While some things in life are best forgotten, our memories build the framework of intelligence \u2014 cognitive, emotional, and social \u2014 enabling a rich existence.<\/p>\n\n\n\n
Memory is required to learn a language, drive a car, write computer code, keep a friend and, of course, remember where you put the keys.<\/p>\n\n\n\n
Decades of research have revealed some of the mechanisms running this complex operation by which information is encoded, stored, and retrieved. The process is fallible though, affected most particularly by brain injury, disease, and aging. And as aging populations lead to more numbers of people with cognitive decline, researchers continue looking for therapies to prevent or treat memory impairment.<\/p>\n\n\n\n
The microbiome presents an emerging focus of interest. Could probiotics improve memory?<\/p>\n\n\n\n
Memory, in brief<\/strong><\/p>\n\n\n\n Evolutionary forces have designed a sophisticated system to create, store and retrieve memories.<\/p>\n\n\n\n Biological memory is an informational processing system with explicit and implicit functioning that is made up of a sensory processor, short-term (or working) memory, and long-term memory.<\/p>\n\n\n\n Memory and the microbiome<\/strong><\/p>\n\n\n\n Gut microbes communicate with the brain, and the brain with the gut along a bidirectional network known as the gut-brain axis<\/a>. The interplay between gut and brain involves a complex system of mediators and has been considered a critical target for the manipulation of brain health and neurodegenerative diseases<\/a>.<\/p>\n\n\n\n Cross talk takes many forms. There are five known pathways<\/a> through which the microbiota\u2013gut\u2013brain axis may modify cognitive function.<\/p>\n\n\n\n Let\u2019s take a closer look at several of these pathways studied in relation to memory.<\/p>\n\n\n\n Neural pathways<\/strong><\/p>\n\n\n\n Gut microbiota have the ability to synthesize key neurotransmitters<\/a> such as \u03b3-Aminobutyric acid (GABA), dopamine, acetylcholine, and serotonin. Notably, different bacteria produce different neurotransmitters and some may alter levels of precursors instead. Direct or indirect negative changes to cognition may reflect an altered microbiota.<\/p>\n\n\n\n A neurochemical, called brain-derived neurotrophic factor (BDNF), has a crucial role in memory storage and information processing. BDNF has emerged as an important regulator of mechanisms underlying long-term synaptic plasticity and memory formation<\/a> as well as in synaptogenesis.<\/p>\n\n\n\n Several studies<\/a> demonstrated that gut dysbiosis correlates with reduced expression of BDNF.<\/p>\n\n\n\n Immunological<\/strong><\/p>\n\n\n\n The brain\u2019s resident immune cells, the microglia, are under constant regulation by the gut microbiome<\/a>.<\/p>\n\n\n\n Dysbiosis may lead to increased permeability of the gut<\/a> and blood\u2013brain barrier<\/a> leading to easier passage of pathogens, damaged cells, and neurotoxins. The immune system responds to these harmful stimuli through a vital defense mechanism called inflammation, and acts by removing injurious stimuli and initiating the healing process.<\/p>\n\n\n\n However, a dysbiotic intestinal microbiota also produces and releases a mixture of metabolic products that increase the production of cytokines and inflammatory mediators<\/a>. These compounds may induce chronic inflammation in the brain leading to an increase in neurodegenerative processes.<\/p>\n\n\n\n Inflammation can lead to high production of free radicals at the site of infection thereby triggering oxidative stress<\/a>, which may lead to degenerative symptoms such as memory loss and decline of learning ability.<\/p>\n\n\n\n In addition, dysbiosis leads to altered production of important metabolic products of gut microbial activity such as SCFAs. Three SCFAs (acetic acid, propionic acid and butyric acid) are known to play a key role in microbiota\u2013gut\u2013brain crosstalk and have protective roles in neuropathological mechanisms<\/a>.<\/p>\n\n\n\n Probiotics<\/strong><\/p>\n\n\n\n Knowing the important role of the gut microbiota in brain health, researchers studied the effects of probiotic supplementation on memory.<\/p>\n\n\n\n Animal studies<\/em><\/p>\n\n\n\n Studies using various rodent models of aging and cognitive impairment generally showed encouraging results when probiotics were administered. The strains are not stated here in keeping with the International Probiotic Association reporting policy.