Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 240E, Los Angeles, CA, 90048, USA.
Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Dig Dis Sci. 2022 Jan;67(1):224-232. doi: 10.1007/s10620-021-06857-y. Epub 2021 Feb 3.
Proton pump inhibitor (PPI) use is extremely common. PPIs have been suggested to affect the gut microbiome, and increase risks of Clostridium difficile infection and small intestinal bacterial overgrowth (SIBO). However, existing data are based on stool analyses and PPIs act on the foregut.
To compare the duodenal and stool microbiomes in PPI and non-PPI users.
Consecutive subjects presenting for upper endoscopy without colonoscopy were recruited. Current antibiotic users were excluded. Subjects taking PPI were age- and gender-matched 1:2 to non-PPI controls. Subjects completed medical history questionnaires, and duodenal aspirates were collected using a validated protected catheter. A subset also provided stool samples. Duodenal and stool microbiomes were analyzed by 16S rRNA sequencing.
The duodenal microbiome exhibited no phylum-level differences between PPI (N = 59) and non-PPI subjects (N = 118), but demonstrated significantly higher relative abundances of families Campylobacteraceae (3.13-fold, FDR P value < 0.01) and Bifidobacteriaceae (2.9-fold, FDR P value < 0.01), and lower relative abundance of Clostridiaceae (88.24-fold, FDR P value < 0.0001), in PPI subjects. SIBO rates were not significantly different between groups, whether defined by culture (> 10 CFU/ml) or 16S sequencing, nor between subjects taking different PPIs. The stool microbiome exhibited significantly higher abundance of family Streptococcaceae (2.14-fold, P = 0.003), and lower Clostridiaceae (2.60-fold, FDR P value = 8.61E-13), in PPI (N = 22) versus non-PPI (N = 47) subjects.
These findings suggest that PPI use is not associated with higher rates of SIBO. Relative abundance of Clostridiaceae was reduced in both the duodenal and stool microbiomes, and Streptococcaceae was increased in stool. The clinical implications of these findings are unknown.
质子泵抑制剂 (PPI) 的使用非常普遍。有研究表明，PPI 会影响肠道微生物群，增加艰难梭菌感染和小肠细菌过度生长 (SIBO) 的风险。然而，现有数据基于粪便分析，并且 PPI 作用于上消化道。
比较 PPI 和非 PPI 使用者的十二指肠和粪便微生物群。
连续招募因上消化道内镜检查而无结肠镜检查的患者。排除当前使用抗生素的患者。PPI 使用者与非 PPI 对照组按年龄和性别 1:2 匹配。患者完成病史问卷，并使用经过验证的保护导管采集十二指肠抽吸物。一部分患者还提供粪便样本。通过 16S rRNA 测序分析十二指肠和粪便微生物群。
PPI 组 (N=59) 和非 PPI 组 (N=118) 的十二指肠微生物群在门水平上没有差异，但 PPI 组的 Campylobacteraceae 科 (3.13 倍，FDR P 值 <0.01) 和 Bifidobacteriaceae 科 (2.9 倍，FDR P 值 <0.01) 的相对丰度显著较高，而 Clostridiaceae 科的相对丰度 (88.24 倍，FDR P 值 <0.0001) 显著较低。无论通过培养 (>10 CFU/ml) 还是 16S 测序定义，两组的 SIBO 发生率均无显著差异，也没有在服用不同 PPI 的患者之间存在差异。PPI 组 (N=22) 的粪便微生物群中，Streptococcaceae 科的丰度显著较高 (2.14 倍，P=0.003)，而 Clostridiaceae 科的丰度显著较低 (2.60 倍，FDR P 值=8.61E-13)，而非 PPI 组 (N=47)。
这些发现表明，PPI 使用与更高的 SIBO 发生率无关。Clostridiaceae 的相对丰度在十二指肠和粪便微生物群中均降低，而 Streptococcaceae 在粪便中增加。这些发现的临床意义尚不清楚。
