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质子泵抑制剂治疗喉咽反流患者前后唾液微生物群组成的变化:一项自身对照研究。

Salivary microbiota composition before and after use of proton pump inhibitors in patients with laryngopharyngeal reflux: a self-control study.

机构信息

Senior Department of Otolaryngology Head and Neck Surgery, the Sixth Medical Center, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, 100048, China.

State Key Laboratory of Hearing and Balance Science, Beijing, 100853, China.

出版信息

BMC Oral Health. 2024 Oct 8;24(1):1194. doi: 10.1186/s12903-024-05000-3.

Abstract

BACKGROUND

Issues associated with proton pump inhibitor (PPI) usage have been documented. PPIs affect the gastrointestinal microbiome, as well as the saliva microbiota of healthy individuals. However, the alterations in the saliva microbiota of laryngopharyngeal reflux (LPR) patients remain unclear. This study aims to examine the composition of saliva microbiota in LPR patients before and after PPI usage through a self-controlled study.

METHODS

Thirty-two adult LPR patients participated in the study. Saliva samples were collected before and after an 8-week regimen of twice-daily administration of 20-mg esomeprazole. The impact of PPI administration on bacterial communities was assessed using 16 S rRNA gene sequencing. The functional and metabolic changes in saliva microbial communities after PPI usage were analyzed using PICRUSt2 based on our 16 S rRNA gene sequencing results.

RESULTS

The alpha diversity within the salivary microbiota, as measured by the PD-whole-tree index, exhibited a significant difference between samples collected before and after PPI application (P = 0.038). Additionally, PCoA analysis of unweighted UniFrac distances (beta diversity) revealed distinct separation of saliva sample microbiota structures before and after PPI application in LPR patients, with statistical significance (Adonis test, R = 0.063, P< 0.010). Taxon-based analysis indicated that PPI administration increased the abundance of Epsilonproteobacteria, Campylobacterales, Campylobacteraceae, Campylobacter, and Campylobacter_gracilis, while reducing the abundance of Lactobacillaceae and Lactobacillus in salivary samples ( P< 0.050). Using LEfSe to compare bacterial abundances, Bacillaceae and Anoxybacillus were found to be enriched before PPI usage in LPR patients. Furthermore, the proportion of genes responsible for indole alkaloid biosynthesis in the salivary microbiota of LPR patients significantly increased after PPI therapy (P< 0.050).

CONCLUSIONS

These findings indicate that PPIs induce alterations in the salivary microbiota of LPR patients.

CHINESE CLINICAL TRIAL REGISTRY

No. ChiCTR2300067507. Registered on January 10,2023 retrospectively.

摘要

背景

质子泵抑制剂(PPI)使用相关问题已有相关文献记载。PPI 会影响胃肠道微生物群,以及健康个体的唾液微生物群。然而,喉咽反流(LPR)患者唾液微生物群的变化尚不清楚。本研究旨在通过自身对照研究,检测使用质子泵抑制剂(PPI)前后 LPR 患者唾液微生物群的组成。

方法

32 例成年 LPR 患者参与了这项研究。在每天两次服用 20mg 埃索美拉唑 8 周后,采集唾液样本。通过 16S rRNA 基因测序评估 PPI 给药对细菌群落的影响。根据我们的 16S rRNA 基因测序结果,使用 PICRUSt2 分析 PPI 使用后唾液微生物群落的功能和代谢变化。

结果

唾液微生物群内的 alpha 多样性,用 PD-全树指数衡量,在使用 PPI 前后的样本中存在显著差异(P=0.038)。此外,LPR 患者唾液样本微生物群结构的未加权 UniFrac 距离(beta 多样性)的 PCoA 分析显示,在使用 PPI 前后有明显的分离,具有统计学意义(Adonis 检验,R=0.063,P<0.010)。基于分类群的分析表明,PPI 给药增加了 Epsilonproteobacteria、Campylobacterales、Campylobacteraceae、Campylobacter 和 Campylobacter_gracilis 的丰度,同时降低了唾液样本中 Lactobacillaceae 和 Lactobacillus 的丰度(P<0.050)。使用 LEfSe 比较细菌丰度,发现 Bacillaceae 和 Anoxybacillus 在 LPR 患者使用 PPI 前丰度增加。此外,LPR 患者唾液微生物群中吲哚生物碱生物合成相关基因的比例在 PPI 治疗后显著增加(P<0.050)。

结论

这些发现表明,PPI 会引起 LPR 患者唾液微生物群的变化。

临床试验注册

No. ChiCTR2300067507. 于 2023 年 1 月 10 日回顾性注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe52/11460238/b024aa3f475d/12903_2024_5000_Fig1_HTML.jpg

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