Fig. 5: Direct introduction of Oscillibacter alleviates Aβ-related AD pathologies in 5xFAD mice. | Nature Communications

Fig. 5: Direct introduction of Oscillibacter alleviates Aβ-related AD pathologies in 5xFAD mice.

From: Gut microbiota-dependent 24-hydroxycholesterol metabolism contributes to capsaicin-induced amelioration of Alzheimer’s disease-like pathology in mice

Fig. 5: Direct introduction of Oscillibacter alleviates Aβ-related AD pathologies in 5xFAD mice.

a Featured enrichment of gut microbes at genus level, including Oscillibacter, in healthy individuals versus AD patients recorded in GMrepo v2 database. Linear discriminant analysis (LDA) scores were acquired using LEfSe analysis. b AD patients showed significantly decreased Oscillibacter abundance compared with healthy group. n = 15,780 (healthy) or 218 (AD). Data are presented as box and whiskers, Tukey. Two‑sided Mann–Whitney U test. c Experimental procedures of Oscillibacter isolation from gut contents of Cap-treated 5xFAD mice. d Isolated Oscillibacter (Osc.) showed high expression levels of Osc.-specific 16S rRNA, ismA and CgT homologous genes relative to the level of pan bacterial 16S rRNA. n = 5 dishes per group. Culture medium and E. coli were used as negative control. J115 was used as positive control. Data are presented as box and whiskers, min-max. e 24-HC level in the culture medium of Oscillibacter was upregulated following cholesterol treatment, and further increased under Cap co-treatment. n = 5 dishes per group. Data are presented as box and whiskers, min-max. One-way ANOVA followed by Tukey’s multiple comparisons tests. f Experimental scheme of medium and Oscillibacter delivery in 5xFAD mice. g–j Direct Oscillibacter grafting decreased Aβ plaques density (h), decreased the soma volume (i) and increased cell processes branching complexity (j) of microglia in the hippocampal CA1 of 5xFAD mice compared with medium (M.). Arrows in presentative images (g) indicate microglia showed in reconstructed images (lower panels). Crosses indicate individual cells and circles indicate mean values of individual mouse (i). Bands indicate SD (j). n = 40 cells from 8 mice in each group. Data are presented as box and whiskers, min-max (h, k), or mean ± SD (i, j). Two‑sided unpaired t tests (h, i) or two-way ANOVA (j). k Oscillibacter downregulated pro-inflammatory levels in the hippocampal tissue. n = 8 mice in each group. Data were normalized to the mean value of medium group. Data are presented as box and whiskers, min-max. Two-way ANOVA followed by Tukey’s multiple comparisons tests. l,m Oscillibacter improved object-place recognition of 5xFAD mice. n = 8 mice in each group. Data are presented as box and whiskers, min-max. Two‑sided unpaired t test. Oscillibacter improved spatial learning (n) and memory (o) of 5xFAD mice in the Morris-water maze test. Cyan areas indicate the target quadrant in water maze (o). n = 8 mice in each group. Data are presented as mean ± SD (n), or box and whiskers, min-max (o). Two-way ANOVA (n) or two‑sided unpaired t test (o). Source data are provided as a Source Data file. Illustrative components in panels (c and f) are created in BioRender. Zheng, J. (2026) https://BioRender.com/c9dsmfb.

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