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BACKGROUND:Resistant starch is a prebiotic metabolized by the gut bacteria. It has been shown to attenuate chronic kidney disease (CKD) progression in rats. Previous studies employed taxonomic analysis using 16S rRNA sequencing and untargeted metabolomics profiling. Here we expand these studies by metaproteomics, gaining new insight into the host-microbiome interaction. METHODS:Differences between cecum contents in CKD rats fed a diet containing resistant starch with those fed a diet containing digestible starch were examined by comparative metaproteomics analysis. Taxonomic information was obtained using unique protein sequences. Our methodology results in quantitative data covering both host and bacterial proteins. RESULTS:5,834 proteins were quantified, with 947 proteins originating from the host organism. Taxonomic information derived from metaproteomics data surpassed previous 16S RNA analysis, and reached species resolutions for moderately abundant taxonomic groups. In particular, the Ruminococcaceae family becomes well resolved-with butyrate producers and amylolytic species such as R. bromii clearly visible and significantly higher while fibrolytic species such as R. flavefaciens are significantly lower with resistant starch feeding. The observed changes in protein patterns are consistent with fiber-associated improvement in CKD phenotype. Several known host CKD-associated proteins and biomarkers of impaired kidney function were significantly reduced with resistant starch supplementation. Data are available via ProteomeXchange with identifier PXD008845. CONCLUSIONS:Metaproteomics analysis of cecum contents of CKD rats with and without resistant starch supplementation reveals changes within gut microbiota at unprecedented resolution, providing both functional and taxonomic information. Proteins and organisms differentially abundant with RS supplementation point toward a shift from mucin degraders to butyrate producers.

The space extending beyond Earth's magnetosphere is subject to a complex field of high-energy charged nuclei, which are capable of traversing spacecraft shielding and human tissues, inducing dense ionization events. The central nervous system is a major area of concern for astronauts who will be exposed to the deep-space radiation environment on a mission to Mars, as charged-particle radiation has been shown to elicit changes to the dendritic arbor within the hippocampus of rodents, and related cognitive-behavioral deficits. We exposed 6-month-old male mice to whole-body 1H (0.5 Gy; 150 MeV/n; 18–19 cGy/minute) and an hour later to 16O (0.1Gy; 600 MeV/n; 18–33 Gy/min) at NASA's Space Radiation Laboratory as a galactic cosmic ray-relevant model. Animals were housed with bedding which provides cognitive enrichment. Mice were tested for cognitive behavior 9 months after exposure to elucidate late radiation effects. Radiation induced significant deficits in novel object recognition and short-term spatial memory (Y-maze). Additionally, we observed opposing morphological differences between the mature granular and pyramidal neurons throughout the hippocampus, with increased dendritic length in the dorsal dentate gyrus and reduced length and complexity in the CA1 subregion of the hippocampus. Dendritic spine analyses revealed a severe reduction in mushroom spine density throughout the hippocampus of irradiated animals. Finally, we detected no general effect of radiation on single-nucleotide polymorphisms in immediate early genes, and genes involved in inflammation but found a higher variant allele frequency in the antioxidants thioredoxin reductase 2 and 3 loci. [ABSTRACT FROM AUTHOR]

Competing Interests: None

The space extending beyond Earth's magnetosphere is subject to a complex field of high-energy charged nuclei, which are capable of traversing spacecraft shielding and human tissues, inducing dense ionization events. The central nervous system is a major area of concern for astronauts who will be exposed to the deep-space radiation environment on a mission to Mars, as charged-particle radiation has been shown to elicit changes to the dendritic arbor within the hippocampus of rodents, and related cognitive-behavioral deficits. We exposed 6-month-old male mice to whole-body 1 H (0.5 Gy; 150 MeV/n; 18-19 cGy/minute) and an hour later to 16 O (0.1Gy; 600 MeV/n; 18-33 Gy/min) at NASA's Space Radiation Laboratory as a galactic cosmic ray-relevant model. Animals were housed with bedding which provides cognitive enrichment. Mice were tested for cognitive behavior 9 months after exposure to elucidate late radiation effects. Radiation induced significant deficits in novel object recognition and short-term spatial memory (Y-maze). Additionally, we observed opposing morphological differences between the mature granular and pyramidal neurons throughout the hippocampus, with increased dendritic length in the dorsal dentate gyrus and reduced length and complexity in the CA1 subregion of the hippocampus. Dendritic spine analyses revealed a severe reduction in mushroom spine density throughout the hippocampus of irradiated animals. Finally, we detected no general effect of radiation on single-nucleotide polymorphisms in immediate early genes, and genes involved in inflammation but found a higher variant allele frequency in the antioxidants thioredoxin reductase 2 and 3 loci., (Copyright © 2020 Kiffer, Alexander, Anderson, Groves, McElroy, Wang, Sridharan, Bauer, Boerma and Allen.)