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Chronic Bifidobacterium pseudocatenulatum administration induces intestinal dysfunction and moyamoya disease-relevant vasculopathy. (A) Schematic of the experimental design for B. pseudocatenulatum administration in C57BL/6J mice. (B) Representative hematoxylin–eosin-stained images of colon tissue (left) and quantification of histological scores (right) from PBS control mice and B. pseudocatenulatum mice at 24 wpfg. Scale bar, 20 μm. Data were shown as mean ± standard deviation with p values (Wilcoxon rank-sum test). n = 6 mice/group. (C) Representative immunohistochemical images (left) and quantification of % area occupied for ZO-1 (right) in colon tissue from PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 20 μm. Data were shown as mean ± standard deviation with p values (Mann–Whitney U test). n = 6 mice/group. (D – G) ELISA analysis of fecal CALP and LF (D), fecal histamine and serotonin (E), serum histamine and serotonin (F), and serum IL-1β and TNF-α (G) between PBS-treated and B. pseudocatenulatum -treated mice at 4, 12, and 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (two-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (H) ELISA analysis of serum VEGF and <t>eNOS</t> levels between PBS-treated and B. pseudocatenulatum -treated mice at 4, 12, and 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (two-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (I) ELISA analysis of cerebral VEGF and eNOS levels between PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (J) Representative immunofluorescence images of VEGF (green) and CD31 (red) in brain sections (left), and quantification of VEGF area % (right) between PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (K) Representative Weigert's resorcin-fuchsin-stained images of common carotid arteries (CCAs) (left) and quantification of internal elastic lamina (IEL) thickness (right) from PBS control and B. pseudocatenulatum mice at 24 wpfg. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (L) Representative immunofluorescence images of CD31 staining (left) and quantification of % area occupied with CD31 (right) in cortex, striatum, hippocampus, and substantia nigra from PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 50 μm. All box-and-whisker plots depict the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. B. pseudocatenulatum , Bifidobacterium pseudocatenulatum ; HE, hematoxylin and eosin; <t>CALP,</t> <t>calprotectin;</t> LF, lactoferrin; wpfg, weeks post-first gavage; VEGF, vascular endothelial growth factor; eNOS, endothelial nitric oxide synthase.
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Chronic Bifidobacterium pseudocatenulatum administration induces intestinal dysfunction and moyamoya disease-relevant vasculopathy. (A) Schematic of the experimental design for B. pseudocatenulatum administration in C57BL/6J mice. (B) Representative hematoxylin–eosin-stained images of colon tissue (left) and quantification of histological scores (right) from PBS control mice and B. pseudocatenulatum mice at 24 wpfg. Scale bar, 20 μm. Data were shown as mean ± standard deviation with p values (Wilcoxon rank-sum test). n = 6 mice/group. (C) Representative immunohistochemical images (left) and quantification of % area occupied for ZO-1 (right) in colon tissue from PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 20 μm. Data were shown as mean ± standard deviation with p values (Mann–Whitney U test). n = 6 mice/group. (D – G) ELISA analysis of fecal CALP and LF (D), fecal histamine and serotonin (E), serum histamine and serotonin (F), and serum IL-1β and TNF-α (G) between PBS-treated and B. pseudocatenulatum -treated mice at 4, 12, and 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (two-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (H) ELISA analysis of serum VEGF and <t>eNOS</t> levels between PBS-treated and B. pseudocatenulatum -treated mice at 4, 12, and 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (two-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (I) ELISA analysis of cerebral VEGF and eNOS levels between PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (J) Representative immunofluorescence images of VEGF (green) and CD31 (red) in brain sections (left), and quantification of VEGF area % (right) between PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (K) Representative Weigert's resorcin-fuchsin-stained images of common carotid arteries (CCAs) (left) and quantification of internal elastic lamina (IEL) thickness (right) from PBS control and B. pseudocatenulatum mice at 24 wpfg. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (L) Representative immunofluorescence images of CD31 staining (left) and quantification of % area occupied with CD31 (right) in cortex, striatum, hippocampus, and substantia nigra from PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 50 μm. All box-and-whisker plots depict the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. B. pseudocatenulatum , Bifidobacterium pseudocatenulatum ; HE, hematoxylin and eosin; <t>CALP,</t> <t>calprotectin;</t> LF, lactoferrin; wpfg, weeks post-first gavage; VEGF, vascular endothelial growth factor; eNOS, endothelial nitric oxide synthase.
