Brain-derived neurotrophic factor (BDNF), a neurotrophic protein, is one of several factors related to the function of degenerating neurons and development of AD. The level of serum BDNF has been found to be significantly lower in AD patients than in healthy individuals.
Some studies have pointed out the potential effect of probiotics in improving cognitive function via the gut-brain axis in older adults. However, clinical trials evaluating the efficacy of probiotics targeting neurotrophic factors and inflammatory biomarkers are limited.
Therefore, a group of researchers in Taiwan conducted a randomised, double-blinded, active-controlled trial from 2020 to 2022 to investigate the effects of multi-strain probiotic intervention in clinically diagnosed AD patients.
A total of 32 participants, who were randomly assigned to either the active control group or the treatment group, completed the trial.
They were instructed to take one capsule daily for a period of 12 weeks. The probiotic supplement of the treatment group contained 1 × 1010 CFU per capsule, while that of the active control group contained 5 × 107 CFU per capsule.
Each capsule comprised a combination of five probiotic strains, namely Bifidobacterium longum subsp. infantis BLI-02, B. breve Bv-889, B. animalis subsp. lactis CP-9, B. bifidum VDD088, and Lactobacillus plantarum PL-02, in equal proportions.
All probiotic strains were sourced from Glac Biotech Co Ltd, which also supported the study with a grant.
After the 12-week intervention, the treatment group demonstrated a 36% increase in serum BDNF, a reduction in inflammatory cytokine IL-1β (p = 0.041), and an increase in antioxidant superoxide dismutase (SOD) activity (p = 0.012). No significant change was found in the active control group.
Although there were no significant improvements in cognitive function after the intervention, the scores of the treatment group showed a trend of lowering the rate at which AD symptoms worsen.
“The findings of this clinical trial, even with a short period of intervention in a small sample size, provide evidence supporting the positive impact of multi-strain probiotics in AD patients. With sufficient doses and a proper formulation of probiotic supplementation, serum BDNF can be enhanced along with a reduction in oxidative stress and an increase in antioxidants.
“Probiotics may also have potential benefits in slowing the decline in cognitive function among symptomatic AD patients. To confirm the efficacy of these probiotics, further studies with longer intervention and follow-up durations, a larger sample size, as well as repeated assessment of faecal microbes after patients have completed their supplement intake, are needed,” the authors wrote.
Link between gut microbiota and neurodegenerative diseases
AD is an irreversible form of neurodegenerative disorder that leads to cognitive impairment, memory loss, and disruptions in brain function. It is characterised by the deposition of amyloid plaques, abnormal phosphorylation of tubulin-associated unit (TAU) proteins in the brain, and degeneration of neurons.
While there are medications that help provide temporary improvement in memory, they do not alter the progression of AD.
In recent years, numerous studies have highlighted the relationship between the gut microbiome and the central nervous system, commonly referred to as the gut-brain axis.
Gut dysbiosis, an imbalance in the gut microbial community, is believed to contribute to the development and progression of AD.
“Imbalance of the gut microbiota can lead to reduced levels of BDNF in the hippocampus and cortical midbrain, potentially inducing cognitive impairment through the gut-brain axis.
“Multiple reports have shown that bacterial diversity is decreased in AD patients, with reductions in Firmicutes and Bifidobacterium, and an increase in Bacteroidetes and Actinobacteria.”
In addition, there is data indicating that higher levels of Clostridium are associated with better cognitive performance.
“Butyrate-producing bacteria, such as Ruminococcus and Clostridium, have been verified to metabolise unprocessed carbohydrates, resulting in the generation of short-chain fatty acids (SCFAs) and lactic acid within the intestine.
“SCFAs are also thought to modulate the effects of BDNF in the central nervous system. This metabolic process supports the proliferation of Lactobacillus and Bifidobacterium.”
Probiotics have gained attention for their ability to restore the homeostasis of intestinal microbiota, with benefits extending beyond digestive health.
Research has also suggested that a combination of Lactobacillus and Bifidobacterium can effectively increase BDNF levels in individuals with neurological disorders, contributing to improved cognitive function.
In this study, the treatment group experienced an increase in the abundance of Bifidobacterium (1.3% to 3.9%), Lactobacillus (0.1% to 0.3%), Ruminococcus (2.9% to 4.8%), Clostridium (4.6% to 6.4%), and Akkermansia (0.9% to 1.0%) at the genera level.
Conversely, the presence of harmful bacteria Megamonas (4.8% to 1.5%) decreased in the treatment group.
However, these changes at the phyla and genera levels were not significantly different after the 12-week intervention.
“Several factors can affect human microbiota, such as diet, environment, medication, and mood. The small number of participants may also lead to the insignificant result of this short-term intervention.”
“Efficacy of Probiotic Supplements on Brain-Derived Neurotrophic Factor, Inflammatory Biomarkers, Oxidative Stress and Cognitive Function in Patients with Alzheimer’s Dementia: A 12-Week Randomized, Double-Blind Active-Controlled Study”
Authors: Yu-Chieh Hsu, et al