图1 gp120tg小鼠与WT型小鼠肠道菌群多样性及菌属丰度差异分析

Fig.1 Analysis of diversity and abundance of intestinal microbiota in gp120tg mice and WT mice. A: Simpson's diversity index of the microbiome in gp120tg mice (n=14) and WT mice (n=20). B: Principal coordinate analysis (PCoA) using unweighted UniFrac distance in gp120tg mice (n=14) and WT mice (n=20). C: Heatmap for comparison of microbiota abundance at the genus level between 12-month-old gp120tg mice (n=4) and WT mice (n=6). D: Abundance of Akkermansia genus in different groups of mice (n=3-4). *P<0.05, ***P < 0.001.

图2 gp120tg小鼠与WT型小鼠肠屏障相关指标表达情况

Fig.2 Expression of intestinal barrier-related indexes in gp120tg mice and WT mice. A: PAS staining of mouse colon tissues. B: Quantification of goblet cell loss of mouse colon tissues (n=3-4). C: ELISA validation of LPS levels in mouse serum (n=5). D-F: Quantification of INF-γ, occludin and ZO-1 expression levels in the mouse colon (n=3). **P<0.01, ***P<0.001.

图3 gp120tg小鼠与WT型小鼠炎症及免疫反应相关指标表达情况

Fig.3 Expression of inflammation- and immune response-related indexes in gp120tg mice and WT mice. A: Hematoxylin-chromotrope staining of mouse colon tissues (scale bar=50 μm). B: MBP staining of the mouse colon tissues (MBP-positive areas are brown or reddish-brown; scale bar=50 μm). C: Quantification of eosinophils in the mouse colon tissues (n=3 or 4). D: Mean gray value of MBP in the colon (n=3). E, F: Quantification of IL-10 and TNF-α expression levels in the mouse colon (n=3). G: ELISA validation of IL-1β levels in the mouse colon (n=4). *P<0.05, **P<0.01, ***P<0.001.

图4 A.muciniphila灌胃对12月龄gp120tg小鼠与WT型小鼠肠屏障相关指标表达情况的影响

Fig.4 Effects of oral gavage of A.muciniphila on expression of gut barrier-related indexes in the colon of 12-month-old gp120tg mice and WT mice. A: PAS staining of mouse colon tissues (scale bar=50 μm). B: Quantification of goblet cell loss in mouse colon tissues (n=3 or 4). C-E: Quantification of INF-γ, occludin and ZO-1 expression levels in mouse colon (n=3). Mice were gavaged once a day with A. muciniphila (2×108 CFU per mouse) for 6 weeks. F: Changes of body weight of the mice during oral gavage of A.muciniphila. **P<0.01, ***P< 0.001.

图5 A.muciniphila灌胃对12月龄gp120tg小鼠与WT型小鼠炎症及免疫反应相关指标表达情况的影响

Fig.5 Effects of oral gavage of A.muciniphila onexpression of inflammation- and immune response-related indexes in 12-month-old gp120tg mice and WT mice. A: Hematoxylin-chromotrope staining of mouse colon tissues. B: MBP staining in the mouse colon tissues. C: Quantification of eosinophils in the mouse colon tissues (n=3 or 4). D: Mean gray value of MBP in the colon (n=3). E, F: Quantification of IL-10 and TNF-α expression levels in mouse colon (n=3). G: ELISA validation of IL-1β levels in mouse colon (n=3 or 4). *P<0.05, **P<0.01, ***P<0.001.

图6 A.muciniphila灌胃对12月龄gp120tg小鼠与WT型小鼠学习及空间记忆能力的影响

Fig.6 Effects of oral gavage of A.muciniphila on learning and spatial memory abilities of 12-month-old gp120tg mice and WT mice. A: Movement trajectory diagrams of the mice in the spatial exploration experiments (n=6). B: Movement time in each quadrant in the spatial exploration experiments (n=6). C: Movement distance in each quadrant in the spatial exploration experiments (n=6). D: Crossing times of the platform in the spatial exploration experiments (n=6). E: Swimming speed of the mice in the spatial exploration experiments (n=6). F: Total distance moved of the mice in the spatial exploration experiments (n=6). *P<0.05, **P<0.01.

图7 A.muciniphila灌胃对12月龄gp120tg小鼠与WT型小鼠神经元的影响

Fig.7 Effects of A.muciniphila gavage on neuronal damage in 12-month-old gp120tg mice and WT mice. A: Immunofluorescence showing the distribution of NeuN in the mouse hippocampus (scale bar=100 μm). B: Mean gray value of NeuN in the mouse hippocampus (n=3). C: Immunofluorescence showing the distribution of NeuN in the mouse cortex (scale bar=100 μm). D: Mean gray value of NeuN in the mouse cortex (n=3). *P<0.05, **P<0.01.