For those of us who want to thrive in business and private life, maintaining cognitive performance and mental resilience as we age are major priorities. Research suggests that specific probiotic strains can influence brain function and overall cognitive health as the years pass. This interaction is possible because of the gut-brain axis - a bidirectional communication system between the brain and the central nervous system.
The probiotic strains B. breve MCC1274 and L. plantarum PS23 show the ability to support brain health and improve cognitive functions, including memory, in human clinical studies and preclinical studies (non-human lab-centered studies).
While human studies suggest that these probiotics may help with aspects of memory and cognition, they don’t explain how they help. But preclinical studies in animals allow researchers to take a closer look at the mechanism behind these remarkable strains. Results from preclinical studies of both MCC1274 and PS23 suggest roles for antioxidant function, immune response, neuroplasticity, and more.
Let’s take a look at the preclinical research to see how these "probiotics for your brain" might support healthy cognition in human aging.
B. breve MCC1274 supports brain health in preclinical studies
MCC1274 is a strain of Bifidobacterium breve with four human studies that explore its role in supporting brain processes and improving cognitive function. For example, a human randomized controlled trial study showed that MCC1274 improved immediate memory, delayed memory, and visuospatial/construction (related to spatial recognition) in people with suspected mild cognitive impairment.
How does it do this? Preclinical experiments suggest that MCC1274 supports cognition because of (1) antioxidant effects and (2) other biochemical processes that promote a healthy immune response in the brain and associated neuroplasticity.
MCC1274 may have antioxidant effects
Researchers hypothesized that the MCC1274 probiotic strain may help the brain by increasing levels of antioxidants that travel from the gut to the brain. To study this, healthy (“wild-type”) mice were given B. breve MCC1274 or saline in their water for four months. Then, the researchers took blood samples and analyzed the plasma metabolites of the mice to identify the mechanism underlying the probiotic’s beneficial effects.
These plasma metabolites are small molecules found in blood plasma that could be derived from microbial metabolism. Gut microbes use enzymes to break down products of food digestion in the intestines and these metabolites are byproducts of this process. In this case, researchers sought to identify which plasma metabolites were affected by supplementation with MCC1274 and if they were in any way beneficial.
The researchers found that B. breve supplementation significantly altered plasma metabolites in the mice. In particular, the scientists observed elevated levels of isoflavone metabolites - antioxidant compounds found to support brain function and reduce oxidative stress.
Oxidative stress is an imbalance between free radicals and antioxidants in the body. We need both types of molecules in the body to function, but problems arise when free radicals (natural byproducts of metabolism) outnumber the antioxidants.
While free radicals support the immune system and other processes, we only need low or moderate levels of them. Oxidative stress occurs when free radicals rise to unhealthy levels. In excess, they damage cells in the body, including those within the brain. In healthy aging, oxidative stress has been linked to cognitive issues, including memory problems and studies show that certain natural compounds can mediate the imbalance.
Isoflavones, flavonoids found in soy, have been shown in studies to improve cognitive function in healthy human adults. A previous preclinical study demonstrated that B. breve MCC1274 could increase the biotransformation of isoflavone as well as affect the gut microbial community. Therefore, MCC1274 may make these metabolites or indirectly influence their production by increasing the total numbers of beneficial gut microbes in the gut.
MCC1274 may support neuroplasticity in the brain
A remarkable characteristic of the brain is its adaptive ability to reorganize itself by forming, modifying, and strengthening neural connections. This is known as neuroplasticity, and it is partially influenced by the resident immune cells in the brain called microglia. In this placebo-controlled preclinical study, researchers found that MCC1274 may help balance the immune response of these microglial cells, which in turn promotes neuroplasticity and reduces oxidative activity.
Microglia play critical roles in supporting the central nervous system and promoting a healthy brain. They are highly dynamic and exist in multiple different states, but typically are described as being in either a resting or an activated state. They are the neuronal and immune support cells of the brain, where they are constantly sensing and regulating neuronal activity and, when activated, managing infection or injury.
When at “rest”, these cells are continually sensing the environment and pruning neural cells, both of which promote homeostasis and neuronal plasticity. Microglial cells in this non-activated state are involved in remodeling synapses and overall synaptic plasticity, which are critical to learning and memory.
In response to an injury or neurodegeneration, microglia become activated and change shape, secreting immune-activating proteins and reactive oxidative species. In aging, microglia have been found to transition into a hypersensitive and overactive state, which interferes with synaptic plasticity. In these cases, an intervention that attenuates, or calms, this overactive state helps the microglia return to the neural-supportive resting state.
In order to determine if MCC1274 supported brain health in healthy mice, researchers administered the probiotic and then used a series of tests to determine its effects. The mice were randomly assigned to either a probiotic or a placebo group. For four months, the probiotic group was administered B. breve MCC1274 (1 billion CFU) five times each week, whereas the placebo group simply was given saline.
At the end of the study, the researchers observed a reduction in the presence of a certain immune-reactive protein that is a marker for activated microglia, the immune cells of the brain. Thus, MCC1274 appeared to attenuate, or calm, microglial activation in healthy mice. This attenuation of the activated microglia serves to balance the overactivity and in turn support neuroplasticity.
Changes in other synaptic proteins in the hippocampus suggested a neuroprotective effect as well. The balancing effect on the immune response may help improve synaptic transmission and plasticity, which may help to maintain cognitive function, including the function of memory, in the aging brain.
