The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
Translational Research Institute, Brisbane, Queensland, Australia.
Diabetes Care. 2018 Oct;41(10):2178-2186. doi: 10.2337/dc18-0777. Epub 2018 Aug 12.
Dysbiosis of the gut microbiota has been linked to disease pathogenesis in type 1 diabetes, yet the functional consequences to the host of this dysbiosis are unknown. We investigated the functional interactions between the microbiota and the host associated with type 1 diabetes disease risk.
We performed a cross-sectional analysis of stool samples from subjects with recent-onset type 1 diabetes ( = 33), islet autoantibody-positive subjects ( = 17), low-risk autoantibody-negative subjects ( = 29), and healthy subjects ( = 22). Metaproteomic analysis was used to identify gut- and pancreas-derived host and microbial proteins, and these data were integrated with sequencing-based microbiota profiling.
Both human (host-derived) proteins and microbial-derived proteins could be used to differentiate new-onset and islet autoantibody-positive subjects from low-risk subjects. Significant alterations were identified in the prevalence of host proteins associated with exocrine pancreas output, inflammation, and mucosal function. Integrative analysis showed that microbial taxa associated with host proteins involved in maintaining function of the mucous barrier, microvilli adhesion, and exocrine pancreas were depleted in patients with new-onset type 1 diabetes.
These data support that patients with type 1 diabetes have increased intestinal inflammation and decreased barrier function. They also confirmed that pancreatic exocrine dysfunction occurs in new-onset type 1 diabetes and show for the first time that this dysfunction is present in high-risk individuals before disease onset. The data identify a unique type 1 diabetes-associated signature in stool that may be useful as a means to monitor disease progression or response to therapies aimed at restoring a healthy microbiota.
肠道微生物群落失调与 1 型糖尿病的发病机制有关，但这种失调对宿主的功能后果尚不清楚。我们研究了与 1 型糖尿病疾病风险相关的微生物群和宿主之间的功能相互作用。
我们对近期诊断为 1 型糖尿病的患者（n=33）、胰岛自身抗体阳性的患者（n=17）、低风险自身抗体阴性的患者（n=29）和健康对照者（n=22）的粪便样本进行了横断面分析。采用代谢蛋白质组学分析方法鉴定肠道和胰腺来源的宿主和微生物蛋白，并将这些数据与基于测序的微生物群分析进行整合。
人类（宿主来源）蛋白和微生物衍生蛋白均可用于区分新发和胰岛自身抗体阳性患者与低风险患者。与外分泌胰腺输出、炎症和黏膜功能相关的宿主蛋白的流行率发生了显著改变。综合分析显示，与参与维持黏液屏障、微绒毛黏附和外分泌胰腺功能的宿主蛋白相关的微生物类群在新诊断的 1 型糖尿病患者中减少。
这些数据支持 1 型糖尿病患者存在肠道炎症增加和屏障功能下降的情况。它们还证实了新诊断的 1 型糖尿病患者存在胰腺外分泌功能障碍，并首次表明这种功能障碍在疾病发作前的高危人群中就存在。这些数据在粪便中确定了一种独特的 1 型糖尿病相关特征，可能有助于监测疾病进展或对旨在恢复健康微生物群的治疗反应。
