Italian researchers fed mice a probiotic formula for four months and measured cognitive function. The results were very promising.
Transgenic mice in the early stage of Alzheimer’s (technically the animal model version of the disease) were given a probiotic formula of lactic acid bacteria and bifidobacteria starting at 8 weeks of age. The treatment group and the control group were measured at various ages for performance on the Open Field (OF) test and the Novel Object Recognition (NOR) test. Numerous tests were also performed on biological functions.
The results clearly showed that the probiotic formula protected the Alzheimer’s mice from neurodegeneration as measured by cognitive function and signs of brain damage.
Into The Weeds
The study (Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial) used two groups of mice (treated and untreated). Each group was a 50/50 mix of triple-transgenic mice (engineered to have three Alzheimer’s associated gene expressions) and “wild type” mice whose microbiota are more robust than regular lab mice.
The researchers looked for all kinds of things. Here are some highlights.
- Plasma hormone concentrations for ghrelin, leptin, GIP, and GLP-1.
- Plasma levels of pro- and anti-inflammatory cytokines.
- Amyloid-beta (Aß-42)
- Fibroblast growth factor 9
- Cortex size
- Apoptotic index
- Proteasome peptidase activities
- Cathepsin B & L
- and Autophagy related proteins
The wild type mice performed at normal levels that were no different between the treated and untreated groups. Therefore, probiotic treatment did not change the performance or measures for wild type mice, although it did increase their Bifidobacterium spp. and reduced Campylobacterales (i.e. Helicobacteriaceae).
Among the triple-transgenic mice the differences were large. As expected, the untreated transgenic mice deteriorated over the course of the testing. Transgenic mice that received the probiotic formula fared much better.
Transgenic mice in the treated group showed less cognitive decline after ten weeks on the probiotic formula. Their hippocampal FGFP expression was better. Their brain weight was unchanged and cortical thickness was much better, especially over time. 14 metabolic pathways were increased in the transgenic mice, “including DNA repair, pyrimidine metabolism, transcription machinery, energy metabolism, and glycolysis-cluconeogenesis.”
Transgenic mice on the probiotic formula showed reduced levels of pro-inflammatory cytokines. Anti-inflammatory cytokines were increased. Ghrelin and GIP were increased significantly from 18 to 24 weeks. GLP-1 levels increased after just 4 weeks of treatment.
Aß-42 load was significantly decreased with no change in Aß-40 levels. Accumulation of amyloid oligomers found a considerable reduction. Aß plaques had a significant reduction of extracellular amyloid deposits. Cathepsin B and L, associated with suppressing Aß levels, also showed changes with cathepsin B activity decreasing and cathepsin L activity increases to levels that rivaled those of the wild type mice.
Transgenic mice had partially restored proteasome activity (the breakdown and recycling of misfolded proteins) and a reduced apoptotic index at the neuronal level, especially in the dentate gyrus (part of the hippocampus).
The results show that the “wild type” mice (with a naturally more robust microbiota) did not experience symptoms of Alzheimer’s pathologies regardless of whether they received the probiotic formula or not. However, the probiotic formula may have protected them from other maladies not considered as part of this study. Specifically, the increase of Bifidobacterium spp. and reduction of Campylobacterales (i.e. Helicobacteriaceae). As we have seen before, Bifidobacterium reduces the permeability of the gut and inhibits inflammation. By reducing the possibility of a leaky gut, Bifidobacterium inhibits the ability of Helicobacteriaceae, a gram-negative bacteria, to enter the bloodstream where the LPS from its outer membrane can trigger systemic inflammation and cross the blood brain barrier where it combines with plaque deposits and exacerbates tau pathology.
The untreated transgenic mice, however, experienced a normal progression of neurodegeneration with all the hallmarks of reduced brain weight, a thinner cortex, cognitive decline, Aß plaques, and inflammation. The exciting results are from the group of treated transgenic mice who saw improvement over their untreated brethren in all these areas.
The study clearly demonstrates that a probiotic formula can alter the microbiota and those changes can be beneficial for the brain.