Bifidobacterium breve MCC1274 Supplementation Increased the Plasma Levels of Metabolites with Potential Anti-Oxidative Activity in APP Knock-In Mice

Abstract

Background: We previously reported the effects of a probiotic strain, Bifidobacterium breve MCC1274, in improving cognitive function in preclinical and clinical studies. Recently, we demonstrated that supplementation of this strain led to decreased amyloid-β production, attenuated microglial activation, and suppressed inflammation reaction in the brain of APP knock-in (App NL - G - F ) mice. Objective: In this study, we investigated the plasma metabolites to reveal the mechanism of action of this probiotic strain in this Alzheimer’s disease (AD)-like model. Methods: Three-month-old mice were orally supplemented with B. breve MCC1274 or saline for four months and their plasma metabolites were comprehensively analyzed using CE-FTMS and LC-TOFMS. Results: Principal component analysis showed a significant difference in the plasma metabolites between the probiotic and control groups (PERMANOVA, p = 0.03). The levels of soy isoflavones (e.g., genistein) and indole derivatives of tryptophan (e.g., 5-methoxyindoleacetic acid), metabolites with potent anti-oxidative activities were significantly increased in the probiotic group. Moreover, there were increased levels of glutathione-related metabolites (e.g., glutathione (GSSG)_divalent, ophthalmic acid) and TCA cycle-related metabolites (e.g., 2-Oxoglutaric acid, succinic acid levels) in the probiotic group. Similar alternations were observed in the wild-type mice by the probiotic supplementation. Conclusion: These results suggest that the supplementation of B. breve MCC1274 enhanced the bioavailability of potential anti-oxidative metabolites from the gut and addressed critical gaps in our understanding of the gut-brain axis underlying the mechanisms of the probiotic action of this strain in the improvement of cognitive function.

Gut-Modulating Agents and Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives

“…These changes were associated with increased regulation of gut microbiota composition and improvement in intestinal barrier function [ 89 ], highlighting the therapeutic potential of GBA modulation. Another study similarly reported Bifidobacterium breve supplementation in amyloid beta precursor protein (APP) knock-in mice increased the bioavailability of anti-oxidative metabolites, which improved cognitive function [ 90 ]. Huang et al [ 91 ] demonstrated that the use of Lactobacillus plantarum can delay AD progression by regulating gliosis and tau hyperphosphorylation following a reduction in propionic acid levels.…”

Postbiotic production: harnessing the power of microbial metabolites for health applications

“…A recent study, for example, looked at the postbiotic potential of L. plantarum metabolites, finding that they can boost the production of short-chain fatty acids, which are known to support intestinal epithelial integrity ( Markowiak-Kopeć and Śliżewska, 2020 ). Furthermore, research on metabolites produced from B. breve exhibited potential in controlling glucose metabolism ( Ohno et al, 2022 ). Integrating postbiotics into functional foods and beverages, such as yogurt, fermented drinks, or even snacks, is an innovative strategy for delivering these health advantages in a practical and pleasant way ( Thorakkattu et al, 2022 ).…”

Probiotic Bifidobacterium breve MCC1274 Protects against Oxidative Stress and Neuronal Lipid Droplet Formation via PLIN4 Gene Regulation

“…Furthermore, treating APPKI mice (AppNL-G-F) with the same probiotic reduced amyloid plaque deposition, increased alpha-secretase expression, and decreased microglial cell activation [ 26 ]. Plasma metabolomics analysis of these mice indicated that MCC1274 consumption increased the levels of several metabolites with known activity against oxidative stress, as well as metabolites related to the mitochondrial TCA cycle, although the specific metabolite(s) responsible for these effects were not identified [ 27 ]. In the present study, we asked whether other metabolites generated by this probiotic prevent the inflammation-derived oxidative stress and lipid droplet formation that occur in MCI and Alzheimer’s disease by controlling perilipin gene expression.…”