Muscle atrophy phenotype gene expression during spaceflight is linked to a metabolic crosstalk in both the liver and the muscle in mice

Vitry, Géraldine; Finch, Rebecca; McStay, Gavin P.; Behesti, Afshin; Déjean, Sébastien; Larose, Tricia L; Wotring, Virginia E.; Silveira, Willian A. da

doi:10.1016/j.isci.2022.105213

Cited by 14 publications

(11 citation statements)

References 57 publications

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“…In mice, changes in microbially produced butyrate are also know to directly influence expression of hepatic circadian clock regulating genes, such as Per2 and Bmal1, in a bidirectional interaction which can disrupt host metabolism 53 . Enrichment of D. welbionis in both groups of spaceflight mice (fig 3ABIJ) compared to their respective ground controls here is therefore noteworthy given the high lipid accumulation, liver and mitochondrial dysfunction phenotype repeatedly observed in rodent research missions and astronauts 17,18,45 . Whether the relative increase of this species might be counteracting or contributing towards spaceflight pathology is unclear and merits further study.…”

Section: Spaceflight Alters Murine Gut Microbiotamentioning

confidence: 66%

“…Insulin resistance and lipid accumulation are common spaceflight phenotypes 45 which are influenced by short chain fatty acids (SCFAs) and can be improved through butyrate dietary interventions in ground-based murine studies 46,47 . As butyrate and other SCFAs are predominantly produced by bacteria within the gut 48 , alterations in RR6 gut microbiome composition were explored.…”

Section: Resultsmentioning

confidence: 99%

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Spaceflight alters host-gut microbiota interactions

Gonzalez,

Lee,

Tierney

et al. 2024

Preprint

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The rodent habitat on the International Space Station has provided crucial insights into the impact of spaceflight on mammals, including observation of symptoms characteristic of liver disease, insulin resistance, osteopenia and myopathy. Although these physiological responses can involve the microbiome when observed on Earth, changes in host-microbiota interactions during spaceflight are still being elucidated. Here, NASA GeneLab multiomic data from the Rodent Research 6 mission are used to determine changes to gut microbiota and murine host colon and liver gene expression after 29 and 56-days of spaceflight. Using hybrid amplicon and whole metagenome sequencing analysis, significant spaceflight-associated alterations to 42 microbiome species were identified. These included relative reductions of bacteria associated with bile acid and butyrate metabolism, such as Extibacter muris and Dysosmobacter welbionis. Functional prediction suggested over-representation of fatty acid and bile acid metabolism, extracellular matrix interactions, and antibiotic resistance genes within the gut microbiome, while host intestinal and hepatic gene expression described corresponding changes to host bile acid and energy metabolism, and immune suppression from spaceflight. Taken together, these changes imply that interactions at the host-gut microbiome interface contribute to spaceflight pathology and highlight how these interactions might critically influence human health and the feasibility of long-duration spaceflight.

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Section: Spaceflight Alters Murine Gut Microbiotamentioning

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Spaceflight alters host-gut microbiota interactions

Gonzalez,

Lee,

Tierney

et al. 2024

Preprint

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“…Importantly, as ESA does not have on-orbit rodent research facilites, we encourage ESA community researchers to use rodent data collected by NASA and JAXA. For example, using such data, a recent ESA Space Omics Topical Team study has confirmed cross-tissue coordination underlying omic changes in mice in flight 23 . In terms of human subjects, the ESA Space Omics Topical Team has recently suggested that this should be a priority 19 , 24 , a view we support.…”

Section: Proposed Research Activities To Fulfill Open Scientific Ques...mentioning

confidence: 93%

How to obtain an integrated picture of the molecular networks involved in adaptation to microgravity in different biological systems?

Willis,

Calvaruso,

Angeloni

et al. 2024

npj Microgravity

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Periodically, the European Space Agency (ESA) updates scientific roadmaps in consultation with the scientific community. The ESA SciSpacE Science Community White Paper (SSCWP) 9, “Biology in Space and Analogue Environments”, focusses in 5 main topic areas, aiming to address key community-identified knowledge gaps in Space Biology. Here we present one of the identified topic areas, which is also an unanswered question of life science research in Space: “How to Obtain an Integrated Picture of the Molecular Networks Involved in Adaptation to Microgravity in Different Biological Systems?” The manuscript reports the main gaps of knowledge which have been identified by the community in the above topic area as well as the approach the community indicates to address the gaps not yet bridged. Moreover, the relevance that these research activities might have for the space exploration programs and also for application in industrial and technological fields on Earth is briefly discussed.

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“…To fill this gap, diverse omics approaches have been conducted with a cohort of flight samples, including ones from astronauts ( 7, 8 ). These studies explored the epigenome, transcriptome, proteome, and metabolome ( 3, 9–18 ) and indicated microgravity-mediated gene expression profile changes associated with the hazardous phenotypes mentioned above. However, these conventional spaceflight studies have lacked investigation of translational regulation, an acute and inducible means to reprogram protein expression ( 19–22 ).…”

Section: Introductionmentioning

confidence: 99%

Gravitational and mechanical forces drive mitochondrial translation

Wakigawa

Kimura

Mito

et al. 2023

Preprint

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Life on Earth has evolved in a form suitable for the gravitational force of 1 × g. Although the pivotal role of gravity in gene expression has been revealed by multiomics approaches in space-flown samples and astronauts, the molecular details of how mammalian cells harness gravity have remained unclear. Here, we show that mitochondria utilize gravity to activate protein synthesis within the organelle. Genome-wide ribosome profiling unveiled reduced mitochondrial translation in mammalian cells and Caenorhabditis elegans under microgravity in the International Space Station and under simulated microgravity in the 3D-clinostat on the ground. In addition, we found that cell adhesion through laminin–integrin interaction, which is attenuated by microgravity, and the downstream FAK, RAC1, PAK1, BAD, and Bcl-2 family proteins relay the signals for mitochondrial protein synthesis. Consistent with the role of integrin as a mechanosensor, we observed the decrease in mitochondrial translation by minimization of mechanical stress in mouse skeletal muscle. Our work provides mechanistic insights into how cells convert gravitational and mechanical forces into translation in an energy-producing organelle.

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Muscle atrophy phenotype gene expression during spaceflight is linked to a metabolic crosstalk in both the liver and the muscle in mice

Cited by 14 publications

References 57 publications

Spaceflight alters host-gut microbiota interactions

Spaceflight alters host-gut microbiota interactions

How to obtain an integrated picture of the molecular networks involved in adaptation to microgravity in different biological systems?

Gravitational and mechanical forces drive mitochondrial translation

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