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Chronic Bifidobacterium pseudocatenulatum administration induces intestinal dysfunction and moyamoya disease-relevant vasculopathy. (A) Schematic of the experimental design for B. pseudocatenulatum administration in C57BL/6J mice. (B) Representative hematoxylin–eosin-stained images of colon tissue (left) and quantification of histological scores (right) from PBS control mice and B. pseudocatenulatum mice at 24 wpfg. Scale bar, 20 μm. Data were shown as mean ± standard deviation with p values (Wilcoxon rank-sum test). n = 6 mice/group. (C) Representative immunohistochemical images (left) and quantification of % area occupied for ZO-1 (right) in colon tissue from PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 20 μm. Data were shown as mean ± standard deviation with p values (Mann–Whitney U test). n = 6 mice/group. (D – G) ELISA analysis of fecal CALP and LF (D), fecal histamine and serotonin (E), serum histamine and serotonin (F), and serum IL-1β and TNF-α (G) between PBS-treated and B. pseudocatenulatum -treated mice at 4, 12, and 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (two-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (H) ELISA analysis of serum VEGF and <t>eNOS</t> levels between PBS-treated and B. pseudocatenulatum -treated mice at 4, 12, and 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (two-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (I) ELISA analysis of cerebral VEGF and eNOS levels between PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (J) Representative immunofluorescence images of VEGF (green) and CD31 (red) in brain sections (left), and quantification of VEGF area % (right) between PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (K) Representative Weigert's resorcin-fuchsin-stained images of common carotid arteries (CCAs) (left) and quantification of internal elastic lamina (IEL) thickness (right) from PBS control and B. pseudocatenulatum mice at 24 wpfg. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (L) Representative immunofluorescence images of CD31 staining (left) and quantification of % area occupied with CD31 (right) in cortex, striatum, hippocampus, and substantia nigra from PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 50 μm. All box-and-whisker plots depict the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. B. pseudocatenulatum , Bifidobacterium pseudocatenulatum ; HE, hematoxylin and eosin; <t>CALP,</t> <t>calprotectin;</t> LF, lactoferrin; wpfg, weeks post-first gavage; VEGF, vascular endothelial growth factor; eNOS, endothelial nitric oxide synthase.
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Chronic Bifidobacterium pseudocatenulatum administration induces intestinal dysfunction and moyamoya disease-relevant vasculopathy. (A) Schematic of the experimental design for B. pseudocatenulatum administration in C57BL/6J mice. (B) Representative hematoxylin–eosin-stained images of colon tissue (left) and quantification of histological scores (right) from PBS control mice and B. pseudocatenulatum mice at 24 wpfg. Scale bar, 20 μm. Data were shown as mean ± standard deviation with p values (Wilcoxon rank-sum test). n = 6 mice/group. (C) Representative immunohistochemical images (left) and quantification of % area occupied for ZO-1 (right) in colon tissue from PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 20 μm. Data were shown as mean ± standard deviation with p values (Mann–Whitney U test). n = 6 mice/group. (D – G) ELISA analysis of fecal CALP and LF (D), fecal histamine and serotonin (E), serum histamine and serotonin (F), and serum IL-1β and TNF-α (G) between PBS-treated and B. pseudocatenulatum -treated mice at 4, 12, and 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (two-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (H) ELISA analysis of serum VEGF and eNOS levels between PBS-treated and B. pseudocatenulatum -treated mice at 4, 12, and 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (two-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (I) ELISA analysis of cerebral VEGF and eNOS levels between PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (J) Representative immunofluorescence images of VEGF (green) and CD31 (red) in brain sections (left), and quantification of VEGF area % (right) between PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (K) Representative Weigert's resorcin-fuchsin-stained images of common carotid arteries (CCAs) (left) and quantification of internal elastic lamina (IEL) thickness (right) from PBS control and B. pseudocatenulatum mice at 24 wpfg. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (L) Representative immunofluorescence images of CD31 staining (left) and quantification of % area occupied with CD31 (right) in cortex, striatum, hippocampus, and substantia nigra from PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 50 μm. All box-and-whisker plots depict the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. B. pseudocatenulatum , Bifidobacterium pseudocatenulatum ; HE, hematoxylin and eosin; CALP, calprotectin; LF, lactoferrin; wpfg, weeks post-first gavage; VEGF, vascular endothelial growth factor; eNOS, endothelial nitric oxide synthase.

