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Gut Microbiome and Cognitive Health: Unveiling the Surprising Connection

As surprising as it may sound, bacteria present in your gut are known to play a crucial role in our health. They are believed to help in the supply of essential nutrients, aid in the digestion of cellulose, synthesize vitamin K, and have many other essential roles. A new study has not found an association between these beneficial microorganisms in our gut and cognitive health. Read on to find out more about the link between microorganisms in the gut and your cognitive function. 

Gut Microbiome and its Impact on our Health

In recent years, researchers have been working round the clock to discover the many ways in which bacteria living in our gastrointestinal tract influence our health. These microorganisms, collectively known as the microbiome or gut microbiome, are known to be amazingly diverse, and the past few years have witnessed a wide variety of research studies that looked at this amazing association. (1,2,3)

There have been many studies carried out on animals and small clinical studies in the past that have discovered changes in cognition linked to specific changes in the microbiome of the gut. However, there have been very few studies that actually looked at the gut microbiome and its association with cognition in large samples within a community setting. (4,5)

In February 2022, researchers from the United States published their analysis of data from a large cross-sectional study. The study discovered an association between the composition of gut bacteria and the cognitive condition of middle-aged adults. The participants of the study were taken from four centers across the US and were part of the bigger CARDIA (Coronary Artery Risk Development in Young Adults) study. (6,7)

The findings of this recent study have further added weight to the growing body of data that suggests that gut bacteria might be closely linked to cognitive aging. The results of this study were published in February 2022 in the JAMA Neurology journal. The study provided a deep insight into how bacteria, our overall environments, and individual health behaviors have an impact on our cognitive health. While many of these factors have been studied in separate studies independently, as well as in animal studies, but this particular study looked at all these factors together, and that too within a community-dwelling sample for the first time with the use of existing data from the CARDIA study.

What Did The Study Show About the Link Between Gut Microbiome and Cognitive Health?

As mentioned, the research team used the data that the CARDIA study team had already collected. CARDIA was a population-based research study that looked at white and black adults living in four specific areas – Minneapolis, Birmingham (Alabama), Oakland (California), and Chicago. There were 3358 participants in the study, and they all underwent a 30-year follow-up in 2015-2016. All the participants were given several cognitive assessments as part of the study, and 3124 participants completed at least one evaluation during the time period of the study. (8,9)

Apart from this, 615 participants of the study were further made a part of a gut microbiome sub-study that collected their stool samples and sent them to a central laboratory where they underwent DNA sequencing.

In the meantime, the participants had completed six cognitive tests, including the times Stroop test, letter fluency, the Digit Symbol Substitution Test (DSST), category fluency, the Montreal Cognitive Assessment, and the Rey-Auditory Verbal Learning Test. The results of the cognitive tests were also collected, and each participant was given a summary score. (10,11,12,13)

The research team also accounted for any other factors that could influence the test scores as well as the microbiome composition of the participants. These factors were terms as confounders, and they included the following:

Data was also collected on comorbidities like diabetes and hypertension that may have an impact on the results.

Out of the 615 participants who took part in the microbiome sub-study, 607 were found to have stool samples that passed the requirements of DNA sequencing. Ten participants did not complete the data required for the cognitive tests, which means that the ultimate analysis was done on data from 597 participants instead of 615.

All the participants were in the age group of 48 to 60 years, and out of these, 44.7 percent were men, 45.2 percent were Black, and 44.8 percent were white.

The analysis zeroed in on three main areas:

  • Between-person microbial diversity
  • Within-person microbial diversity
  • Individual composition of microorganisms in the stool samples

In the focus area of between-person differences, the bacterial composition was found to be substantially associated with cognitive measures after adjusting for the risk factors. The researchers also observed that there was a statistically significant interaction by gender, though there was not much of a difference in the results based on race.

Compared to this, the focus area of within-person microbial diversity was not really linked with cognition in the data collected. Once the results were completely adjusted for any of the confounding factors, it was found that the bacteria Akkermansia, Barnesiella, and Lachnospiraceae were positively linked with at least one of the cognitive tests. At the same time, Sutterella was negatively linked with the Montreal Cognitive Assessment test.

Mechanism Behind the Findings

One potential mechanism that is believed to explain the results of the study is the production of short-chain fatty acids. Short-chain fatty acids are one of the significant byproducts of the microbiome and could have potential neuroactive properties. (14,15) Researchers believe that short-chain fatty acids play an important part in controlling how the gut and brain interact or the functioning of the gut-brain axis. (16,17,18)

In many animal studies, short-chain fatty acids were found to protect against cognitive impairment and vascular dementia. (19,20) Due to these studies, there already was some amount of solid evidence that nutrition is associated with the microbiome composition of the body, and both these factors are, in turn, linked to cognitive function and other health factors.

The benefit of this particular study was that it provided data from a larger group of participants than the previous studies had access to, thus further supporting the association of gut microbiome with cognitive health.

However, there were still some restrictions on the study. The sample size was still small, especially when used for multiple comparisons and multiple cognitive tests. At the same time, measuring the gut microbiome from just one stool sample did not capture the between-person microbial differences consistently as the composition continues to change over time. Also, any changes in the health of the participants may have caused shifts in the bacterial community.

Conclusion

The study authors believe that more work is still needed to confirm the results, preferably using whole-metagenomics sequencing, known as shotgun sequencing. Shotgun sequencing is a faster method of DNA sequencing and is capable of providing more information on the metabolic pathways as well as the interactions taking place in the gut microbiome. Nevertheless, the study did manage to provide sufficient data to show the association between gut bacteria and cognitive health.

