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对怀孕的非肥胖糖尿病小鼠进行抗生素治疗会导致其后代肠道微生物群改变和肠道免疫变化。

Antibiotic treatment of pregnant non-obese diabetic mice leads to altered gut microbiota and intestinal immunological changes in the offspring.

作者信息

Tormo-Badia N, Håkansson Å, Vasudevan K, Molin G, Ahrné S, Cilio C M

机构信息

Department of Clinical Sciences, Cellular Autoimmunity Unit, Lund University, Skåne University Hospital, Malmö, Sweden.

出版信息

Scand J Immunol. 2014 Oct;80(4):250-60. doi: 10.1111/sji.12205.

Abstract

The intestinal microbiota is important for tolerance induction through mucosal immunological responses. The composition of the gut microbiota of an infant is affected by environmental factors such as diet, disease and antibiotic treatment. However, already in utero, these environmental factors can affect the immunological development of the foetus and influence the future gut microbiota of the infant. To investigate the effects of antibiotic treatment of pregnant mothers on the offspring's gut microbiome and diabetes development, we treated non-obese diabetic (NOD) mice with a cocktail of antibiotics during gestation and the composition of the gut microbiota, diabetes incidence and major gut-related T lymphocyte populations were investigated in the offspring. We observed a persistent reduction in the general diversity of the gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. In addition, by clustering the present bacterial taxa with principal component analysis, we found a differential clustering of gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. Offspring from NOD mothers treated with antibiotics during gestation also showed some immunological alterations in the gut immune system, which could be related to the diversity of the gut microbiome and influence modulation of diabetes development at 20 weeks. Our data point out maternal derangement of the intestinal microbiota as a potential environmental risk factor for T1D development.

摘要

肠道微生物群对于通过黏膜免疫反应诱导耐受性至关重要。婴儿肠道微生物群的组成会受到饮食、疾病和抗生素治疗等环境因素的影响。然而,在子宫内时,这些环境因素就会影响胎儿的免疫发育,并影响婴儿未来的肠道微生物群。为了研究对怀孕母亲进行抗生素治疗对后代肠道微生物组和糖尿病发展的影响,我们在妊娠期间用抗生素鸡尾酒治疗非肥胖糖尿病(NOD)小鼠,并对后代的肠道微生物群组成、糖尿病发病率和主要肠道相关T淋巴细胞群体进行了研究。我们观察到,与对照母亲的后代相比,在妊娠期间接受抗生素治疗的NOD母亲的后代中,肠道微生物群的总体多样性持续降低。此外,通过主成分分析对当前细菌分类群进行聚类,我们发现与对照母亲的后代相比,在妊娠期间接受抗生素治疗的NOD母亲的后代中,肠道微生物群存在差异聚类。在妊娠期间接受抗生素治疗的NOD母亲的后代在肠道免疫系统中也表现出一些免疫改变,这可能与肠道微生物组的多样性有关,并影响20周时糖尿病的发展调节。我们的数据指出,母亲肠道微生物群的紊乱是1型糖尿病发展的潜在环境风险因素。

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