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Neurogastroenterology & the Gut-Brain Axis

Close up of a woman's hands putting kimchi in a glass surrounded by herbs and gut health foods for balancing the gut-brain axis.

Explore the mechanisms underpinning gastrointestinal conditions at the upcoming GI Advanced Practice Module See full program details

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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. The bidirectional communication between the gut and the brain is known as the gut-brain axis and occurs through multiple pathways that include hormonal, neural, and immune mediators.1 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.1

Scientists continue to investigate the patterns and mechanisms involved with gut-brain communications that occur during either health or disease in humans. What functional medicine tools help clinicians assess the overall digestive health of their patients, and how does the latest gut-brain axis research help support individual treatment strategies for both gut and brain health?

The Gut-Brain Relationship: Chronic Disease Links

In 2017, for the first time in humans, UCLA researchers established an association between gut microbiota and brain regions involved in processing sensory information.2 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.2 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.2

Animal and human studies suggest that alterations in the gut-brain axis may be involved in the pathogenesis of an array of disorders, such as disorders of gut-brain interaction (DGBIs), formerly known as functional gastrointestinal disorders,3 inflammatory bowel disease (IBD),4 dementia,5 Alzheimer’s and Parkinson’s diseases,6,7 and disorders of mood and affect such as major depressive disorder,8 chronic pain,9 and schizophrenia.10 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.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

Clinical Applications: Functional Medicine Approach

Research suggests that the bidirectional communication along the gut-brain axis regulates inflammatory responses,21 and supporting gut health may reduce inflammation.14,22,23 A wide range of gastrointestinal (GI) symptoms and related inflammatory conditions may be treated starting with the functional medicine DIGIN framework. “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.

Further, IFM’s 5R framework (Remove, Replace, Repopulate, Repair, and Rebalance) helps support and heal the digestive tract. Functional medicine clinicians use these tools as well as IFM’s Functional Medicine Matrix and Timeline to develop individualized treatment strategies. IFM teaches clinicians the foundational background, insight, and in-depth clinical thinking to confidently assess and treat patients who may present with conditions, signs, and symptoms indicative of GI dysfunctions.

Future neurogastroenterology research will continue to cast light onto the gut-brain relationship and the effective therapies that address 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.24,25

Learn to recognize and treat the most important antecedents and triggers of GI dysfunction and implement therapeutic strategies at IFM’s GI Advanced Practice Module (APM).

Learn More About gut Dysfunction and Chronic Conditions

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The Microbiome, Stress Hormones, and Gut Function

IBS Development: Primary Causes & Triggers

Neurodegenerative Disease: Improving Outcomes Through Nutrition

References

  1. 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
  2. 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
  3. Kraimi N, Ross T, Pujo J, De Palma G. The gut microbiome in disorders of gut-brain interaction. Gut Microbes. 2024;16(1):2360233. doi:1080/19490976.2024.2360233
  4. 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
  5. 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
  6. Montalbán-Rodríguez A, Abalo R, López-Gómez L. From the gut to the brain: the role of enteric glial cells and their involvement in the pathogenesis of Parkinson’s disease. Int J Mol Sci. 2024;25(2):1294. doi:3390/ijms25021294
  7. Qu L, Li Y, Liu F, et al. Microbiota-gut-brain axis dysregulation in Alzheimer’s disease: multi-pathway effects and therapeutic potential. Aging Dis. 2024;15(3):1108-1131. doi:14336/AD.2023.0823-2
  8. Toader C, Dobrin N, Costea D, et al. Mind, mood and microbiota-gut-brain axis in psychiatric disorders. Int J Mol Sci. 2024;25(6):3340. doi:3390/ijms25063340
  9. 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
  10.  Ju S, Shin Y, Han S, et al. The gut-brain axis in schizophrenia: the implications of the gut microbiome and SCFA production. Nutrients. 2023;15(20):4391. doi:3390/nu15204391
  11.  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
  12.  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
  13.  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
  14.  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
  15.  Sikorska M, Antosik-Wójci?ska 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
  16.  Chen J, Yang N, Peng Y, Zhou H, Li Q. Association between nonfood pre- or probiotic use and cognitive function: results from NHANES 2011-2014. Nutrients. 2023;15(15):3408. doi:3390/nu15153408
  17.  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
  18.  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
  19.  Zagórska A, Marcinkowska M, Jamrozik M, Wi?niowska B, Pa?ko P. From probiotics to psychobiotics – the gut-brain axis in psychiatric disorders. Benef Microbes. 2020;11(8):717-732. doi:3920/BM2020.0063
  20.  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
  21.  Agirman G, Yu KB, Hsiao EY. Signaling inflammation across the gut-brain axis. Science. 2021;374(6571):1087-1092. doi:1126/science.abi6087
  22.  Bolte LA, Vich Vila A, Imhann F, et al. Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome. Gut. 2021;70(7):1287-1298. doi:1136/gutjnl-2020-322670
  23.  Illescas O, Rodríguez-Sosa M, Gariboldi M. Mediterranean diet to prevent the development of colon diseases: a meta-analysis of gut microbiota studies. Nutrients. 2021;13(7):2234. doi:3390/nu13072234
  24.  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
  25.  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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