While some things in life are best forgotten, our memories build the framework of intelligence — cognitive, emotional, and social — enabling a rich existence.
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.
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.
The microbiome presents an emerging focus of interest. Could probiotics improve memory?
Memory, in brief
Evolutionary forces have designed a sophisticated system to create, store and retrieve memories.
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.
- Sensory memory —an automatic response— holds information, derived from the senses, less than one second after an item is perceived.
- Short-term memory is also known as working memory. Short-term memory allows recall for a period of several seconds to a minute without rehearsal.
- Long-term memory can store much larger quantities of information for potentially unlimited duration (sometimes a whole life span).
Memory and the microbiome
Gut microbes communicate with the brain, and the brain with the gut along a bidirectional network known as the gut-brain axis. 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.
Cross talk takes many forms. There are five known pathways through which the microbiota–gut–brain axis may modify cognitive function.
- Evidence in both animal models and humans suggests that gut microbiota dysbiosis increases hypothalamic–pituitary–adrenal (HPA) axis reactivity, thereby contributing to impaired memory and learning.
- Gut microbiota and metabolites can trigger an inflammatory response that interacts with the blood–brain barrier, leading to increased permeability.
- Products of the microbiota such as short-chain fatty acids (SCFA) directly or indirectly stimulate the vagal nerve.
- Gut microbiota produce or consume a variety of neurotransmitters and hormones that modify central nervous system function.
- Gut microbiota activity can induce modification of myelination, myelin plasticity, and microRNA expression in the prefrontal cortex, an area important for complex cognitive tasks such as planning and decision-making.
Let’s take a closer look at several of these pathways studied in relation to memory.
Gut microbiota have the ability to synthesize key neurotransmitters such as γ-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.
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 as well as in synaptogenesis.
Several studies demonstrated that gut dysbiosis correlates with reduced expression of BDNF.
The brain’s resident immune cells, the microglia, are under constant regulation by the gut microbiome.
Dysbiosis may lead to increased permeability of the gut and blood–brain barrier 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.
However, a dysbiotic intestinal microbiota also produces and releases a mixture of metabolic products that increase the production of cytokines and inflammatory mediators. These compounds may induce chronic inflammation in the brain leading to an increase in neurodegenerative processes.
Inflammation can lead to high production of free radicals at the site of infection thereby triggering oxidative stress, which may lead to degenerative symptoms such as memory loss and decline of learning ability.
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–gut–brain crosstalk and have protective roles in neuropathological mechanisms.
Knowing the important role of the gut microbiota in brain health, researchers studied the effects of probiotic supplementation on memory.
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.
- A mixture of strains of Lactobacillus acidophilus, L. fermentum, Bifidobacterium lactis, and B. longum administered for 8 weeks in an experimental rat model of Alzheimer’s disease ameliorated memory and learning deficits.
- L. paracasei ssp. paracasei, L. plantarum, and Streptococcus thermophilus probiotic mixture improved memory and learning abilities and ameliorated the apoptosis pattern in the hippocampus of aging mice treated with d-galactose.
- A probiotic preparation composed of B. lactis, L. casei, B. bifidum, and L. acidophilus was administered to senescence-accelerated mouse prone 8 (SAMP8) mice for 12 weeks. Results showed improvement in memory deficits as well as other age related disruptions along the gut brain axis.
- L. plantarum used in the SAMP8 mice model delayed the process of aging, improved memory retention and reduced oxidative stress.
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.
A 2021 review 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 ratio were noted.
The effect of probiotics on memory has been studied in both community and clinical settings.
A recent study in older 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 and Clostridiales in the gut driven by probiotic supplementation closely related to the increase in the serum BDNF, thereby improving brain functions.
The results of a meta-analysis 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’s disease.
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.
However, a systematic review and meta-analysis of randomized controlled trials titled The Effect of Prebiotics and Probiotics on Human Memory was recently performed.
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.
- Lactobacillus helveticus (Chung et al. 2014):no significant difference
- L. plantarum (Hwang et al. 2019):no significant difference
- L. plantarum (Lew et al. 2018): Intervention effect on long-term memory but not short-term memory
- Bifidobacterium bifidum and B. longum (Kim et al. 2021): Intervention effect on short-term memory but not long-term
- B. breve (Kobayashi et al. 2019): no significant difference
- L. Helveticus (Ohsawa et al. 2018): no significant difference
- L. plantarum (Rudzki et al. 2019): no significant difference
- L. rhamnosus (Sanborn et al. 2020): no significant difference
- B. breve (Xiao et al. 2020): Intervention effect on both short and long term memory
Of note is the last study — a clinical study — that reported positive findings suggested to be the positive effects of the strain on the hippocampus. The other two showing effects were community-based.
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.
There are several pathways through which the microbiota–gut–brain 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.
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’ diet and lifestyle, age, sex, geographic region, comorbidities, antibiotic exposure, and baseline microbiota composition.
Further research is needed.
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