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The profile of blood microbiome in new-onset type 1 diabetes children.

ABSTRACT: Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome were identified by random forest analysis, providing strong discriminatory power for T1D with an AUC of 0.82. PICRUSt analysis suggested that bacteria capable of inducing inflammation were more likely to enter the bloodstream in T1D. The overlap of the gut and oral microbiome with the blood microbiome implied potential translocation of bacteria from the gut and oral cavity to the bloodstream. Our study raised the necessity of further mechanistic investigations into the roles of blood microbiome in T1D.

SUBMITTER: Yuan X

PROVIDER: S-EPMC11255850 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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The profile of blood microbiome in new-onset type 1 diabetes children.

Yuan Xiaoxiao X Yang Xin X Xu Zhenran Z Li Jie J Sun ChengJun C Chen Ruimin R Wei Haiyan H Chen Linqi L Du Hongwei H Li Guimei G Yang Yu Y Chen Xiaojuan X Cui Lanwei L Fu Junfen J Wu Jin J Chen Zhihong Z Fang Xin X Su Zhe Z Zhang Miaoying M Wu Jing J Chen Xin X Zhou Jiawei J Luo Yue Y Zhang Lei L Wang Ruirui R Luo Feihong F

iScience 20240612 7

Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome ...[more]

PMID: 39027370

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Project description:AimScreening for coeliac disease in asymptomatic children with new-onset type 1 diabetes is controversial. The aim of this study was to analyse whether the confirmation of coeliac disease in children with new-onset type 1 diabetes and positive screening results can be postponed.MethodsThis was a multicentre population-based cohort study based on the German/Austrian/Swiss/Luxembourgian Prospective Diabetes Follow-up Registry (Diabetes Patienten Verlaufsdokumentation [DPV]). Participants aged ≤18 years diagnosed with type 1 diabetes between 1995 and June 2021 and with elevated IgA tissue transglutaminase antibodies (anti-tTGA) at diabetes onset on screening for coeliac disease were included. We compared outcomes of participants with a diabetes duration of more than 1 year between those in whom coeliac disease was confirmed histologically within the first 6 months and those in whom coeliac disease was confirmed between 6 and 36 months after diabetes diagnosis.ResultsOf 92,278 children and adolescents with a diagnosis of type 1 diabetes, 26,952 (29.2%) had documented anti-tTGA data at diabetes onset. Of these, 2340 (8.7%) had an elevated anti-tTGA level. Individuals who screened positive were younger (median age 9.0 vs 9.8 years, p<0.001) and more often female (53.1% vs 44.4%, p<0.001). A total of 533 participants (22.8% of those who screened positive) had a documented biopsy, of whom 444 had documented histological confirmation of coeliac disease. Of 411 participants with biopsy-proven coeliac disease within the first 36 months of diabetes and follow-up data, histological confirmation was performed in 264 (64.2%) within the first 6 months and in 147 (35.8%) between 6 and 36 months after diabetes onset. At follow-up (median diabetes duration 5.3 years and 5.1 years, respectively), estimated median HbA1c levels (62.8 mmol/mol vs 62.2 mmol/mol [7.9% vs 7.8%]), cardiovascular risk markers (lipids, rate of microalbuminuria, blood pressure), rates of acute diabetes complications (diabetic ketoacidosis, severe hypoglycaemia) and the proportions of participants reaching anti-tTGA levels within the normal range did not differ between groups. Participants with delayed histological confirmation of coeliac disease showed no negative effects on growth or weight gain during the observation period.ConclusionsOur study suggests that the histological confirmation of coeliac disease in asymptomatic individuals with new-onset type 1 diabetes could be postponed.

Project description:BackgroundBlood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.MethodsWe performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of follow-up in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons.Findings145 939 participants (88 500 [60·6%] men and 57 429 [39·4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4·5 years (IQR 2·0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0·89 [95% CI 0·84-0·95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0·84 [95% 0·76-0·93]) and angiotensin II receptor blockers (RR 0·84 [0·76-0·92]) reduced the risk of new-onset type 2 diabetes; however, the use of β blockers (RR 1·48 [1·27-1·72]) and thiazide diuretics (RR 1·20 [1·07-1·35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1·02 [0·92-1·13]).InterpretationBlood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes.FundingBritish Heart Foundation, National Institute for Health Research, and Oxford Martin School.

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The profile of blood microbiome in new-onset type 1 diabetes children.

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The profile of blood microbiome in new-onset type 1 diabetes children.

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