Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease
Parkinson’s disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether t...
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MDPI AG
2023-02-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/4/930 |
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| author | Tong-Tong Guo Zheng Zhang Yan Sun Rui-Yang Zhu Fei-Xia Wang Lian-Ju Ma Lin Jiang Han-Deng Liu |
| author_facet | Tong-Tong Guo Zheng Zhang Yan Sun Rui-Yang Zhu Fei-Xia Wang Lian-Ju Ma Lin Jiang Han-Deng Liu |
| author_sort | Tong-Tong Guo |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier’s disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut–brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut–brain axis inflammation. |
| first_indexed | 2024-03-11T08:18:55Z |
| format | Article |
| id | doaj.art-62c30faabce440fd9769ed84f9ea1f89 |
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| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T08:18:55Z |
| publishDate | 2023-02-01 |
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| series | Nutrients |
| spelling | doaj.art-62c30faabce440fd9769ed84f9ea1f892023-11-16T22:30:54ZengMDPI AGNutrients2072-66432023-02-0115493010.3390/nu15040930Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s DiseaseTong-Tong Guo0Zheng Zhang1Yan Sun2Rui-Yang Zhu3Fei-Xia Wang4Lian-Ju Ma5Lin Jiang6Han-Deng Liu7Laboratory of Tissue and Cell Biology, Experimental Teaching Center, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, ChinaLaboratory of Tissue and Cell Biology, Experimental Teaching Center, Chongqing Medical University, Chongqing 400016, ChinaLaboratory of Tissue and Cell Biology, Experimental Teaching Center, Chongqing Medical University, Chongqing 400016, ChinaLaboratory of Tissue and Cell Biology, Experimental Teaching Center, Chongqing Medical University, Chongqing 400016, ChinaLaboratory of Tissue and Cell Biology, Experimental Teaching Center, Chongqing Medical University, Chongqing 400016, ChinaParkinson’s disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier’s disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut–brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut–brain axis inflammation.https://www.mdpi.com/2072-6643/15/4/930sodium butyratemicrobiome–gut–brain axisneuroinflammationgut microbial dysbiosisParkinson’s disease |
| spellingShingle | Tong-Tong Guo Zheng Zhang Yan Sun Rui-Yang Zhu Fei-Xia Wang Lian-Ju Ma Lin Jiang Han-Deng Liu Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease Nutrients sodium butyrate microbiome–gut–brain axis neuroinflammation gut microbial dysbiosis Parkinson’s disease |
| title | Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease |
| title_full | Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease |
| title_fullStr | Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease |
| title_full_unstemmed | Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease |
| title_short | Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease |
| title_sort | neuroprotective effects of sodium butyrate by restoring gut microbiota and inhibiting tlr4 signaling in mice with mptp induced parkinson s disease |
| topic | sodium butyrate microbiome–gut–brain axis neuroinflammation gut microbial dysbiosis Parkinson’s disease |
| url | https://www.mdpi.com/2072-6643/15/4/930 |
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