Journal: Genes & Diseases

Article Title: Gut microbial histamine and serotonin promote cerebrovascular angiogenesis: Evidence from moyamoya disease

doi: 10.1016/j.gendis.2026.102306

Figure Lengend Snippet: Chronic Bifidobacterium pseudocatenulatum administration induces intestinal dysfunction and moyamoya disease-relevant vasculopathy. (A) Schematic of the experimental design for B. pseudocatenulatum administration in C57BL/6J mice. (B) Representative hematoxylin–eosin-stained images of colon tissue (left) and quantification of histological scores (right) from PBS control mice and B. pseudocatenulatum mice at 24 wpfg. Scale bar, 20 μm. Data were shown as mean ± standard deviation with p values (Wilcoxon rank-sum test). n = 6 mice/group. (C) Representative immunohistochemical images (left) and quantification of % area occupied for ZO-1 (right) in colon tissue from PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 20 μm. Data were shown as mean ± standard deviation with p values (Mann–Whitney U test). n = 6 mice/group. (D – G) ELISA analysis of fecal CALP and LF (D), fecal histamine and serotonin (E), serum histamine and serotonin (F), and serum IL-1β and TNF-α (G) between PBS-treated and B. pseudocatenulatum -treated mice at 4, 12, and 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (two-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (H) ELISA analysis of serum VEGF and eNOS levels between PBS-treated and B. pseudocatenulatum -treated mice at 4, 12, and 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (two-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (I) ELISA analysis of cerebral VEGF and eNOS levels between PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. All box-and-whisker plots depict the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (J) Representative immunofluorescence images of VEGF (green) and CD31 (red) in brain sections (left), and quantification of VEGF area % (right) between PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (K) Representative Weigert's resorcin-fuchsin-stained images of common carotid arteries (CCAs) (left) and quantification of internal elastic lamina (IEL) thickness (right) from PBS control and B. pseudocatenulatum mice at 24 wpfg. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. (L) Representative immunofluorescence images of CD31 staining (left) and quantification of % area occupied with CD31 (right) in cortex, striatum, hippocampus, and substantia nigra from PBS-treated and B. pseudocatenulatum -treated mice at 24 wpfg. Scale bar, 50 μm. All box-and-whisker plots depict the median, quartiles, and range (Mann–Whitney U test). n = 6 mice/group. B. pseudocatenulatum , Bifidobacterium pseudocatenulatum ; HE, hematoxylin and eosin; CALP, calprotectin; LF, lactoferrin; wpfg, weeks post-first gavage; VEGF, vascular endothelial growth factor; eNOS, endothelial nitric oxide synthase.

Article Snippet: The calprotectin (CALP) and lactoferrin (LF), serotonin, histamine, IL-1β, TNF-α, VEGF, and eNOS in the mouse model were determined using mouse ELISA kits (E-EL-M1143, E-EL-M0746, E-EL-0033, E-EL-0032, E-EL-M0037, E-EL-M3063, E-EL-M1292, and E-EL-M0456 (Elabscience Biotechnology Co., Ltd., China)).

