Commensal microbiota regulate renal gene expression in a sex-specific manner.
Authors Moore BN, Pluznick JL
Submitted By Submitted Externally on 4/25/2024
Status Published
Journal American journal of physiology. Renal physiology
Year 2023
Date Published 6/1/2023
Volume : Pages 324 : F511 - F520
PubMed Reference 37053490
Abstract The gut microbiome impacts host gene expression not only in the colon but also
at distal sites including the liver, white adipose tissue, and spleen. The gut
microbiome also influences the kidney and is associated with renal diseases and
pathologies; however, a role for the gut microbiome to modulate renal gene
expression has not been examined. To determine if microbes modulate renal gene
expression, we used whole organ RNA sequencing to compare gene expression in
C57Bl/6 mice that were germ free (lacking gut microbiota) versus
conventionalized (gut microbiota reintroduced using an oral gavage of a fecal
slurry composed of mixed stool). 16S sequencing showed that male and female mice
were similarly conventionalized, although Verrucomicrobia was higher in male
mice. We found that renal gene expression was differentially regulated in the
presence vs. absence of microbiota and that these changes were largely sex
specific. Although microbes also influenced gene expression in the liver and
large intestine, most differentially expressed genes (DEGs) in the kidney were
not similarly regulated in the liver or large intestine. This demonstrates that
the influence of the gut microbiota on gene expression is tissue specific.
However, a minority of genes (n = 4 in males and n = 6 in females) were
similarly regulated in all three tissues examined, including genes associated
with circadian rhythm (period 1 in males and period 2 in females) and metal
binding (metallothionein 1 and metallothionein 2 in both males and females).
Finally, using a previously published single-cell RNA-sequencing dataset, we
assigned a subset of DEGs to specific kidney cell types, revealing clustering of
DEGs by cell type and/or sex.NEW & NOTEWORTHY It is unknown whether the
microbiome influences host gene expression in the kidney. Here, we utilized an
unbiased, bulk RNA-sequencing approach to compare gene expression in the kidneys
of male and female mice with or without gut microbiota. This report demonstrates
that renal gene expression is modulated by the microbiome in a sex- and
tissue-specific manner.

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