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Research article
Daryi Wang
Academia Sinica
Corresponding Author
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Background: Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. To date, the current pharmacological treatments for neuropathic pain are still unsatisfactory. The gut microbiota reportedly plays important roles in inducing neuropathic pain, so probiotics have also been used to treat it. However, the underlying questions around the interactions in and stability of the gut microbiota in a spared nerve injury-induced neuropathic pain model and the key microbes (i.e., the microbes that play critical roles) involved have not been answered. We collected 66 fecal samples over two weeks (three mice and 11 time points in spared nerve injury-induced neuropathic pain and Sham groups). The 16S rRNA gene was polymerase chain reaction amplified, sequenced on a MiSeq platform, and analyzed using a MOTHUR- UPARSE pipeline.
Results: Here we show that spared nerve injury-induced neuropathic pain alters gut microbial diversity in mice. We successfully constructed reliable microbial interaction networks using the Metagenomic Microbial Interaction Simulator (MetaMIS) and analyzed these networks based on 177,147 simulations. Interestingly, at a higher resolution, our results showed that spared nerve injury-induced neuropathic pain altered both the stability of the microbial community and the key microbes in a gut micro-ecosystem. Oscillospira, which was classified as a low-abundance and core microbe, was identified as the key microbe in the Sham group, whereas Staphylococcus, classified as a rare and non-core microbe, was identified as the key microbe in the spared nerve injury-induced neuropathic pain group.
Conclusions: In summary, our results provide novel experimental evidence that spared nerve injury-induced neuropathic pain reshapes gut microbial diversity, and alters the stability and key microbes in the gut.
Keywords
microbiota, next-generation sequencing, diversity, disturbance, chronic pain, interaction
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This is a list of supplementary files associated with this preprint. Click to download.
- SupplementarymaterialsDaryiWangrevised.docx
Supplemental Figure 1. Assessment of sufficient sequencing depth by rarefaction analyses. Individual rarefaction curves for each time-series sample from the Sham (blue) or SNI (red) group. Supplemental Figure 2: Multiple linear regression analyses for the final ranks of microbes and centrality. A) Sham group (p value < 0.001; R2=0.9167), B) SNI group (p value < 0.001; R2=0.8877). Supplemental Figure 3: Simplified microbial interaction networks that highlight the positive and negative interactions among key microbes or probiotics within the networks. A) Microbial interaction network in the Sham group with Oscillospira (26) at the center; B) Staphylococcus (53) in the SNI group; C) Lactobacillus (17) in the Sham group; D) Lactobacillus (17) in the SNI group; E) Bifidobacterium (48) in the Sham group; F) Bifidobacterium (48) in the SNI group. Supplemental Table 1. Differential relative abundance between the SNI group and Sham group (n=6) for each day at the genus level using DESeq2. pvalue = the average of the normalized counts, log2FoldChange = log2 fold change between the groups, lfcSE = standard error of the log2FoldChange estimate, stat = Wald statistic, pvalue = Wald test p-value, padj = Benjamini-Hochberg adjusted p-value. Supplemental Table 2.1. The ranks and values of each genus in the Sham group based on betweenness centrality, closeness centrality, and degree centrality. Supplemental Table 2.2. The ranks and values of each genus in the SNI group based on betweenness centrality, closeness centrality, and degree centrality.
- NC3RsARRIVEGuidelinesChecklist2014DaryiWang.docx
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View the published article at BMC Microbiology.
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Editorial decision: Accept
On 16 Sep, 2020
Editor assigned
On 15 Sep, 2020
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On 14 Sep, 2020
Editor invited
On 14 Sep, 2020
Version 2
Posted 04 Sep, 2020
No comments provided
Editorial decision: Minor revision
On 14 Sep, 2020
Reviewers invited
Invitations sent on 10 Sep, 2020
Editor assigned
On 02 Sep, 2020
Submission checks complete
On 01 Sep, 2020
Editor invited
On 01 Sep, 2020
No comments provided
Editorial decision: Major revision
On 04 Aug, 2020
Review #2 received
Received 01 Aug, 2020
Reviewer #2 agreed
On 07 Jul, 2020
Review #1 received
Received 06 Jul, 2020
Reviewers invited
Invitations sent on 22 Jun, 2020
Reviewer #1 agreed
On 22 Jun, 2020
First submitted
On 04 Jun, 2020
Editor assigned
On 04 Jun, 2020
Submission checks complete
On 03 Jun, 2020
Editor invited
On 03 Jun, 2020
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at BMC Microbiology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Daryi Wang
Academia Sinica
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Microbiology.