References:

  1. DeMartino, P. and Cockburn, D.W., 2020. Resistant starch: impact on the gut microbiome and health. Current opinion in biotechnology, 61, pp.66-71.
  2. Hajela, N., Ramakrishna, B.S., Nair, G.B., Abraham, P., Gopalan, S. and Ganguly, N.K., 2015. Gut microbiome, gut function, and probiotics: Implications for health. Indian Journal of Gastroenterology, 34(2), pp.93-107.
  3. Singh, R.K., Chang, H.W., Yan, D.I., Lee, K.M., Ucmak, D., Wong, K., Abrouk, M., Farahnik, B., Nakamura, M., Zhu, T.H. and Bhutani, T., 2017. Influence of diet on the gut microbiome and implications for human health. Journal of translational medicine, 15(1), pp.1-17.
  4. Minter, M.R., Hinterleitner, R., Meisel, M., Zhang, C., Leone, V., Zhang, X., Oyler-Castrillo, P., Zhang, X., Musch, M.W., Shen, X. and Jabri, B., 2017. Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE/PS1ΔE9 murine model of Alzheimer’s disease. Scientific reports, 7(1), pp.1-18.
  5. Gareau, M.G., 2016. Cognitive function and the microbiome. International review of neurobiology, 131, pp.227-246.
  6. Meyer, K., Lulla, A., Debroy, K., Shikany, J.M., Yaffe, K., Meirelles, O. and Launer, L.J., 2022. Association of the gut microbiota with cognitive function in midlife. JAMA network open, 5(2), pp.e2143941-e2143941.
  7. Friedman, G.D., Cutter, G.R., Donahue, R.P., Hughes, G.H., Hulley, S.B., Jacobs Jr, D.R., Liu, K. and Savage, P.J., 1988. CARDIA: study design, recruitment, and some characteristics of the examined subjects. Journal of clinical epidemiology, 41(11), pp.1105-1116.
  8. Pereira, M.A., Kartashov, A.I., Ebbeling, C.B., Van Horn, L., Slattery, M.L., Jacobs Jr, D.R. and Ludwig, D.S., 2005. Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis. The lancet, 365(9453), pp.36-42.
  9. Dyer, A.R., Liu, K., Walsh, M., Kiefe, C., DR Jr, J. and Bild, D.E., 1999. Ten-year incidence of elevated blood pressure and its predictors: the CARDIA study. Journal of human hypertension, 13(1), pp.13-21.
  10. Tsoi, K.K., Chan, J.Y., Hirai, H.W., Wong, S.Y. and Kwok, T.C., 2015. Cognitive tests to detect dementia: a systematic review and meta-analysis. JAMA internal medicine, 175(9), pp.1450-1458.
  11. Chen, P., Ratcliff, G., Belle, S.H., Cauley, J.A., DeKosky, S.T. and Ganguli, M., 2000. Cognitive tests that best discriminate between presymptomatic AD and those who remain nondemented. Neurology, 55(12), pp.1847-1853.
  12. Jaeger, J., 2018. Digit symbol substitution test: the case for sensitivity over specificity in neuropsychological testing. Journal of clinical psychopharmacology, 38(5), p.513.
  13. All, O.C.N.F., 2015. Montreal Cognitive Assessment. Stroke.
  14. Cook, S.I. and Sellin, J.H., 1998. Short chain fatty acids in health and disease. Alimentary pharmacology & therapeutics, 12(6), pp.499-507.
  15. Tan, J., McKenzie, C., Potamitis, M., Thorburn, A.N., Mackay, C.R. and Macia, L., 2014. The role of short-chain fatty acids in health and disease. Advances in immunology, 121, pp.91-119.
  16. Silva, Y.P., Bernardi, A. and Frozza, R.L., 2020. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Frontiers in endocrinology, 11, p.25.
  17. Dalile, B., Van Oudenhove, L., Vervliet, B. and Verbeke, K., 2019. The role of short-chain fatty acids in microbiota–gut–brain communication. Nature reviews Gastroenterology & hepatology, 16(8), pp.461-478.
  18. Van de Wouw, M., Boehme, M., Lyte, J.M., Wiley, N., Strain, C., O’Sullivan, O., Clarke, G., Stanton, C., Dinan, T.G. and Cryan, J.F., 2018. Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations. The Journal of physiology, 596(20), pp.4923-4944.
  19. Liu, J., Sun, J., Wang, F., Yu, X., Ling, Z., Li, H., Zhang, H., Jin, J., Chen, W., Pang, M. and Yu, J., 2015. Neuroprotective effects of Clostridium butyricum against vascular dementia in mice via metabolic butyrate. BioMed research international, 2015.
  20. Sun, J., Ling, Z., Wang, F., Chen, W., Li, H., Jin, J., Zhang, H., Pang, M., Yu, J. and Liu, J., 2016. Clostridium butyricum pretreatment attenuates cerebral ischemia/reperfusion injury in mice via anti-oxidation and anti-apoptosis. Neuroscience Letters, 613, pp.30-35.

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Sheetal DeCaria, M.D.
Sheetal DeCaria, M.D.
Written, Edited or Reviewed By: Sheetal DeCaria, M.D. This article does not provide medical advice. See disclaimer
Last Modified On:December 5, 2023

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