anxiety disorders – a review of current research. Psychiatr Pol. 2019;53(2):459-473. doi:10.12740/PP/92392
  13.  Hilimire MR, DeVylder JE, Forestell CA. Fermented foods, neuroticism, and social anxiety: an interaction model. Psychiatry Res. 2015;228(2):203-208. doi:10.1016/j.psychres.2015.04.023
  14.  McKean J, Naug H, Nikbakht E, Amiet B, Colson N. Probiotics and subclinical psychological symptoms in healthy participants: a systematic review and meta-analysis. J Altern Complement Med. 2017;23(4):249-258. doi:10.1089/acm.2016.0023
  15.  Zagórska A, Marcinkowska M, Jamrozik M, Wisniowska B, Pasko P. From probiotics to psychobiotics – the gut-brain axis in psychiatric disorders. Benef Microbes. 2020;11(8):717-732. doi:10.3920/BM2020.0063
  16.  Naomi R, Embong H, Othman F, Ghazi HF, Maruthey N, Bahari H. Probiotics for Alzheimer’s disease: a systematic review. Nutrients. 2021;14(1):20. doi:10.3390/nu14010020
  17.  Novotný M, Klimova B, Valis M. Microbiome and cognitive impairment: can any diets influence learning processes in a positive way? Front Aging Neurosci. 2019;11:170. doi:10.3389/fnagi.2019.00170
  18.  Tran SM, Mohajeri MH. The role of gut bacterial metabolites in brain development, aging and disease. Nutrients. 2021;13(3):732. doi:10.3390/nu13030732

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