In recent years, commensal bacteria colonizing the human body have been recognized as important determinants of health and multiple pathologic conditions. Among the most extensively studied commensal bacteria are the gut microbiota, which perform a plethora of functions, including the synthesis of bioactive products, metabolism of dietary compounds, and immunomodulation, both through attenuation and immunostimulation. An imbalance in the microbiota population, i.e., dysbiosis, has been linked to many human pathologies, including various cancer types and neurodegenerative diseases. Targeting gut microbiota and microbiome–host interactions resulting from probiotics, prebiotics, and postbiotics is a growing opportunity for the effective treatment of various diseases. As more research is being conducted, the microbiome field is shifting from simple descriptive analysis of commensal compositions to more molecular, cellular, and functional studies. Insight into these mechanisms is of paramount importance for understanding and modulating the effects that microbiota, probiotics, and their derivatives exert on host health.

Herein we gathered updated knowledge regarding the alterations of gut microbiota (dysbiosis) and its correlation with human neurodegenerative and brain-related diseases, e.g., Alzheimer’s and Parkinson’s. This review underlines the importance of gut-derived metabolites and gut metabolic status as the main players in gut-brain crosstalk and their implications on the severity of neural conditions. Scientific evidence indicates that the administration of probiotic bacteria exerts beneficial and protective effects as reduced systemic inflammation, neuroinflammation, and inhibited neurodegeneration. The experimental results performed on animals, but also human clinical trials, show the importance of designing a novel microbiota-based probiotic dietary supplementation with the aim to prevent or ease the symptoms of Alzheimer’s and Parkinson’s diseases or other forms of dementia or neurodegeneration.

Background/Objectives: Advanced glycation end products (AGEs) and oxidative stress increase with aging and are implicated in Alzheimer’s disease (AD). We developed an anti-glycation blend using LC-MS-based screening and assessed its effects on oxidative and glycation-related biomarkers in humans. Methods: Twelve candidate compounds were screened in a BSA–glucose model using LC-MS peptide mapping to quantify lysine glycation and rank inhibitory activity. The top candidates were combined into a three-compound blend (quercetin, rutin, genistein). In a randomized, double-blind, placebo-controlled 3-month trial, older healthy adults (n = 30) and individuals with AD (n = 30) received anti-AGE blend (n = 15 in older group and n = 15 in AD group) or placebo (n = 15 in older group and n = 15 in AD group). Serum malondialdehyde and urinary Nε-(carboxymethyl)lysine were measured pre–post intervention. Pre/post and between-arm comparisons within each population were performed using REML ANOVA with Tukey post hoc tests. Serum MDA (malondialdehyde) and urinary CML (Nε-(carboxymethyl)lysine) were prespecified biomarker outcomes and are reported here as co-primary biomarker endpoints. No formal a priori sample size calculation was performed; the study size was feasibility-based. Results: LC-MS screening identified genistein, quercetin, and rutin as the most consistent inhibitors of glucose-driven BSA glycation. In older healthy adults, serum MDA decreased after anti-AGE supplementation (p < 0.001) and differed from the placebo (p < 0.01), while no change was observed within the placebo group (ns). In the AD cohort, MDA did not change significantly from baseline within either arm (ns), but post-intervention MDA was lower in anti-AGE than in the placebo (p < 0.05). Urinary CML was unchanged in older healthy adults (ns in both arms), whereas in AD, it decreased after anti-AGE supplementation (p < 0.01) and differed from the placebo (p < 0.05). Conclusions: A screening-guided anti-glycation blend supplementation was associated with changes in selected biomarkers in humans: MDA decreased across cohorts, while CML decreased selectively in AD. Larger trials with extended biomarker panels and LC–MS/MS confirmation are warranted.

Background: The proper functioning of the nervous system determines the homeostasis of the entire body. There are many known approaches designed to positively stimulate the functions of the central nervous system by applying various plants and fungal extracts, but their course of action is poorly understood. Hericium erinaceus and Ganoderma lucidum are examples of fungi with medicinal properties and with a positive health-promoting effect. Therefore, the aim of our study was to evaluate the effect of H. erinaceus or G. lucidum M-CFS with their active metabolites alone and/or in co-treatment with CAY10464 [antagonist of aryl hydrocarbon receptor (AhR)] on the metabolic parameters, cell cycle, and selected protein expression. Methods: The study was based on the use of the resazurin reduction assay, flow cytometry analyses, and Western blotting in the mouse hippocampal neuronal cell line (HT-22) in vitro. Results: The obtained results proved no cytotoxicity of the tested metabolites towards the HT-22 cells in the concentration range of 2.5% − 10% of culture medium. The cells treated with the tested compounds were characterized by an increase in the protein expression of SQSTM/p62, PCNA, c-SRC, SOD1, AhR, Beclin 1, and ERK1/2. Moreover, a significant role of AhR in the mechanism of action of the tested metabolites was observed at the protein expression level. Conclusion: The observed increase in the proliferation-related markers in the HT-22 cells proves the beneficial protective potential of these M-CFSs. Given the findings, we speculate their positive impact on the cognitive functions in the central nervous system. Clinical trial registration date: Not applicable. Clinical trial number: Not applicable. Graphical