Probiotic Supplementation in Patients with Alzheimer's Dementia - An Explorative Intervention Study

Abstract

Background: Dysbiosis of intestinal microbiota in the elderly can cause a leaky gut, which may result in silent systemic inflammation and promote neuroinflammation - a relevant pathomechanism in the early course of Alzheimer's disease.

Objective: The rebalancing of the microbiome could benefically impact on gut inflammation and immune activation.

Methods: In this study, routine laboratory tests in twenty outpatients (9 females, 11 males, aged 76.7 ± 9.6 years) with Alzheimer's disease were investigated. The mean Mini Mental State Examination score was 18.5 ± 7.7. Biomarkers of immune activation - serum neopterin and tryptophan breakdown - as well as gut inflammation markers and microbiota composition in fecal specimens were analyzed in 18 patients before and after probiotic supplementation for 4 weeks.

Results: After treatment a decline of fecal zonulin concentrations and an increase in Faecalibacterium prausnitzii compared to baseline were observed. At the same time, serum kynurenine concentrations increased (p <0.05). Delta values (before - after) of neopterin and the kynurenine to tryptophan ratios (Kyn/Trp) correlated significantly (p <0.05).

Conclusion: Results show that the supplementation of Alzheimer's disease patients with a multispecies probiotic influences gut bacteria composition as well as tryptophan metabolism in serum. The correlation between Kyn/Trp and neopterin concentrations points to the activation of macrophages and/or dendritic cells. Further studies are warranted to dissect the potential consequences of Probiotic supplementation in the course of Alzheimer's disease.

Keywords: Alzheimer`s disease; Faecalibacterium prausnitzii; Gut microbiota; brain-gut axis; dementia; neopterin; neuroinflammation; probiotics..

Fig. (1)

The proposed role of immune activation arms in Alzheimer’s disease (AD). (A) Oxidative stress is associated with Th1-type immunity and suppresses the Th2-arm, and vice versa. Both, the composition of diet and the microbiome, influence immune homeostasis in a physiological range. While the establishment of tolerance requires more Th2-like conditions, a deviation to pro-oxidative Th1 is necessary for an efficient removal of pathogens, tumor cells and amyloid proteins. The preponderance of a strong reductive milieu, e.g., due to excessive intake of food antioxidants and likewise the presence of chronic oxidative stress are crucial in the progression of a variety of disorders. (B) Corresponding hypothesis: It is suggested that in early stages of AD there is an inefficient clearance from amyloid precursors, potentially due to overwhelming Th2 conditions which in the course of disease development from mild cognitive impairment (MCI) to AD promote an activation of counteracting Th1-type immune mechanisms that also lead to neuronal damage.