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在乳糜泻患儿中使用双歧杆菌菌株进行临床干预揭示了 TNF-α 和短链脂肪酸的新型微生物调节剂。

Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and short-chain fatty acids.

机构信息

Department of Microbiology, Biochemistry, Molecular Biology and Biotechnology, Faculty of Agriculture and Life Sciences, University of Maribor, Pivola 10, 2311 Hoče, Slovenia.

Department of Pediatrics, University Clinical Center Maribor, Ljubljanska ulica 5, 2000 Maribor, Slovenia.

出版信息

Clin Nutr. 2019 Jun;38(3):1373-1381. doi: 10.1016/j.clnu.2018.06.931. Epub 2018 Jun 18.

DOI:10.1016/j.clnu.2018.06.931
PMID:29960810
Abstract

BACKGROUND & AIMS: Celiac disease (CD) is an immune-mediated systemic disease, caused by ingestion of gluten in genetically predisposed individuals. Gut microbiota dysbiosis might play a significant role in pathogenesis of chronic enteropathies and its modulation can be used as an intervention strategy in CD as well. In this study, we aimed to identify correlations between fecal microbiota, serum tumor necrosis factor alpha (TNF-α) and fecal short-chain fatty acids (SCFAs) in healthy children and children with CD after administration of probiotic Bifidobacterium breve BR03 and B632.

METHODS

A double-blind placebo-controlled study enrolled 40 children with CD (CD) and 16 healthy children (HC). CD children were randomly allocated into two groups, of which 20 belonged to the placebo (PL) group and 20 to the Probiotic (PR) group. The PR group received a probiotic formulation containing a mixture of 2 strains, B. breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) in 1:1 ratio for 3 months. Subsequently, for statistical analysis, blood and fecal samples from CD children (on enrolment - T0 and after 3 months, at the end of intervention with probiotic/placebo - T1) and HC children were used. The HC group was sampled only once (T0).

RESULTS

Verrucomicrobia, Parcubacteria and some yet unknown phyla of Bacteria and Archaea may be involved in the disease, indicated by a strong correlation to TNF-α. Likewise, Proteobacteria strongly correlated with fecal SCFAs concentration. The effect of probiotic administration has disclosed a negative correlation between Verrucomicrobia, some unknown phyla of Bacteria, Synergistetes, Euryarchaeota and some SCFAs, turning them into an important target in microbiome restoration process. Synergistetes and Euryarchaeota may have a role in the anti-inflammatory process in healthy human gut.

CONCLUSIONS

Our results highlight new phyla, which may have an important relation to disease-related parameters, CD itself and health.

摘要

背景与目的

乳糜泻(CD)是一种由遗传易感性个体摄入麸质引起的免疫介导的系统性疾病。肠道微生物失调可能在慢性肠病的发病机制中起重要作用,其调节也可以作为 CD 的一种干预策略。本研究旨在确定健康儿童和 CD 儿童在服用短双歧杆菌 BR03 和 B632 益生菌后粪便微生物群、血清肿瘤坏死因子-α(TNF-α)和粪便短链脂肪酸(SCFA)之间的相关性。

方法

这项双盲安慰剂对照研究纳入了 40 名 CD 儿童(CD)和 16 名健康儿童(HC)。CD 儿童随机分为两组,其中 20 名属于安慰剂(PL)组,20 名属于益生菌(PR)组。PR 组接受含有 2 株混合的益生菌制剂,即短双歧杆菌 BR03(DSM 16604)和短双歧杆菌 B632(DSM 24706),比例为 1:1,持续 3 个月。随后,为了进行统计分析,使用 CD 儿童(入组时-T0 和干预结束时,即服用益生菌/安慰剂 3 个月后-T1)和 HC 儿童的血液和粪便样本。HC 组仅采样一次(T0)。

结果

疣微菌门、 parcubacteria 和一些未知的细菌和古菌门可能与疾病有关,这与 TNF-α 呈强烈相关。同样,变形菌门与粪便 SCFA 浓度呈强烈相关。益生菌给药的作用揭示了疣微菌门、一些未知的细菌门、互养菌门、古菌门和一些 SCFA 之间的负相关,使它们成为微生物组恢复过程中的一个重要目标。互养菌门和古菌门可能在健康人肠道的抗炎过程中发挥作用。

结论

我们的研究结果强调了新的菌群,它们可能与疾病相关参数、CD 本身和健康有重要关系。

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