Sex and strain dependent differences in mucosal immunology and microbiota composition in mice

Marlies Elderman, Floor Hugenholtz, Clara Belzer, Mark Boekschoten, Adriaan van Beek, Bart de Haan, Huub Savelkoul, Paul de Vos, Marijke Faas

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)

Abstract

Background: A dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. These diseases often show a sex bias, suggesting sex differences in immune responses and in the intestinal microbiome. We hypothesized that sex differences in immune responses are associated with sex differences in microbiota composition. Methods: Fecal microbiota composition (MITchip), mRNA expression in intestinal tissue (microarray), and immune cell populations in mesenteric lymph nodes (MLNs) were studied in male and female mice of two mouse strains (C57B1/6OlaHsd and Balb/cOlaHsd). Transcriptomics and microbiota data were combined to identify bacterial species which may potentially be related to sex-specific differences in intestinal immune related genes. Results: We found clear sex differences in intestinal microbiota species, diversity, and richness in healthy mice. However, the nature of the sex effects appeared to be determined by the mouse strain as different bacterial species were enriched in males and females of the two strains. For example, Lactobacillus plantarum and Bacteroides distasonis were enriched in B6 females as compared to B6 males, while Bifidobacterium was enriched BALB/c females as compared to BALB/c males. The strain-dependent sex effects were also observed in the expression of immunological genes in the colon. We found that the abundance of various bacteria (e.g., Clostridium leptum et rel.) which were enriched in B6 females positively correlated with the expression of several genes (e.g., Il-2rb, Ccr3, and Cd80) which could be related to immunological functions, such as inflammatory responses and migration of leukocytes. The abundance of several bacteria (e.g., Faecalibacterium prausnitzii et rel. and Coprobacillus et rel.- Clostridium ramosum et rel.) which were enriched in BALB/c males positively correlated to the expression of several genes (e.g., Apoe, Il-1b, and Stat4) related to several immunological functions, such as proliferation and quantity of lymphocytes. The net result was the same, since both mouse strains showed similar sex induced differences in immune cell populations in the MLNs. Conclusions: Our data suggests a correlation between microbiota and intestinal immune populations in a sex and strain-specific way. These findings may contribute to the development of more sex and genetic specific treatments for intestinal-related disorders.
Original languageEnglish
Article number26
JournalBiology of Sex Differences
Volume9
DOIs
Publication statusPublished - 18 Jun 2018

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Microbiota
Allergy and Immunology
Sex Characteristics
Disease
Clostridium
Gene Expression
proliferation
Lymph Nodes
Dysbiosis
migration
Population
Bacteria
Sexism
Lactobacillus plantarum
Sexual Development
Bacteroides
Bifidobacterium
Immune System Diseases
Apolipoproteins E
trend

Cite this

Elderman, Marlies ; Hugenholtz, Floor ; Belzer, Clara ; Boekschoten, Mark ; van Beek, Adriaan ; de Haan, Bart ; Savelkoul, Huub ; de Vos, Paul ; Faas, Marijke. / Sex and strain dependent differences in mucosal immunology and microbiota composition in mice. In: Biology of Sex Differences. 2018 ; Vol. 9.
@article{863256c46de44017821e358fc1b90e06,
title = "Sex and strain dependent differences in mucosal immunology and microbiota composition in mice",
abstract = "Background: A dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. These diseases often show a sex bias, suggesting sex differences in immune responses and in the intestinal microbiome. We hypothesized that sex differences in immune responses are associated with sex differences in microbiota composition. Methods: Fecal microbiota composition (MITchip), mRNA expression in intestinal tissue (microarray), and immune cell populations in mesenteric lymph nodes (MLNs) were studied in male and female mice of two mouse strains (C57B1/6OlaHsd and Balb/cOlaHsd). Transcriptomics and microbiota data were combined to identify bacterial species which may potentially be related to sex-specific differences in intestinal immune related genes. Results: We found clear sex differences in intestinal microbiota species, diversity, and richness in healthy mice. However, the nature of the sex effects appeared to be determined by the mouse strain as different bacterial species were enriched in males and females of the two strains. For example, Lactobacillus plantarum and Bacteroides distasonis were enriched in B6 females as compared to B6 males, while Bifidobacterium was enriched BALB/c females as compared to BALB/c males. The strain-dependent sex effects were also observed in the expression of immunological genes in the colon. We found that the abundance of various bacteria (e.g., Clostridium leptum et rel.) which were enriched in B6 females positively correlated with the expression of several genes (e.g., Il-2rb, Ccr3, and Cd80) which could be related to immunological functions, such as inflammatory responses and migration of leukocytes. The abundance of several bacteria (e.g., Faecalibacterium prausnitzii et rel. and Coprobacillus et rel.- Clostridium ramosum et rel.) which were enriched in BALB/c males positively correlated to the expression of several genes (e.g., Apoe, Il-1b, and Stat4) related to several immunological functions, such as proliferation and quantity of lymphocytes. The net result was the same, since both mouse strains showed similar sex induced differences in immune cell populations in the MLNs. Conclusions: Our data suggests a correlation between microbiota and intestinal immune populations in a sex and strain-specific way. These findings may contribute to the development of more sex and genetic specific treatments for intestinal-related disorders.",
author = "Marlies Elderman and Floor Hugenholtz and Clara Belzer and Mark Boekschoten and {van Beek}, Adriaan and {de Haan}, Bart and Huub Savelkoul and {de Vos}, Paul and Marijke Faas",
year = "2018",
month = "6",
day = "18",
doi = "10.1186/s13293-018-0186-6",
language = "English",
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Sex and strain dependent differences in mucosal immunology and microbiota composition in mice. / Elderman, Marlies; Hugenholtz, Floor; Belzer, Clara; Boekschoten, Mark; van Beek, Adriaan; de Haan, Bart; Savelkoul, Huub; de Vos, Paul; Faas, Marijke.

