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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.

SUBMITTER: Elderman M

PROVIDER: S-EPMC6006852 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Elderman Marlies M Hugenholtz Floor F Belzer Clara C Boekschoten Mark M van Beek Adriaan A de Haan Bart B Savelkoul Huub H de Vos Paul P Faas Marijke M

Biology of sex differences 20180618 1

<h4>Background</h4>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.<h4>Methods</h4>Fecal microbiota composition (MITchip), mRNA expression in intestinal tissue (microarray), and immune cell populations ...[more]

PMID: 29914546

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Project description:Sex hormone secretion difference is one of the main reasons for sexually dimorphic traits in animals, which affects the dimorphism of the intestinal microbiota; however, their interaction is still unknown. Intestinal mucosa-associated microbiota (MAM) and intestinal luminal content microbiota (LM) belong to two different habitats according to the difference in interactions between bacteria and host intestinal epithelium/nutrients. To clarify the sexually dimorphic characteristics of MAM and LM and their correlation with sex hormones, 12 specific pathogen-free (SPF) Kunming mice from the same nest were fed separately according to sex. After 8 weeks, samples from the male intestinal mucosa group (MM group), the female intestinal mucosa group (FM group), the male intestinal content group (MC group), and the female intestinal content group (FC group) were collected and then, the next-generation sequencing of 16S ribosomal ribonucleic acid (rRNA) gene was performed. Our results showed that the sexual dimorphism of MAM was more obvious than that of LM and the relative abundance of Muribaculaceae, Turicibacter, and Parasutterella was significantly higher in the FM group than in the MM group (p < 0.001, p < 0.05, p < 0.05). Next, we measured the level of serum sex hormones in mice and calculated the correlation coefficient between major bacteria and sex hormones. The results showed that the correlation between MAM and sex hormones was more prominent, and finally, three bacterial genera (Muribaculaceae, Turicibacter, and Parasutterella) were obtained, which could better represent the relationship between sexual dimorphism and sex hormones. The abundance of Parasutterella is positively and negatively correlated with estradiol and testosterone (T), respectively, which may be related to the differences in the metabolism of bile acid and glucose. A decrease in the abundance of Turicibacter is closely related to autism. Our results show that the abundance of Turicibacter is negatively and positively correlated with T and estradiol, respectively, which can provide a hint for the prevalence of male autism. In conclusion, it is proposed in our study that intestinal microbiota is probably the biological basis of physiological and pathological differences due to sex, and intestinal MAM can better represent the sexual dimorphism of mice.

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

Publications

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

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