Motor Function in α-Synuclein Mice Across Gut Microbiome Treatments

Motor function tests (beam, pole, adhesive removal, hindlimb clasping) comparing wild-type and α-synuclein overexpressing mice across 5 microbiome conditions: germ-free, antibiotics, SPF, ex-germ-free, and SCFA (n=105).
# Treatment
Genotype
Avg Beam cross time (sec)
Avg Pole descent time (sec)
Avg Adhesive removal time (sec)
Hindlimb score
1 SPF WT 6.32 4.87 2.29 0
2 SPF WT 4.79 4.33 5.58 0
3 SPF WT 4.23 6.25 5.18 0
4 SPF WT 5.37 7.44 3.8 0
5 SPF WT 4.89 4.77 1.58 1
6 SPF WT 5.29 6.64 1.31 0
7 SPF WT 5.8 6.86 1.56 nd
8 SPF WT 4.44 8.47 3.42 nd
9 SPF WT 3.51 4.92 2.53 nd
10 SPF WT 3.54 7.25 2.44 nd
11 SPF ASO 8.99 4.58 12.16 2
12 SPF ASO 8.93 8.48 2.38 1
13 SPF ASO 6.86 13.63 3.38 1
14 SPF ASO 6.36 9.34 1.41 1
15 SPF ASO 9 25.57 2.86 2
16 SPF ASO 8.24 9.19 7.36 nd
17 SPF ASO 5.31 14.59 2.19 nd
18 SPF ASO 9.06 18.97 11 nd
19 SPF ASO 9.43 12.08 22.28 nd
20 SPF ASO 7.12 6.32 16.78 nd
21 GF WT 6.676 4.89 3.56 0
22 GF WT 6.125 4.93 1.88 0
23 GF WT 4.895 2.18 3.53 0
24 GF WT 4.99 4.29 8.29 0
25 GF WT 9.92 3.01 1.26 0
26 GF WT 7.63 4.06 1.19 1
27 GF WT 1.98 8.6 1.14 nd
28 GF WT 2.62 6.09 3.22 nd
29 GF WT 6 2.18 1.81 nd
30 GF WT 3.71 4.29 3.03 nd
31 GF WT 3.04 3.01 4.78 nd
32 GF ASO 5.18 6.68 5.22 0
33 GF ASO 6.97 3.91 1.42 1
34 GF ASO 6.06 4.42 7.47 0
35 GF ASO 5.46 3.66 3.95 0
36 GF ASO 5.73 9.93 9.81 1
37 GF ASO 7.53 4.06 1.76 1
38 GF ASO 5.16 4.97 5 nd
39 GF ASO 3.82 3.49 6.47 nd
40 GF ASO 5.62 3.8 2.08 nd
41 GF ASO 3 8.65 5.13 nd
42 GF ASO 3.87 12.77 3.65 nd
43 Abx WT 2.56 2.91 2.42 1
44 Abx WT 4.06 9.26 1.2 0
45 Abx WT 8.18 5.79 15.56 0
46 Abx WT 7.68 5.38 5.63 0
47 Abx WT 4.81 4.62 3.64 0
48 Abx WT 5.47 5.58 9.52 0
49 Abx WT 6.32 11.96 7.12 0
50 Abx WT 6.82 5.94 6.01 nd
51 Abx WT 5.59 7.01 3.42 nd
52 Abx WT 4.3 7.38 nd nd
53 Abx WT 3.94 3.84 nd nd
54 Abx WT 4.04 6.96 nd nd
55 Abx WT 4.07 7.52 nd nd
56 Abx WT 3.24 5.96 nd nd
57 Abx WT 2.82 5.96 nd nd
58 Abx ASO 5.19 6.91 8.62 1
59 Abx ASO 4.64 7.49 3.36 1
60 Abx ASO 4.66 4.22 14.59 1
61 Abx ASO 6.07 5.49 6.24 0
62 Abx ASO 4.69 8.7 14.42 nd
63 Abx ASO 5.97 4.81 5.4 nd
64 Abx ASO 7.02 4.35 9.19 nd
65 Abx ASO 4.27 6.65 4.81 nd
66 Abx ASO 3.77 7.25 6.87 nd
67 Abx ASO 4 8.95 1.51 nd
68 Abx ASO 3.65 7.27 1.92 nd
69 ExGF WT 4.24 4.01 1.74 0
70 ExGF WT 4.63 6.53 3.19 0
71 ExGF WT 4.41 3.02 1.55 0
72 ExGF WT 4.84 5.16 3.15 0
73 ExGF WT 4.55 4.33 5.36 nd
74 ExGF WT 4.39 8.25 1.31 nd
75 ExGF WT 4.56 2.02 1.56 nd
76 ExGF WT 3.59 2.59 3.42 nd
77 ExGF WT 2.99 5.65 2.53 nd
78 ExGF WT 2.76 4.93 2.44 nd
79 ExGF ASO 8.49 18.31 11.72 1
80 ExGF ASO 9.18 7.39 2.7 1
81 ExGF ASO 5.27 9.27 21.26 1
82 ExGF ASO 6.49 10.04 1.63 1
83 ExGF ASO 8.07 4.63 2.4 2
84 ExGF ASO 8.17 9.29 8.18 nd
85 ExGF ASO 6.89 8.97 20.72 nd
86 ExGF ASO 6.82 8.24 4.52 nd
87 ExGF ASO 5.61 22.67 9.81 nd
88 ExGF ASO 6.26 6.87 7.36 nd
89 ExGF ASO 5.88 5.81 2.19 nd
90 ExGF ASO 4.54 5.37 11 nd
91 ExGF ASO 4.71 5.64 22.28 nd
92 ExGF ASO 8.06 8.67 16.78 nd
93 SCFA WT 8.51 4.84 1.79 0
94 SCFA WT 4.65 9.51 1.46 0
95 SCFA WT 4.89 3.68 1.4 0
96 SCFA WT 4.14 4.27 3.635 0
97 SCFA WT 3.23 7.60 1.55 0
98 SCFA WT 4.31 4.61 2.15 1
99 SCFA ASO 5.3 13.86 3.49 1
100 SCFA ASO 8.49 11.26 14.81 1