In: Biology of Sex Differences, Vol. 9, 26, 18.06.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Sex and strain dependent differences in mucosal immunology and microbiota composition in mice

AU - Elderman, Marlies

AU - Hugenholtz, Floor

AU - Belzer, Clara

AU - Boekschoten, Mark

AU - van Beek, Adriaan

AU - de Haan, Bart

AU - Savelkoul, Huub

AU - de Vos, Paul

AU - Faas, Marijke

PY - 2018/6/18

Y1 - 2018/6/18

N2 - Background: A dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. These diseases often show a sex bias, suggesting sex differences in immune responses and in the intestinal microbiome. We hypothesized that sex differences in immune responses are associated with sex differences in microbiota composition. Methods: Fecal microbiota composition (MITchip), mRNA expression in intestinal tissue (microarray), and immune cell populations in mesenteric lymph nodes (MLNs) were studied in male and female mice of two mouse strains (C57B1/6OlaHsd and Balb/cOlaHsd). Transcriptomics and microbiota data were combined to identify bacterial species which may potentially be related to sex-specific differences in intestinal immune related genes. Results: We found clear sex differences in intestinal microbiota species, diversity, and richness in healthy mice. However, the nature of the sex effects appeared to be determined by the mouse strain as different bacterial species were enriched in males and females of the two strains. For example, Lactobacillus plantarum and Bacteroides distasonis were enriched in B6 females as compared to B6 males, while Bifidobacterium was enriched BALB/c females as compared to BALB/c males. The strain-dependent sex effects were also observed in the expression of immunological genes in the colon. We found that the abundance of various bacteria (e.g., Clostridium leptum et rel.) which were enriched in B6 females positively correlated with the expression of several genes (e.g., Il-2rb, Ccr3, and Cd80) which could be related to immunological functions, such as inflammatory responses and migration of leukocytes. The abundance of several bacteria (e.g., Faecalibacterium prausnitzii et rel. and Coprobacillus et rel.- Clostridium ramosum et rel.) which were enriched in BALB/c males positively correlated to the expression of several genes (e.g., Apoe, Il-1b, and Stat4) related to several immunological functions, such as proliferation and quantity of lymphocytes. The net result was the same, since both mouse strains showed similar sex induced differences in immune cell populations in the MLNs. Conclusions: Our data suggests a correlation between microbiota and intestinal immune populations in a sex and strain-specific way. These findings may contribute to the development of more sex and genetic specific treatments for intestinal-related disorders.

AB - Background: A dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. These diseases often show a sex bias, suggesting sex differences in immune responses and in the intestinal microbiome. We hypothesized that sex differences in immune responses are associated with sex differences in microbiota composition. Methods: Fecal microbiota composition (MITchip), mRNA expression in intestinal tissue (microarray), and immune cell populations in mesenteric lymph nodes (MLNs) were studied in male and female mice of two mouse strains (C57B1/6OlaHsd and Balb/cOlaHsd). Transcriptomics and microbiota data were combined to identify bacterial species which may potentially be related to sex-specific differences in intestinal immune related genes. Results: We found clear sex differences in intestinal microbiota species, diversity, and richness in healthy mice. However, the nature of the sex effects appeared to be determined by the mouse strain as different bacterial species were enriched in males and females of the two strains. For example, Lactobacillus plantarum and Bacteroides distasonis were enriched in B6 females as compared to B6 males, while Bifidobacterium was enriched BALB/c females as compared to BALB/c males. The strain-dependent sex effects were also observed in the expression of immunological genes in the colon. We found that the abundance of various bacteria (e.g., Clostridium leptum et rel.) which were enriched in B6 females positively correlated with the expression of several genes (e.g., Il-2rb, Ccr3, and Cd80) which could be related to immunological functions, such as inflammatory responses and migration of leukocytes. The abundance of several bacteria (e.g., Faecalibacterium prausnitzii et rel. and Coprobacillus et rel.- Clostridium ramosum et rel.) which were enriched in BALB/c males positively correlated to the expression of several genes (e.g., Apoe, Il-1b, and Stat4) related to several immunological functions, such as proliferation and quantity of lymphocytes. The net result was the same, since both mouse strains showed similar sex induced differences in immune cell populations in the MLNs. Conclusions: Our data suggests a correlation between microbiota and intestinal immune populations in a sex and strain-specific way. These findings may contribute to the development of more sex and genetic specific treatments for intestinal-related disorders.

U2 - 10.1186/s13293-018-0186-6

DO - 10.1186/s13293-018-0186-6

M3 - Article

VL - 9

JO - Biology of Sex Differences

JF - Biology of Sex Differences

SN - 2042-6410

M1 - 26

ER -