Section of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Pediatr Res. 2023 Feb;93(3):535-540. doi: 10.1038/s41390-022-02149-x. Epub 2022 Jun 14.
The increasing incidence of inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis) around the world has coincided with a wide array of environmental and epidemiologic changes. The relationship between IBD incidence and household or family size decline, however, has not been examined before. Our background epidemiological analyses suggested an inverse association between household size and IBD incidence. We aimed to examine this further in a murine model.
We designed a unique two-generation cohousing model of family size and IBD susceptibility in C57BL/6J mice. Serial fecal microbiomes during cohousing were examined by high-throughput 16S rRNA sequencing. After cohousing for 10 days, mice were exposed to dextran sulfate sodium (DSS) to induce acute colitis. Body weight as a significant correlate of colitis severity was measured.
Mice in a large household arrangement demonstrated less weight loss than mice in the small household arrangement in the DSS model. Age- and housing-dependent microbiome shifts were found.
Larger households may be protective against intestinal inflammation through intergenerational microbiome modulation. Our observations may set the foundation for age-dependent, microbiome-directed future prevention against IBD.
Epidemiological analyses in this study suggested that IBD incidence may inversely correlate with household size (an indicator of family size/children per family), which has not been examined before. A uniquely designed two-generation cohousing model of family size and IBD susceptibility in mice supported our epidemiologic observations. Microbiome changes in our cohousing model may set the foundation for age-dependent, microbiome-directed prevention against IBD.
炎症性肠病（IBD：克罗恩病和溃疡性结肠炎）在全球范围内的发病率不断上升，同时也伴随着一系列环境和流行病学变化。然而，IBD 的发病率与家庭规模或家庭中儿童数量减少之间的关系尚未得到研究。我们之前的背景流行病学分析表明，家庭规模与 IBD 发病率之间存在反比关系。我们旨在进一步在小鼠模型中研究这一问题。
我们设计了一种独特的两代同堂共居的家庭规模和 IBD 易感性的小鼠模型。通过高通量 16S rRNA 测序对共居期间的粪便微生物组进行了研究。共居 10 天后，小鼠接受葡聚糖硫酸钠（DSS）诱导急性结肠炎。体重作为结肠炎严重程度的重要相关指标进行了测量。
在 DSS 模型中，大家庭安排的小鼠比小家庭安排的小鼠体重减轻更少。发现了与年龄和住房相关的微生物组变化。
较大的家庭可能通过代际微生物组调节对肠道炎症具有保护作用。我们的观察结果可能为针对 IBD 的依赖年龄、依赖微生物组的未来预防措施奠定基础。
本研究的流行病学分析表明，IBD 的发病率可能与家庭规模（家庭大小/每个家庭的儿童数量的指标）呈反比关系，这尚未得到研究。一种独特的设计的大小家庭和小鼠 IBD 易感性的两代同堂共居模型支持了我们的流行病学观察。我们的共居模型中的微生物组变化可能为依赖年龄、依赖微生物组的预防 IBD 奠定基础。