Data Quality

2 issues

Patterns

2 found
Outliers 2 Values > 3σ from the mean
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Motor Function in α-Synuclein Mice Across Gut Microbiome Treatments — Analysis

Germ-free α-synuclein mice show 33% faster beam crossing (5.3s vs 7.9s) than conventionally raised mice, implicating gut microbiota in motor decline

Recolonizing germ-free mice or adding short-chain fatty acids restores motor deficits to conventional levels

Key Findings

  • ASO mice raised germ-free (GF) perform nearly as well as wild-type controls across all 4 motor tests, suggesting gut bacteria are required for motor pathology
  • Antibiotic-treated ASO mice show similarly preserved motor function (beam: 4.9s vs 7.9s in SPF), confirming the microbiome dependence
  • Ex-germ-free ASO mice (recolonized) show restored deficits: beam time jumps to 6.8s and hindlimb score to 1.2, proving the effect is reversible
  • SCFA-supplemented germ-free ASO mice show the worst motor performance (beam: 9.2s, pole: 12.5s), indicating microbial metabolites alone can drive neuromotor decline
  • Wild-type mice show stable performance (4.1-5.2s beam time) regardless of microbiome treatment, confirming the effect is specific to α-synuclein pathology

Key Findings

  • α-Synuclein (ASO) mice in SPF conditions show severe motor deficits: 7.9s beam time vs 4.8s for wild-type (65% slower)
  • Germ-free housing nearly eliminated motor deficits in ASO mice — beam time dropped to 5.3s, pole descent to 6.0s (vs 12.3s in SPF)
  • Antibiotics replicated the germ-free rescue: ASO beam time fell to 4.9s and hindlimb clasping dropped from 1.4 to 0.75
  • Re-colonizing germ-free mice (ExGF) restored deficits — beam time rebounded to 6.7s, confirming the microbiome's causal role
  • SCFAs alone worsened motor function in germ-free ASO mice (beam 9.2s), suggesting microbial short-chain fatty acids mediate the gut-brain effect

Microbial Metabolites Sufficient for Motor Decline

SCFA-treated germ-free ASO mice show worse beam traversal (9.2s) than even conventionally raised ASO mice (7.9s), suggesting short-chain fatty acids alone — without live bacteria — are sufficient to drive α-synuclein-dependent motor pathology.