Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis.
Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis.
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多种聚焦于黏附和生物膜形成的细菌毒力因子与肝硬化的转归相关。
DOI：
10.1080/19490976.2021.1993584
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发表时间：
2021-01
期刊：
影响因子：
12.2
通讯作者：
Gillevet PM
中科院分区：
文献类型：
--
作者：
Bajaj JS;Shamsaddini A;Acharya C;Fagan A;Sikaroodi M;Gavis E;McGeorge S;Khoruts A;Fuchs M;Sterling RK;Lee H;Gillevet PM
肠道微生物区系改变与肝硬变的不良结局有关，包括感染和肝性脑病(HE)。然而，细菌毒力因子(VFS)的作用尚不清楚。目的：明确VFS与肝硬变严重程度和感染的关系，它们与预后的关系，以及粪便微生物区系移植(FMT)的影响。对照组和肝硬变患者(代偿期、仅HE期、仅腹水期、两者均为感染期)粪便中的VF丰度通过元基因组分析进行了测定。患者被跟踪观察90天的住院时间和1年的死亡。在安慰剂对照的FMT试验之前/之后收集的粪便样本也被分析。比较所有菌种和选定病原菌(大肠埃希菌、克雷伯氏菌、假单胞菌、葡萄球菌、链球菌和肠球菌)的菌种和VF。对临床生物标记物和VFS进行多变量分析以预测结果。分析FMT前后和FMT/安慰剂治疗后VFS的变化。结果：共纳入233例受试者(对照组40例，代偿期43例，单纯肝性脑病30例，单纯腹水20例，两者兼有70例，感染30例)。失代偿患者，特别是感染患者，与其他患者相比，铁载体、生物膜和黏附因子的VFS编码更高。来自肠杆菌科和肠球菌的生物膜和粘附性VFS与死亡和住院无关，与临床因素无关，无论何时分析所有VFS或选定的病原体。与FMT前和安慰剂组相比，FMT组FMT后VF降低。来自多个物种的毒力因子集中在黏附和生物膜上，随着失代偿和感染而增加，与死亡和住院有关，与临床因素无关，并被FMT减弱。专注于多种毒力因子的策略可能会潜在地影响肝硬变的结果。这篇手稿的部分是在2021年虚拟国际肝脏大会上的口头陈述VF：毒力因子，HE：肝性脑病，FMT：粪便微生物区系移植，PPI：质子泵抑制物，LPS：脂多糖，VFDB：毒力因子数据库，OTU：操作分类单位，SBP：自发性细菌性腹膜炎，UTI：尿路感染，MRSA：甲氧西林耐药金黄色葡萄球菌，VRE：万古霉素耐药肠球菌，MAAsLin2：微生物群多变量与线性模型的关联，LPS：脂多糖，AKI：急性肾损伤
Altered gut microbiota is associated with poor outcomes in cirrhosis, including infections and hepatic encephalopathy (HE). However, the role of bacterial virulence factors (VFs) is unclear. Aim: Define association of VFs with cirrhosis severity and infections, their linkage with outcomes, and impact of fecal microbiota transplant (FMT). VF abundances were determined using metagenomic analysis in stools from controls and cirrhosis patients (compensated, HE-only, ascites-only, both and infected). Patients were followed for 90-day hospitalizations and 1-year death. Stool samples collected before/after a placebo-controlled FMT trial were also analyzed. Bacterial species and VFs for all species and selected pathogens (Escherichia, Klebsiella, Pseudomonas, Staphylococcus, Streptococcus, and Enterococcus spp) were compared between groups. Multi-variable analyses were performed for clinical biomarkers and VFs for outcome prediction. Changes in VFs pre/post-FMT and post-FMT/placebo were analyzed. Results: We included 233 subjects (40 controls, 43 compensated, 30 HE-only, 20 ascites-only, 70 both, and 30 infected). Decompensated patients, especially those with infections, had higher VFs coding for siderophores, biofilms, and adhesion factors versus the rest. Biofilm and adhesion VFs from Enterobacteriaceae and Enterococcus spp associated with death and hospitalizations independent of clinical factors regardless of when all VFs or selected pathogens were analyzed. FMT was associated with reduced VF post-FMT versus pre-FMT and post-placebo groups. Virulence factors from multiple species focused on adhesion and biofilms increased with decompensation and infections, associated with death and hospitalizations independent of clinical factors, and were attenuated with FMT. Strategies focused on targeting multiple virulence factors could potentially impact outcomes in cirrhosis. Portions of this manuscript were an oral presentation in the virtual International Liver Congress 2021 VF: virulence factors, HE: hepatic encephalopathy, FMT: Fecal microbiota transplant, PPI: proton pump inhibitors, LPS: lipopolysaccharides, VFDB: Virulence factor database, OTU: operational taxonomic units, SBP: spontaneous bacterial peritonitis, UTI: urinary tract infections, MRSA: methicillin resistant Staphylococcus aureus, VRE: vancomycin-resistant Enterococcus, MAAsLin2: Microbiome Multivariable Associations with Linear Models, LPS: lipopolysaccharides, AKI: acute kidney injury
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DOI：
10.1590/s0074-02762013000500009
发表时间：
2013-08-01
期刊：
Memórias do Instituto Oswaldo Cruz
影响因子：
--
作者：
Comerlato, Carolina Baldisserotto;Resende, Mariah Costa Carvalho de;d'Azevedo, Pedro Alves
通讯作者：
d'Azevedo, Pedro Alves
影响因子：
4.6
作者：
Berry IJ;Widjaja M;Jarocki VM;Steele JR;Padula MP;Djordjevic SP
通讯作者：
Djordjevic SP
影响因子：
4.2
作者：
Dautin N
通讯作者：
Dautin N
影响因子：
3.1
作者：
Adams, C;Pitzer, J;Minion, FC
通讯作者：
Minion, FC
影响因子：
14.9
作者：
Chen L;Yang J;Yu J;Yao Z;Sun L;Shen Y;Jin Q
通讯作者：
Jin Q