No community comments so far
Editorial decision: Accept
On 16 Sep, 2020
Editor assigned
On 15 Sep, 2020
Submission checks complete
On 14 Sep, 2020
Editor invited
On 14 Sep, 2020
Version 2
Posted 04 Sep, 2020
No comments provided
Editorial decision: Minor revision
On 14 Sep, 2020
Reviewers invited
Invitations sent on 10 Sep, 2020
Editor assigned
On 02 Sep, 2020
Submission checks complete
On 01 Sep, 2020
Editor invited
On 01 Sep, 2020
No comments provided
Editorial decision: Major revision
On 04 Aug, 2020
Review #2 received
Received 01 Aug, 2020
Reviewer #2 agreed
On 07 Jul, 2020
Review #1 received
Received 06 Jul, 2020
Reviewers invited
Invitations sent on 22 Jun, 2020
Reviewer #1 agreed
On 22 Jun, 2020
First submitted
On 04 Jun, 2020
Editor assigned
On 04 Jun, 2020
Submission checks complete
On 03 Jun, 2020
Editor invited
On 03 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Microbiology.
Background: Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. To date, the current pharmacological treatments for neuropathic pain are still unsatisfactory. The gut microbiota reportedly plays important roles in inducing neuropathic pain, so probiotics have also been used to treat it. However, the underlying questions around the interactions in and stability of the gut microbiota in a spared nerve injury-induced neuropathic pain model and the key microbes (i.e., the microbes that play critical roles) involved have not been answered. We collected 66 fecal samples over two weeks (three mice and 11 time points in spared nerve injury-induced neuropathic pain and Sham groups). The 16S rRNA gene was polymerase chain reaction amplified, sequenced on a MiSeq platform, and analyzed using a MOTHUR- UPARSE pipeline.
Results: Here we show that spared nerve injury-induced neuropathic pain alters gut microbial diversity in mice. We successfully constructed reliable microbial interaction networks using the Metagenomic Microbial Interaction Simulator (MetaMIS) and analyzed these networks based on 177,147 simulations. Interestingly, at a higher resolution, our results showed that spared nerve injury-induced neuropathic pain altered both the stability of the microbial community and the key microbes in a gut micro-ecosystem. Oscillospira, which was classified as a low-abundance and core microbe, was identified as the key microbe in the Sham group, whereas Staphylococcus, classified as a rare and non-core microbe, was identified as the key microbe in the spared nerve injury-induced neuropathic pain group.
Conclusions: In summary, our results provide novel experimental evidence that spared nerve injury-induced neuropathic pain reshapes gut microbial diversity, and alters the stability and key microbes in the gut.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementarymaterialsDaryiWangrevised.docx
Supplemental Figure 1. Assessment of sufficient sequencing depth by rarefaction analyses. Individual rarefaction curves for each time-series sample from the Sham (blue) or SNI (red) group. Supplemental Figure 2: Multiple linear regression analyses for the final ranks of microbes and centrality. A) Sham group (p value < 0.001; R2=0.9167), B) SNI group (p value < 0.001; R2=0.8877). Supplemental Figure 3: Simplified microbial interaction networks that highlight the positive and negative interactions among key microbes or probiotics within the networks. A) Microbial interaction network in the Sham group with Oscillospira (26) at the center; B) Staphylococcus (53) in the SNI group; C) Lactobacillus (17) in the Sham group; D) Lactobacillus (17) in the SNI group; E) Bifidobacterium (48) in the Sham group; F) Bifidobacterium (48) in the SNI group. Supplemental Table 1. Differential relative abundance between the SNI group and Sham group (n=6) for each day at the genus level using DESeq2. pvalue = the average of the normalized counts, log2FoldChange = log2 fold change between the groups, lfcSE = standard error of the log2FoldChange estimate, stat = Wald statistic, pvalue = Wald test p-value, padj = Benjamini-Hochberg adjusted p-value. Supplemental Table 2.1. The ranks and values of each genus in the Sham group based on betweenness centrality, closeness centrality, and degree centrality. Supplemental Table 2.2. The ranks and values of each genus in the SNI group based on betweenness centrality, closeness centrality, and degree centrality.
- NC3RsARRIVEGuidelinesChecklist2014DaryiWang.docx
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