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Research Article
Starvation causes changes in the intestinal transcriptome and microbiome that are reversed upon refeeding
John Rawls
Duke University
Corresponding Author
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Background: The ability of animals and their microbiomes to adapt to starvation and then restore homeostasis after refeeding is fundamental to their continued survival and symbiosis. The intestine is the primary site of nutrient absorption and microbiome interaction, however our understanding of intestinal adaptations in host transcriptional programs and microbiome composition remains limited. Additionally, few studies on starvation have investigated intestinal responses to refeeding. The zebrafish presents unique opportunities to study the effects of long-term starvation and refeeding. We used RNA sequencing and 16S rRNA gene sequencing to uncover changes in the intestinal transcriptome and microbiome of zebrafish subjected to long-term starvation and refeeding compared to continuously fed controls.
Results: Starvation over 21 days led to increased diversity and altered composition in the intestinal microbiome compared to fed controls, including relative increases in Vibrio and reductions in Plesiomonas bacteria. Starvation also led to significant alterations in host gene expression in the intestine, with distinct pathways affected at early and late stages of starvation. This included increases in the expression of ribosome biogenesis genes early in starvation, followed by decreased expression of genes involved in antiviral immunity and at later stages. These effects of starvation on the host transcriptome and microbiome were within 3 days after refeeding. Comparison with published datasets identified host genes responsive to starvation as well as high-fat feeding or microbiome colonization, and predicted host transcription factors that may be involved in starvation response.
Conclusions: Long-term starvation induces progressive changes in microbiome composition and host gene expression in the zebrafish intestine, and these changes are rapidly reversed after refeeding. Our identification of bacterial taxa, host genes and host pathways involved in this response provides a framework for future investigation of the physiological and ecological mechanisms underlying intestinal adaptations to food restriction.
Keywords
starvation, microbiome, refeeding, homeostasis
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CURRENT STATUS: Under Revision
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Posted 16 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 28 Jan, 2021
Review #2 received
Received 18 Jan, 2021
Review #1 received
Received 18 Jan, 2021
Review #3 received
Received 18 Jan, 2021
Review #4 received
Received 18 Jan, 2021
Reviewer #4 agreed
On 13 Jan, 2021
Reviewer #3 agreed
On 13 Jan, 2021
Reviewer #5 agreed
On 13 Jan, 2021
Reviewer #2 agreed
On 13 Jan, 2021
Reviewer #7 agreed
On 07 Jan, 2021
Reviewer #1 agreed
On 07 Jan, 2021
Reviewer #12 agreed
On 07 Jan, 2021
Reviewer #11 agreed
On 07 Jan, 2021
Reviewer #8 agreed
On 07 Jan, 2021
Reviewer #6 agreed
On 07 Jan, 2021
Reviewer #13 agreed
On 07 Jan, 2021
Reviewer #14 agreed
On 07 Jan, 2021
Reviewer #10 agreed
On 07 Jan, 2021
Reviewer #9 agreed
On 07 Jan, 2021
Reviewers invited
Invitations sent on 29 Dec, 2020
Editor assigned
On 15 Dec, 2020
Editor invited
On 15 Dec, 2020
Submission checks complete
On 15 Dec, 2020
First submitted
On 02 Dec, 2020
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Subject Areas
Epigenetics & Genomics
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This preprint is under consideration at BMC Genomics. A preprint is 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
Starvation causes changes in the intestinal transcriptome and microbiome that are reversed upon refeeding
John Rawls
Duke University
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: Under Revision
Version 1
Posted 16 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 28 Jan, 2021
Review #2 received
Received 18 Jan, 2021
Review #1 received
Received 18 Jan, 2021
Review #3 received
Received 18 Jan, 2021
Review #4 received
Received 18 Jan, 2021
Reviewer #4 agreed
On 13 Jan, 2021
Reviewer #3 agreed
On 13 Jan, 2021
Reviewer #5 agreed
On 13 Jan, 2021
Reviewer #2 agreed
On 13 Jan, 2021
Reviewer #7 agreed
On 07 Jan, 2021
Reviewer #1 agreed
On 07 Jan, 2021
Reviewer #12 agreed
On 07 Jan, 2021
Reviewer #11 agreed
On 07 Jan, 2021
Reviewer #8 agreed
On 07 Jan, 2021
Reviewer #6 agreed
On 07 Jan, 2021
Reviewer #13 agreed
On 07 Jan, 2021
Reviewer #14 agreed
On 07 Jan, 2021
Reviewer #10 agreed
On 07 Jan, 2021
Reviewer #9 agreed
On 07 Jan, 2021
Reviewers invited
Invitations sent on 29 Dec, 2020
Editor assigned
On 15 Dec, 2020
Editor invited
On 15 Dec, 2020
Submission checks complete
On 15 Dec, 2020
First submitted
On 02 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Epigenetics & Genomics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The ability of animals and their microbiomes to adapt to starvation and then restore homeostasis after refeeding is fundamental to their continued survival and symbiosis. The intestine is the primary site of nutrient absorption and microbiome interaction, however our understanding of intestinal adaptations in host transcriptional programs and microbiome composition remains limited. Additionally, few studies on starvation have investigated intestinal responses to refeeding. The zebrafish presents unique opportunities to study the effects of long-term starvation and refeeding. We used RNA sequencing and 16S rRNA gene sequencing to uncover changes in the intestinal transcriptome and microbiome of zebrafish subjected to long-term starvation and refeeding compared to continuously fed controls.
Results: Starvation over 21 days led to increased diversity and altered composition in the intestinal microbiome compared to fed controls, including relative increases in Vibrio and reductions in Plesiomonas bacteria. Starvation also led to significant alterations in host gene expression in the intestine, with distinct pathways affected at early and late stages of starvation. This included increases in the expression of ribosome biogenesis genes early in starvation, followed by decreased expression of genes involved in antiviral immunity and at later stages. These effects of starvation on the host transcriptome and microbiome were within 3 days after refeeding. Comparison with published datasets identified host genes responsive to starvation as well as high-fat feeding or microbiome colonization, and predicted host transcription factors that may be involved in starvation response.
Conclusions: Long-term starvation induces progressive changes in microbiome composition and host gene expression in the zebrafish intestine, and these changes are rapidly reversed after refeeding. Our identification of bacterial taxa, host genes and host pathways involved in this response provides a framework for future investigation of the physiological and ecological mechanisms underlying intestinal adaptations to food restriction.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.