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, finding a trend for a greater history of childhood emotional trauma in patients with IBS.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 Scientists continue to investigate the patterns and mechanisms involved with gut-brain communications that occur during either health and disease in humans.

“If there are imbalances in the digestive system, if there is increased intestinal permeability, if there is dysbiosis, if there is improper digestion and absorption,” explains IFM educator Elizabeth Boham, MD, MS, RD, IFMCP, “that can trigger immune activation in the body and systemic inflammation.”

In the following video, Dr. Boham discusses the functional medicine DIGIN mnemonic that helps clinicians assess the digestive system health of their patients.

(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 inflammatory bowel disease (IBD),³ dementia,⁴ Alzheimer’s and Parkinson’s diseases,^5,6 and disorders of mood and affect such as major depressive disorder,⁷ chronic pain,⁸ and schizophrenia.⁹ 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.^10,11 While it has been well established that probiotics have therapeutic effects on many GI disorders,^12-14 their ability to improve mood and cognitive function continues to be studied.^15,16

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.^17,18 A 2020 meta-analysis of seven randomized controlled trials (n=1,146 total healthy adult participants) found that probiotic supplementation reduced subjective stress levels among healthy adults compared to placebo and may help relieve stress-related anxiety and depression levels in this population.¹⁸ Another 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.¹⁹

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.²⁰ While researchers report that the exact mechanisms are not completely clear, their conclusions strongly suggest that probiotics help alleviate the progression of the disease.²⁰

Future neurogastroenterology research 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.^21,22

The Microbiome, Stress Hormones, and Gut Function

IBS Development: Primary Causes & Triggers

Neurodegenerative Disease: Improving Outcomes Through Nutrition

References

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:1186/s40168-017-0260-z
Margolis KG, Cryan JF, Mayer EA. The microbiota-gut-brain axis: from motility to mood. Gastroenterology. 2021;160(5):1486-1501. doi:1053/j.gastro.2020.10.066
Fairbrass KM, Lovatt J, Barberio B, Yuan Y, Gracie DJ, Ford AC. Bidirectional brain-gut axis effects influence mood and prognosis in IBD: a systematic review and meta-analysis. Gut. 2022;71(9):1773-1780. doi:1136/gutjnl-2021-325985
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:1038/s41598-018-38218-7
Claudino Dos Santos JC, Lima MPP, Brito GAC, Viana GSB. Role of enteric glia and microbiota-gut-brain axis in Parkinson disease pathogenesis. Ageing Res Rev. 2023;84:101812. doi:1016/j.arr.2022.101812
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:1016/j.psyneuen.2021.105640
Bhatt S, Kanoujia J, Mohana Lakshmi S, et al. Role of brain-gut-microbiota axis in depression: emerging therapeutic avenues. CNS Neurol Disord Drug Targets. 2023;22(2):276-288. doi:2174/1871527321666220329140804
Magni G, Riboldi B, Ceruti S. Modulation of glial cell functions by the gut-brain axis: a role in neurodegenerative disorders and pain transmission. Cells. 2023;12(12):1612. doi:3390/cells12121612
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:1016/j.bbi.2019.06.039
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:1136/postgradmedj-2017-135424
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:1016/j.cpr.2020.101943
Zhang XF, Guan XX, Tang YJ, et al. Clinical effects and gut microbiota changes of using probiotics, prebiotics or synbiotics in inflammatory bowel disease: a systematic review and meta-analysis [published correction appears in Eur J Nutr. 2021;60(5):2877]. Eur J Nutr. 2021;60(5):2855-2875. doi:1007/s00394-021-02503-5
Zhang T, Zhang C, Zhang J, Sun F, Duan L. Efficacy of probiotics for irritable bowel syndrome: a systematic review and network meta-analysis. Front Cell Infect Microbiol. 2022;12:859967. doi:3389/fcimb.2022.859967
Zheng Y, Zhang Z, Tang P, et al. Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials. Front Immunol. 2023;14:1143548. doi:3389/fimmu.2023.1143548
Sikorska M, Antosik-Wójcinska AZ, Dominiak M. Probiotics as a tool for regulating molecular mechanisms in depression: a systematic review and meta-analysis of randomized clinical trials. Int J Mol Sci. 2023;24(4):3081. doi:3390/ijms24043081
Liu C, Guo X, Chang X. Intestinal flora balance therapy based on probiotic support improves cognitive function and symptoms in patients with Alzheimer’s disease: a systematic review and meta-analysis. Biomed Res Int. 2022;2022:4806163. doi:1155/2022/4806163
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:12740/PP/92392
Zhang N, Zhang Y, Li M, et al. Efficacy of probiotics on stress in healthy volunteers: a systematic review and meta-analysis based on randomized controlled trials. Brain Behav. 2020;10(9):e01699. doi:1002/brb3.1699
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:3920/BM2020.0063
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:3390/nu14010020
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:3389/fnagi.2019.00170
Tran SM, Mohajeri MH. The role of gut bacterial metabolites in brain development, aging and disease. Nutrients. 2021;13(3):732. doi:3390/nu13030732

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