Gut dysbiosis and brain microhemorrhages in young vs aged mice with chronic kidney disease

Intestinal dysbiosis and gut-derived toxins in chronic kidney diseases (CKD) are associated with vascular injury. This study examined the relationship between gut dysbiosis and cerebral microhemorrhages (CMH) in young and aged CKD mice (3 vs 16 months of age) in both sexes. CKD was induced in C57BL/6J mice using a nephrotoxic adenine diet. Serum creatinine, trimethylamine N-oxide (TMAO), indoxyl sulfate (IS), and p-cresyl sulfate (pCS) were measured. CMH was quantified via brain histology, and gut microbial sequencing was analyzed from fecal pellets. Creatinine and uremic toxins were elevated in both young and aged CKD mice compared to controls, and microbial populations were altered by age, sex, and CKD status. Age was the most significant factor in microbial variance, with higher levels of IS and pCS in aged CKD mice. Aged male mice had significantly higher creatinine, TMAO, and IS than aged females. Males had higher CMH counts than females, and aged CKD males had the highest CMH burd...,
Animal model
All animal studies were approved by the Animal Research Committee, University of California, Irvine (UCI) under protocol AUP-21-157. Animals were maintained at the UCI vivarium in accordance with the policies instituted by the American Association for Accreditation of Laboratory Animal Care. Tubulointerstitial nephritis was induced via nephrotoxic adenine diet in adult C57BL/6J mice (Figure 5). Young mice (10-12 weeks old, Jackson Laboratories, Bar Harbor, ME)) and aged mice (16 months old, National Institute on Aging aged rodent colony) were fed a diet containing 0.2% adenine for 18 days (Dyet# 611732, Dyets Inc., Bethlehem, PA), placed back on regular chow for 2 weeks, and then re-exposed to adenine diet for 1 week to maintain CKD 11,13. Control (CTL) age-matched animals were maintained on regular feed for the duration of the experiment. Studies were done in both male and female animals.

Tissue collection
At study termination, the chest cavity was opened, and blood was ..., # Gut dysbiosis and brain microhemorrhages in young vs aged mice with chronic kidney disease

Dataset DOI: [10.5061/dryad.95x69p8x2](10.5061/dryad.95x69p8x2)

## Description of the data and file structure

Data Files included:

1. gut_microbiome_sequencing_data_with_biosample_IDs_young_vs_aged_mice.xlsx

Contains information of gut microbiome sequecing data including accession number, samples name, SPUID, organism, Tax ID, BioProject number, and object IDs and corresponding URLs.
2. Young_vs_aged_mice_master_dataset_Dryad.xlsx

Contains the raw data including mouse ID, markers of kidney function, levels of uremic toxins, sizes and counts of cerebral microhemorrhages, and Shannon diversity. 
3. descriptive_stats_Dryad.xlsx

Contains descriptive data including mean values, standard deviation, and standard error of mean values of Creatinine, uremic toxins, as well as counts, average size and standarized surface area of CMH in all groups. 
4. Supplementary Data:
1. 2023-05_Gut_m...,