Evidence map›Paper›PMID 37932822›Full record

ArticleBiology of sex differences2023

Genetic hypogonadal mouse model reveals niche-specific influence of reproductive axis and sex on intestinal microbial communities.

Laura Sisk-Hackworth, Jada Brown, Lillian Sau, Andrew A Levine, Lai Ying Ivy Tam, Aishwarya Ramesh, Reeya S Shah, Evelyn T Kelley-Thackray, Sophia Wang, Anita Nguyen and 2 more

Open access · goldAbstract read
In one paragraph

Article in Biology of sex differences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Characterization of the gut microbiome of wildFrontiers in microbiomes · 2026
    Article
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  8. Genetic hypogonadal (Gnrh1bioRxiv : the preprint server for biology · 2024
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Laura Sisk-HackworthUniversity of California San Diego, La Jolla, CA, USA.
Jada BrownUniversity of California San Diego, La Jolla, CA, USA.
Lillian SauUniversity of California San Diego, La Jolla, CA, USA.
Andrew A LevineSan Diego State University, San Diego, CA, USA.
Lai Ying Ivy TamUniversity of California San Diego, La Jolla, CA, USA.
Aishwarya RameshUniversity of California San Diego, La Jolla, CA, USA.
Reeya S ShahUniversity of California San Diego, La Jolla, CA, USA.
Evelyn T Kelley-ThackrayUniversity of California San Diego, La Jolla, CA, USA.
Sophia WangUniversity of California San Diego, La Jolla, CA, USA.
Anita NguyenUniversity of California San Diego, La Jolla, CA, USA.
Scott T KelleySan Diego State University, San Diego, CA, USA.
Varykina G ThackrayUniversity of California San Diego, La Jolla, CA, USA. vthackray@health.ucsd.edu.ORCID 0000-0002-6672-6117
University of California San Diego · USSan Diego State University · USUC San Diego Health System · US

Funding

Role of the Gut Microbiome in Polycystic Ovary SyndromeR01HD095412 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI THACKRAY, VARYKINA G · 2019 to 2023
$2.3M
Investigating the Role of Puberty in the Sex-Specific Maturation of the Gut MicrobiomeF31HD105403 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SISK-HACKWORTH, LAURA GILMAN · 2021 to 2023
$111k
NICHD NIH HHS F31 HD105403NICHD NIH HHS R01 HD095412
6 · The paper itself

Abstract

backgroundThe gut microbiome has been linked to many diseases with sex bias including autoimmune, metabolic, neurological, and reproductive disorders. While numerous studies report sex differences in fecal microbial communities, the role of the reproductive axis in this differentiation is unclear and it is unknown how sex differentiation affects microbial diversity in specific regions of the small and large intestine.

methodsWe used a genetic hypogonadal mouse model that does not produce sex steroids or go through puberty to investigate how sex and the reproductive axis impact bacterial diversity within the intestine. Using 16S rRNA gene sequencing, we analyzed alpha and beta diversity and taxonomic composition of fecal and intestinal communities from the lumen and mucosa of the duodenum, ileum, and cecum from adult female (n = 20) and male (n = 20) wild-type mice and female (n = 17) and male (n = 20) hypogonadal mice.

resultsBoth sex and reproductive axis inactivation altered bacterial composition in an intestinal section and niche-specific manner. Hypogonadism was significantly associated with bacteria from the Bacteroidaceae, Eggerthellaceae, Muribaculaceae, and Rikenellaceae families, which have genes for bile acid metabolism and mucin degradation. Microbial balances between males and females and between hypogonadal and wild-type mice were also intestinal section-specific. In addition, we identified 3 bacterial genera (Escherichia Shigella, Lachnoclostridium, and Eggerthellaceae genus) with higher abundance in wild-type female mice throughout the intestinal tract compared to both wild-type male and hypogonadal female mice, indicating that activation of the reproductive axis leads to female-specific differentiation of the gut microbiome. Our results also implicated factors independent of the reproductive axis (i.e., sex chromosomes) in shaping sex differences in intestinal communities. Additionally, our detailed profile of intestinal communities showed that fecal samples do not reflect bacterial diversity in the small intestine.

conclusionsOur results indicate that sex differences in the gut microbiome are intestinal niche-specific and that sampling feces or the large intestine may miss significant sex effects in the small intestine. These results strongly support the need to consider both sex and reproductive status when studying the gut microbiome and while developing microbial-based therapies.

Indexed as

Gastrointestinal MicrobiomeMicrobiotaAnimalsBacteriaFecesFemaleHumansIleumMaleMiceRNA, Ribosomal, 16SRNA, Ribosomal, 16S

Identifiers

PMID37932822
PMCPMC10626657
OpenAlexW4388405791

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.