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Principal component evaluation (PCA) showed a clear difference in between the microbial communities of capsaicin-treated and vehicle-treated APP/PS1 mice (Figure 3A). Unique alpha-diversity indices, including Shannon (p = 0.0413), Simpson (p = 0.0295), Chao (p = 0.4616) and Ace (p = 0.3999), indicated that capsaicin considerably decreased gut bacterial alpha diversity, which was associated together with the antibacterial activity of capsaicin (Figure S1A). Comparing the relative abundances with the bacterial communities involving capsaicin-treated and vehicle-treated APP/PS1 mice, we discovered alterations inside the bacterial phylum levels (Figure 3B). The capsaicintreated APP/PS1 mice harbored a larger relative abundance of Verrucomicrobiota than vehicle-treated animals (p 0.0001). In addition, we also observed that capsaicin eating plan improved the relative abundance of bacterial genera, such as Akkermansia, Faecalibaculum, Unclassified_f_Atopobiaceae, Gordonibacter and decreased the relative abundance of bacterial genera, like Adlercreutzia, Peptococcaceae, Alistipes, Oscillibacter, Erysipelatoclostridium (Figure 3C). The abundance of phylum Verrucomicrobiota, genus Akkermansia, and species A. muciniphila (all of which comprise Gram-negative bacterial groups) in the APP/PS1_CP group considerably increased when compared with the APP/PS1_CTRL group (p = 0.0002) (Figure 3D). The results implied that capsaicin includes a profound impact on the composition of microbiota. Research have discovered that the relative abundance of A. muciniphila in APP/PS1 mice decreased with age [25]. Additionally, current proof suggests that supplementation having a. muciniphila of course lowered amyloid aggregation in the cerebral cortex and improved cognitive deficits and in AD mice [26]. Within the present study, the greater abundance of species A. muciniphila in APP/PS1_CP versus APP/PS1_CTRL animals is significant (Figure 3D), that is in agreement with previous data.IL-7 Protein Accession three.four. Capsaicin Upregulated Tryptophan Metabolism and Downregulated Lipid Metabolism in APP/PS1 Mice Serum metabolites hyperlink the microbiome to its host by regulating metabolism [27].IL-17A, Human (HEK293, His) Thus, serum metabolome processes were performed utilizing LC/MS-MS.PMID:28038441 The PCA evaluation showed that serum metabolic profiles in capsaicin-treated APP/PS1 mice have been significantly diverse from vehicle-treated APP/PS1 mice (Figure 4A). Forty-two metabolites have been specifically altered within the serum with the APP/PS1_CP group compared with the APP/PS1_CTRL group (Figure 4B).Nutrients 2023, 15, x FOR PEER Review Nutrients 2023, 15,7 7of 17 ofFigure two. Capsaicin reduces -amyloid plaques deposits of brain tissues in APP/PS1 mice (all groups: n = four). (A) Representative photos of brain tissues making use of Congo red staining in all mice (arrows label Figure two. Capsaicin reduces -amyloid plaques deposits of brain tissues in APP/PS1 mice (all A plaques). (B,C) represent the pictures ofof -amyloid plaques inside the hippocampus and cortex. groups: n = 4). (A) Representative deposits brain tissues making use of Congo red staining in all mice (arResults are imply SEM. The minimum significance value was considered as p 0.05. rows label A plaques). (B,C) represent the deposits of -amyloid plaques within the hippocampus andcortex. Results are imply SEM. The minimum significance worth was deemed as p 0.05.The altered metabolites have been involved in different metabolic pathways. Numerous preceding studies showed that short-chain fatty acids, bile acids, and tryptophan (Trp) metabolites would be the 3 most important metabolic p.