<\/p>\n\n\n\n Human studies<\/em><\/p>\n\n\n\n Given the multiple interactions between the gut and the brain as well as the promising results with probiotics in animal memory studies, there has been sufficient premise to explore the gut microbiota as a target in human memory enhancement. <\/p>\n\n\n\n A 2021 review<\/a> reported that the gut microbiota of cognitively healthy and impaired elderly people may differ in the diversity and abundance of individual taxa, but specific taxa were not identified. However, some tendencies to altered Firmicutes\/Bacteroidetes<\/em> ratio were noted.<\/p>\n\n\n\n The effect of probiotics on memory has been studied in both community and clinical settings.<\/p>\n\n\n\n A recent study in older <\/a>adults found that in contrast to a placebo group, serum BDNF level was significantly increased at week 12 in the probiotics-treated group. BDNF has a crucial role in memory storage and information processing. In addition, a reduction in the relative abundances of Eubacterium<\/em> and Clostridiales in the gut driven by probiotic supplementation closely related to the increase in the serum BDNF, thereby improving brain functions.<\/p>\n\n\n\n The results of a meta-analysis<\/a> indicate that probiotics, when supplemented at adequate amounts for 12 weeks or longer, may improve cognitive function in mild cognitive impairment or individuals with Alzheimer\u2019s disease.<\/p>\n\n\n\n The effects of probiotics on memory specifically are often difficult to tease out of the heterogeneous research data. Numerous confounding factors may also affect the gut microbiota.<\/p>\n\n\n\n However, a systematic review and meta-analysis of randomized controlled trials titled The Effect of Prebiotics and Probiotics on Human Memory<\/em><\/a> was recently performed.<\/p>\n\n\n\n Here are studies included in the review with probiotics tested and outcomes on memory only. Link to the study for more detailed information on number of participants, duration of treatment and more.<\/p>\n\n\n\n Of note is the last study \u2014 a clinical study \u2014 that reported positive findings suggested to be the positive effects of the strain on the hippocampus. The other two showing effects were community-based.<\/p>\n\n\n\n When subject to meta-analysis, the group of studies showed the probiotics tested to have no effect on either short-term or long-term memory. <\/p>\n\n\n\n Takeaway<\/strong><\/p>\n\n\n\n There are several pathways through which the microbiota\u2013gut\u2013brain axis may modify cognitive function. But the effects of probiotic supplementation on human memory have not been as encouraging as those seen in animal studies.<\/p>\n\n\n\n The health-promoting effect of a probiotic depends on the strain, dose, and duration of treatment. The success of the intervention could be influenced by the hosts\u2019 diet and lifestyle, age, sex, geographic region, comorbidities, antibiotic exposure, and baseline microbiota composition.<\/p>\n\n\n\n Further research is needed.<\/p>\n\n\n\n Key references<\/strong><\/p>\n\n\n\n Athari Nik Azm, Somayeh et al. \u201cLactobacilli and bifidobacteria ameliorate memory and learning deficits and oxidative stress in \u03b2-amyloid (1-42) injected rats<\/a>.\u201d Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme<\/em> vol. 43,7 (2018): 718-726. doi:10.1139\/apnm-2017-0648<\/p>\n\n\n\n Bia\u0142ecka-D\u0119bek, Agata et al. \u201cGut Microbiota, Probiotic Interventions, and Cognitive Function in the Elderly: A Review of Current Knowledge<\/a>.\u201d Nutrients<\/em> vol. 13,8 2514. 23 Jul. 2021, doi:10.3390\/nu13082514<\/p>\n\n\n\n Chung, Y.C., et al (2014). Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults<\/a>. Journal of Functional Foods, 10<\/em>, 465- 474.<\/p>\n\n\n\n Cunha, Carla et al. \u201cA simple role for BDNF in learning and memory?<\/a>.\u201d Frontiers in molecular neuroscience<\/em> vol. 3 1. 9 Feb. 2010, doi:10.3389\/neuro.02.001.2010<\/p>\n\n\n\n Deidda, Gabriele, and Manuele Biazzo. \u201cGut and Brain: Investigating Physiological and Pathological Interactions Between Microbiota and Brain to Gain New Therapeutic Avenues for Brain Diseases.<\/a>\u201d Frontiers in neuroscience<\/em> vol. 15 753915. 12 Oct. 2021, doi:10.3389\/fnins.2021.753915<\/p>\n\n\n\n Dinan, Timothy G, and John F Cryan. \u201cGut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration<\/a>.\u201d The Journal of physiology<\/em> vol. 595,2 (2017): 489-503. doi:10.1113\/JP273106<\/p>\n\n\n\n Dinan, Timothy G, and John F Cryan. \u201cThe Microbiome-Gut-Brain Axis in Health and Disease.