Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis

被引：61

作者：

Bajaj, Jasmohan S. ^{[1
,2
]}

Salzman, Nita ^{[3
]}

Acharya, Chathur ^{[1
,2
]}

Takei, Hajime ^{[4
]}

Kakiyama, Genta ^{[1
,2
]}

Fagan, Andrew ^{[1
,2
]}

White, Melanie B. ^{[1
,2
]}

Gavis, Edith A. ^{[1
,2
]}

Holtz, Mary L. ^{[3
]}

Hayward, Michael ^{[3
]}

Nittono, Hiroshi ^{[4
]}

Hylemon, Phillip B. ^{[2
,5
]}

Cox, I. Jane ^{[6
]}

Williams, Roger ^{[6
]}

Taylor-Robinson, Simon D. ^{[7
]}

Sterling, Richard K. ^{[1
,2
]}

Matherly, Scott C. ^{[1
,2
]}

Fuchs, Michael ^{[1
,2
]}

Lee, Hannah ^{[1
,2
]}

Puri, Puneet ^{[1
,2
]}

Stravitz, R. Todd ^{[1
,2
]}

Sanyal, Arun J. ^{[1
,2
]}

Ajayi, Lola ^{[6
]}

Le Guennec, Adrien ^{[8
,9
]}

Atkinson, R. Andrew ^{[8
,9
]}

Siddiqui, Mohammad S. ^{[1
,2
]}

Luketic, Velimir ^{[1
,2
]}

Pandak, William M. ^{[1
,2
]}

Sikaroodi, Masoumeh ^{[10
]}

Gillevet, Patrick M. ^{[10
]}

机构：

[1] Virginia Commonwealth Univ, Div Gastroenterol Hepatol & Nutr, 1201 Broad Rock Blvd, Richmond, VA 23249 USA

[2] McGuire VA Med Ctr, 1201 Broad Rock Blvd, Richmond, VA 23249 USA

[3] Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA

[4] Junshin Clin Bile Acid Inst, Meguro Ku, Tokyo, Japan

[5] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23249 USA

[6] Fdn Liver Res, Inst Hepatol London, London, England

[7] Imperial Coll London, Dept Surg & Canc, London, England

[8] Kings Coll London, Randall Ctr Cell & Mol Biophys, London, England

[9] Kings Coll London, Ctr Biomol Spect, London, England

[10] George Mason Univ, Microbiome Anal Ctr, Manassas, VA USA

来源：

JCI INSIGHT | 2019年 / 4卷 / 24期

基金：

英国惠康基金;

关键词：

BILE-ACID PROFILE; SPECTROSCOPY;

D O I：

10.1172/jci.insight.133410

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

BACKGROUND. Hepatic encephalopathy (HE) is associated with poor outcomes. A prior randomized, pilot trial demonstrated safety after oral capsular fecal microbial transplant (FMT) in HE, with favorable changes in microbial composition and cognition. However, microbial functional changes are unclear. The aim of this study was to determine the effect of FMT on the gut-brain axis compared with placebo, using microbial function based on bile acids (BAs), inflammation (serum IL-6, LPS-binding protein [LBP]), and their association with EncephalApp. METHODS. Twenty cirrhotic patients were randomized 1:1 into groups that received 1-time FMT capsules from a donor enriched in Lachnospiraceae and Ruminococcaceae or placebo capsules, with 5-month follow-up for safety outcomes. Stool microbiota and BA; serum IL-6, BA, and LBP; and EncephalApp were analyzed at baseline and 4 weeks after FMT/placebo. Correlation networks among microbiota, BAs, EncephalApp, IL-6, and LBP were performed before/after FMT. RESULTS. FMT-assigned participants had 1 HE recurrence and 2 unrelated infections. Six placebo-assigned participants developed negative outcomes. FMT, but not placebo, was associated with reduced serum IL-6 and LBP and improved EncephalApp. FMT-assigned participants demonstrated higher deconjugation and secondary BA formation in feces and serum compared with baseline. No change was seen in placebo. Correlation networks showed greater complexity after FMT compared with baseline. Beneficial taxa, such as Ruminococcaceae, Verrucomicrobiaceae, and Lachnospiraceae, were correlated with cognitive improvement and decrease in inflammation after FMT. Fecal/serum secondary/primary ratios and PiCRUST secondary BA pathways did not increase in participants who developed poor outcomes. CONCLUSION. Gut microbial function in cirrhosis is beneficially affected by capsular FMT, with improved inflammation and cognition. Lower secondary BAs in FMT recipients could select for participants who develop negative outcomes.

引用

页数：11

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