L. paracasei PS23 supports healthy aging in preclinical studies
L. paracasei PS23 is a strain of the bacterial species Lacticaseibacillus paracasei with human studies reporting positive influences on stress regulation, emotional balance, and brain signaling pathways. Preclinical studies using PS23 in aging mice suggest that the probiotic may support healthy aging by helping to maintain cognitive function, including memory, and support muscle mass. While there is need for more research to fully understand its impact on human cognition, preclinical research helps us to understand the mechanisms that contribute to the probiotic’s beneficial actions.
In the following preclinical studies, scientists observed some remarkable changes in brain health and behavior in their animal models. These included improved memory and spatial awareness along with less anxiety-like behaviors.
The scientists attributed these beneficial changes to a healthy immune response in the PS23 group, a reduction in oxidative stress, and enhanced neuroplasticity - all of which promote brain health as we age. These proposed mechanisms are also quite similar to those seen in preclinical studies of MCC1274.
Studying PS23 in age-accelerated mice
Similar to humans, mice exhibit complex cognitive abilities, like spatial memory, learning, and social behaviors. They also share strikingly similar brain aging patterns with humans. Researchers often use age-accelerated mice as research models to evaluate cognition function and the impact of certain interventions, including probiotics. These preclinical studies help us to understand how probiotics work to benefit cognitive health in aging.
Studies have shown that aging in healthy mice can be accompanied by an increase in anxiety-like behaviors and a decline in cognitive function (i.e., spatial learning and memory).
Two recent PS23 preclinical studies utilized classic age-accelerated animal models to better understand the science underlying the probiotic’s cognitive benefits.6,7 In each randomized placebo-controlled study, the researchers divided the age-accelerated mice into at least a placebo group and probiotic group. Then, the researchers used behavioral tests, including the open field and Morris water maze tests, to observe stress-related and cognitive behaviors.
PS23 supports cognitive function in aging mice
To study cognitive function, scientists compared age-accelerated mice that took PS23 with those that took a placebo in behavioral tests as well as looking at levels of blood and brain tissue factors.
In behavioral tests, researchers observed clear spatial memory deficits in the aging placebo group. However, the aging PS23 group did not show these spatial memory deficits; their results were similar to non-aging mice. These results suggest that the probiotic ameliorated age-related memory deficits in mice.
These advantages of PS23 for spatial memory corresponded to higher levels of brain-derived neurotrophic factor (BDNF) and higher superoxide (SOD) enzyme levels. BDNF is a critical brain protein linked with neuroplasticity especially related to learning and memory.
SOD is considered one of the enzymes critical in the entire defense strategy of antioxidants. This enzyme was not only higher in the blood of aging mice taking PS23 compared with placebo, but was also higher in the hippocampus, the area of the brain important for memory.
In these studies, PS23 maintained SOD in the hippocampus during aging, while aging without the probiotic showed a reduction in SOD in the hippocampus. SOD decreases as we age, even if we are otherwise healthy. These findings in mice suggest that PS23 may ameliorate memory deficits and improve anxiety-related behaviors in aging.
PS23 might be the only probiotic that has been studied to show higher SOD in the brain.
These results suggest that supplementation of PS23 could be used as a strategy to support cognitive function (i.e., memory) in normal aging that may have an immune or oxidative stress component.
PS23 supports anxiety in aging mice
Similarly, behavioral and biochemical tests suggest an advantage of PS23 on anxiety in natural aging. In the open field test, the mice were placed in an open arena to observe cognitive as well as anxiety-related behaviors. Aging mice taking PS23 exhibited less anxiety-like behaviors in this test compared with aging mice taking placebo.6
These behavioral differences corresponded with higher levels of mood-stabilizing serotonin and dopamine in the brain tissue of the PS23 mice. They also had higher levels of BDNF in their blood. While BDNF is important for neuroplasticity, it is also important for mental health: low levels in certain regions of the brain are associated with anxiety and stress.
How do MCC1274 and PS23 benefit cognition?
MCC1274 and PS23 seem to benefit cognition through immune-balancing and antioxidant actions that benefit the brain via the gut-brain axis.
We have seen how MCC1274 increases levels of the antioxidant isoflavone metabolites in the blood and helps to calm the brain’s immune cells, or microglia, to help promote neuroplasticity. Similarly, scientists in both studies observed increased levels of the antioxidant enzyme SOD in the brain’s memory center, the hippocampus. SOD is the body’s primary defense against excessive free radical production, a major player in oxidative stress.
The PS23 strain was shown in preclinical models to increase levels of the crucial brain protein BDNF, which promotes learning, memory, and neuroplasticity. Both strains were shown to delay-age related cognitive decline in preclinical models by attenuating oxidative stress and supporting healthy brain signaling via the gut-brain axis.
The preclinical research we discussed here gives us a glimpse into the fascinating science underlying the probiotics’ positive effects on brain health, especially memory and stress-related behaviors. We have found that MCC1274 and PS23 may support cognition due to their influence on immune-related pathways in the brain. Through the gut-brain axis, these strains exert immune-balancing and antioxidant effects as shown in both preclinical and clinical studies.
References
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- Ohno, K., Abdelhamid, M., Zhou, C., Jung, C. G., & Michikawa, M. (2022).https://pmc.ncbi.nlm.nih.gov/articles/PMC9661342
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- Abdelhamid, M., Zhou, C., Jung, C. G., & Michikawa, M. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9231139/
- Cheng, L. H., Chou, P. Y., Hou, A. T., Huang, C. L., Shiu, W. L., Wang, S. (2022). https://pubmed.ncbi.nlm.nih.gov/35438699/
- Huang, S. Y., Chen, L. H., Wang, M. F., Hsu, C. C., Chan, C. H., Li, J. X., Huang, H. Y. (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6073302/