<\/a>\u201d Gastroenterology clinics of North America<\/em> vol. 46,1 (2017): 77-89. doi:10.1016\/j.gtc.2016.09.007<\/p>\n\n\n\n Erny, Daniel et al. \u201cHost microbiota constantly control maturation and function of microglia in the CNS<\/a>.\u201d Nature neuroscience<\/em> vol. 18,7 (2015): 965-77. doi:10.1038\/nn.4030<\/p>\n\n\n\n Gao, Wen et al. \u201cThe Gut Microbiome as a Component of the Gut-Brain Axis in Cognitive Health.<\/a>\u201d Biological research for nursing<\/em> vol. 22,4 (2020): 485-494. doi:10.1177\/1099800420941923<\/p>\n\n\n\n Ho, Shang-Tse et al. \u201cImproving effect of a probiotic mixture on memory and learning abilities in d-galactose-treated aging mice.\u201d<\/a> Journal of dairy science<\/em> vol. 102,3 (2019): 1901-1909. doi:10.3168\/jds.2018-15811<\/p>\n\n\n\n Hwang, Yun-Ha et al. \u201cEfficacy and Safety of Lactobacillus Plantarum<\/em> C29-Fermented Soybean (DW2009) in Individuals with Mild Cognitive Impairment: A 12-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial<\/a>.\u201d Nutrients<\/em> vol. 11,2 305. 1 Feb. 2019, doi:10.3390\/nu11020305<\/p>\n\n\n\n Kim, Chong-Su et al. \u201cProbiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial<\/a>.\u201d The journals of gerontology. Series A, Biological sciences and medical sciences<\/em> vol. 76,1 (2021): 32-40. doi:10.1093\/gerona\/glaa090<\/p>\n\n\n\n Kobayashi, Y et al. \u201cEffects of Bifidobacterium breve<\/em> A1 on the cognitive function of older adults with memory complaints: a randomised, double-blind, placebo-controlled trial<\/a>.\u201d Beneficial microbes<\/em> vol. 10,5 (2019): 511-520. doi:10.3920\/BM2018.0170<\/p>\n\n\n\n Lew, Lee-Ching et al. \u201cProbiotic Lactobacillus plantarum P8 alleviated stress and anxiety while enhancing memory and cognition in stressed adults: A randomised, double-blind, placebo-controlled study.<\/a>\u201d Clinical nutrition (Edinburgh, Scotland)<\/em> vol. 38,5 (2019): 2053-2064. doi:10.1016\/j.clnu.2018.09.010<\/p>\n\n\n\n Lin, Shih-Wei et al. \u201cLactobacillus plantarum<\/em> GKM3 Promotes Longevity, Memory Retention, and Reduces Brain Oxidation Stress in SAMP8 Mice<\/a>.\u201d Nutrients<\/em> vol. 13,8 2860. 20 Aug. 2021, doi:10.3390\/nu13082860<\/p>\n\n\n\n Logsdon, Aric F et al. \u201cGut reactions: How the blood-brain barrier connects the microbiome and the brain.<\/a>\u201d Experimental biology and medicine (Maywood, N.J.)<\/em> vol. 243,2 (2018): 159-165. doi:10.1177\/1535370217743766<\/p>\n\n\n\n Maiuolo, Jessica et al. \u201cThe Contribution of Gut Microbiota-Brain Axis in the Development of Brain Disorders<\/a>.\u201d Frontiers in neuroscience<\/em> vol. 15 616883. 23 Mar. 2021, doi:10.3389\/fnins.2021.616883<\/p>\n\n\n\n Ohsawa, Kazuhito et al. \u201cLactobacillus helveticus-fermented milk containing lactononadecapeptide (NIPPLTQTPVVVPPFLQPE) improves cognitive function in healthy middle-aged adults: a randomised, double-blind, placebo-controlled trial<\/a>.\u201d International journal of food sciences and nutrition<\/em> vol. 69,3 (2018): 369-376. doi:10.1080\/09637486.2017.1365824<\/p>\n\n\n\n Rudzki, Leszek et al. \u201cProbiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study<\/a>.\u201d Psychoneuroendocrinology<\/em> vol. 100 (2019): 213-222. doi:10.1016\/j.psyneuen.2018.10.010<\/p>\n\n\n\n Sanborn, Victoria et al. \u201cRandomized Clinical Trial Examining the Impact of Lactobacillus rhamnosus<\/em> GG Probiotic Supplementation on Cognitive Functioning in Middle-aged and Older Adults<\/a>.\u201d Neuropsychiatric disease and treatment<\/em> vol. 16 2765-2777. 13 Nov. 2020, doi:10.2147\/NDT.S270035<\/p>\n\n\n\n Wang, QuanQiu et al. \u201cGut-microbiota-microglia-brain interactions in Alzheimer’s disease: knowledge-based, multi-dimensional characterization<\/a>.\u201d Alzheimer’s research & therapy<\/em> vol. 13,1 177. 20 Oct. 2021, doi:10.1186\/s13195-021-00917-1<\/p>\n\n\n\n Xiao, Jinzhong et al. \u201cProbiotic Bifidobacterium breve in Improving Cognitive Functions of Older Adults with Suspected Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial.<\/a>\u201d Journal of Alzheimer’s disease : JAD<\/em> vol. 77,1 (2020): 139-147. doi:10.3233\/JAD-200488<\/p>\n\n\n\n Yang, Xueqin et al. \u201cProbiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice<\/a>.\u201d Acta pharmaceutica Sinica. B<\/em> vol. 10,3 (2020): 475-487. doi:10.1016\/j.apsb.2019.07.001<\/p>\n\n\n\n\n
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