Techniques: Staining, Tissue, Control, Standard Deviation, Immunohistochemical staining, MANN-WHITNEY, Enzyme-linked Immunosorbent Assay, Analysis, Whisker Assay, Immunofluorescence

Serotonin and histamine trigger vascular remodeling. (A) Schematic of the experimental design for intraperitoneal serotonin or histamine injections. (B) ELISA analysis of serum VEGF and eNOS levels in PBS-injected, serotonin-injected, and histamine-injected mice at 12 weeks post-injection. All box-and-whisker plots depict the median, quartiles, and range (one-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (C) ELISA analysis of cerebral VEGF and eNOS levels in PBS-injected, serotonin-injected, and histamine-injected mice. All box-and-whisker plots depict the median, quartiles, and range (one-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (D) Representative immunofluorescence images (left) of VEGF (green) and CD31 (red) in brain sections, and quantification of VEGF fluorescence area % (right), among PBS-injected, serotonin-injected, and histamine-injected mice. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (one-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (E) Representative Weigert's resorcin-fuchsin-stained images of common carotid arteries (CCAs) (up) and quantification of internal elastic lamina (IEL) thickness (down) from PBS-injected, serotonin-injected, and histamine-injected mice. Scale bar, 20 μm. The box-and-whisker plot depicts the median, quartiles, and range (one-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (F) Representative immunofluorescence images of CD31 staining in cortex, striatum, hippocampus, and substantia nigra (up) and quantification of % area occupied with CD31 (down) in brain sections from PBS-injected, serotonin-injected, and histamine-injected mice. Scale bar, 50 μm. All box-and-whisker plots depict the median, quartiles, and range (one-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. VEGF, vascular endothelial growth factor; eNOS, endothelial nitric oxide synthase.

Journal: Genes & Diseases

Article Title: Gut microbial histamine and serotonin promote cerebrovascular angiogenesis: Evidence from moyamoya disease

doi: 10.1016/j.gendis.2026.102306

Figure Lengend Snippet: Serotonin and histamine trigger vascular remodeling. (A) Schematic of the experimental design for intraperitoneal serotonin or histamine injections. (B) ELISA analysis of serum VEGF and eNOS levels in PBS-injected, serotonin-injected, and histamine-injected mice at 12 weeks post-injection. All box-and-whisker plots depict the median, quartiles, and range (one-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (C) ELISA analysis of cerebral VEGF and eNOS levels in PBS-injected, serotonin-injected, and histamine-injected mice. All box-and-whisker plots depict the median, quartiles, and range (one-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (D) Representative immunofluorescence images (left) of VEGF (green) and CD31 (red) in brain sections, and quantification of VEGF fluorescence area % (right), among PBS-injected, serotonin-injected, and histamine-injected mice. Scale bar, 10 μm. The box-and-whisker plot depicts the median, quartiles, and range (one-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (E) Representative Weigert's resorcin-fuchsin-stained images of common carotid arteries (CCAs) (up) and quantification of internal elastic lamina (IEL) thickness (down) from PBS-injected, serotonin-injected, and histamine-injected mice. Scale bar, 20 μm. The box-and-whisker plot depicts the median, quartiles, and range (one-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. (F) Representative immunofluorescence images of CD31 staining in cortex, striatum, hippocampus, and substantia nigra (up) and quantification of % area occupied with CD31 (down) in brain sections from PBS-injected, serotonin-injected, and histamine-injected mice. Scale bar, 50 μm. All box-and-whisker plots depict the median, quartiles, and range (one-way ANOVA with Tukey's multiple comparisons test). n = 6 mice/group. VEGF, vascular endothelial growth factor; eNOS, endothelial nitric oxide synthase.

Article Snippet: The calprotectin (CALP) and lactoferrin (LF), serotonin, histamine, IL-1β, TNF-α, VEGF, and eNOS in the mouse model were determined using mouse ELISA kits (E-EL-M1143, E-EL-M0746, E-EL-0033, E-EL-0032, E-EL-M0037, E-EL-M3063, E-EL-M1292, and E-EL-M0456 (Elabscience Biotechnology Co., Ltd., China)).

Techniques: Enzyme-linked Immunosorbent Assay, Analysis, Injection, Whisker Assay, Immunofluorescence, Fluorescence, Staining