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

Sex and strain dependent differences in mucosal immunology and microbiota composition in mice.
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DOI:
10.1186/s13293-018-0186-6
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发表时间:
2018-06-18
影响因子:
7.9
通讯作者:
Faas M
Faas M
中科院分区:
医学2区
文献类型:
--
作者:
Elderman M;Hugenholtz F;Belzer C;Boekschoten M;van Beek A;de Haan B;Savelkoul H;de Vos P;Faas M

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肠道微生物群失调在几种免疫性疾病的发病机制中起着重要作用。这些疾病通常表现出性别偏见,表明免疫反应和肠道微生物群的性别差异。我们假设,免疫反应中的性别差异与微生物区系组成的性别差异有关。对两个品系(C57B1/6OlaHsd和Balb/cOlaHsd)雄性和雌性小鼠的粪便微生物区系组成(MITChip)、肠道组织中的mRNA表达(微阵列)和肠系膜淋巴结(MLN)中的免疫细胞数进行了研究。转录组和微生物组数据相结合来鉴定细菌种类,这些细菌可能与肠道免疫相关基因的性别差异有关。我们在健康小鼠的肠道微生物区系的种类、多样性和丰富度方面发现了明显的性别差异。然而,性别影响的性质似乎是由老鼠品系决定的,因为两个品系的雄性和雌性体内都有不同的细菌种类。例如,植物乳杆菌和类杆菌在B6雌性中比B6雄性中丰富,而双歧杆菌在BALB/c雌性中比BALB/c雄性中丰富。在结肠免疫基因的表达上也观察到了品系依赖性的性别效应。我们发现各种细菌(如:淡色梭状芽孢杆菌等)的丰度。这些基因在B6女性中的表达与IL-2Rb、Ccr3和CD80等几个基因的表达呈正相关,这些基因可能与免疫功能有关,如炎症反应和白细胞的迁移。几种细菌的丰度(例如普氏短杆菌等)。和棒状芽孢杆菌(Clostridium ramosum et Rel.)在雄性BALB/c小鼠中表达丰富,与多种免疫功能相关的基因(如APOE、IL-1b和STAT4)的表达呈正相关,如淋巴细胞的增殖和数量。最终的结果是相同的,因为两个品系的小鼠在MLN中表现出相似的性别诱导的免疫细胞群差异。我们的数据表明,微生物区系和肠道免疫群体之间存在性别和菌株特异性的相关性。这些发现可能有助于开发更多针对肠道相关疾病的性别和基因特异性治疗方法。本文的在线版本(10.1186/s13293-018-0186-6)包含向授权用户提供的补充材料。
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. 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. 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. 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. The online version of this article (10.1186/s13293-018-0186-6) contains supplementary material, which is available to authorized users.
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