Gut microbial profile in biliary atresia: a case‐control study

Wang, Junfeng; Tian, Qing; Jiang, Jingying; Yang, Yifan; Shen, Zhen; Huang, Yanlei; Chen, Gong; Zheng, Shan; Dong, Rui

doi:10.1111/jgh.14777

Cited by 42 publications

(50 citation statements)

References 35 publications

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“…In this study, the alpha diversity between BA patients and controls was comparable. Wang et al ( 11 ), who included 34 BA patients and 34 controls, have previously showed that alpha diversity in BA patients was significantly lower compared with that of controls. It might be that our sample size was too small to detect such significant differences.…”

Section: Discussionmentioning

confidence: 99%

“…The composition of the microbiota differed significantly: BA was associated with lower abundances of Actinobacteria (eg, Bifidobacteriaceae), the family Lachnospiraceae and greater abundances of Firmicutes (eg, Streptococcaceae), 3 families, which had been associated with BA previously ( 11 ). Bifidobacteriaceae, such as Bifidobacterium longum and Bifidobacterium adolescentis, are abundant anaerobic bacteria in the microbiota of healthy infants ( 15 , 16 ).…”

Section: Discussionmentioning

confidence: 99%

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Gut Microbiota Composition of Biliary Atresia Patients Before Kasai Portoenterostomy Associates With Long-term Outcome

Wessel

Nomden²,

Bruggink³

et al. 2021

Journal of Pediatric Gastroenterology &Amp; Nutrition

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Background and Aims: Biliary atresia (BA) is a cholestatic, fibro-obliterative cholangiopathy of unknown etiology. BA is primarily treated by a surgical approach, that is, the Kasai portoenterostomy (KPE), to obtain clearance of jaundice (COJ). The gut microbiota (GM) composition has been associated with the course of several cholestatic liver diseases. It is largely unknown, however, whether GM composition associates with the outcome of KPE. We compared the GM composition of BA patients and controls and assessed if GM composition before KPE was related to COJ after KPE. Methods: We compared feces of term-born BA patients before KPE and controls (patients undergoing inguinal hernia repair) by 16S rRNA sequencing. Composition and alpha diversity of the GM were compared between BA and controls before KPE and after KPE, between patients with COJ versus without COJ (total serum bilirubin < or ≥20 μmol/L <6 months post-KPE). Results: Alpha diversity was comparable between BA (n = 12, age 1.6 [1.3–1.8] months) and controls (n = 6, age 2.0 [1.4–2.1] months; P = 0.22). Compared with controls, BA patients had lower abundances of Bifidobacteriaceae (β = −1.98, P < 0.001) and Lachnospiraceae (β = −1.84, P = 0.007), and higher abundances of Streptococcus (β = −1.13, P = 0.003). The alpha diversity before KPE correlated negatively with COJ ( R = −0.63, P = 0.03). Lower alpha diversity pre-KPE was associated with COJ [+] (β logit = −0.64, P = 0.04). We observed greater abundances of genus Acinetobacter (β = 1.27, P = 0.03) and family Clostridiaceae (β = 1.45, P = 0.03) and lower abundances of the family Enterobacteriaceae (genera Klebsiella (β = −1.21, P = 0.01), Salmonella (β = −1.57, P = 0.02)) in COJ [+] versus COJ [−]. Conclusions: The GM of BA patients before Kasai portoenterostomy associates with outcome, clearance of jaundice, suggestive of predictive, and mechanistic roles of the gut microbiota composition in bile homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Composition of Biliary Atresia Patients Before Kasai Portoenterostomy Associates With Long-term Outcome

Wessel

Nomden²,

Bruggink³

et al. 2021

Journal of Pediatric Gastroenterology &Amp; Nutrition

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“…This is termed the gut-liver axis. The gut-liver axis has also been investigated in BA (145). As MMP- 7 has not yet been identified in human intestinal Paneth cells, we will not discuss MMP-7 and the gut-liver axis in relation to BA here.…”

Section: Inflammation and Angiogenesismentioning

confidence: 99%

Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

et al. 2020

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Biliary atresia (BA) is a rare cholangiopathy of infancy in which the bile ducts obliterate, leading to profound cholestasis and liver fibrosis. BA is hypothesized to be caused by a viral insult that leads to over-activation of the immune system. Patients with BA are surgically treated with a Kasai portoenterostomy (KPE), which aims to restore bile flow from the liver to the intestines. After KPE, progressive liver fibrosis is often observed in BA patients, even despite surgical success and clearance of their jaundice. The innate immune response is involved during the initial damage to the cholangiocytes and further differentiation of the adaptive immune response into a T-helper 1 cell (Th1) response. Multiple studies have shown that there is continuing elevation of involved cytokines that can lead to the progressive liver fibrosis. However, the mechanism by which the progressive injury occurs is not fully elucidated. Recently, matrix metalloproteinase-7 (MMP-7) has been investigated to be used as a biomarker to diagnose BA. MMPs are involved in extracellular matrix (ECM) turnover, but also have non-ECM related functions. The role of MMP-7 and other MMPs in liver fibrosis is just starting to be elucidated. Multiple studies have shown that serum MMP-7 measurements are able to accurately diagnose BA in a cohort of cholestatic patients while hepatic MMP-7 expression correlated with BA-related liver fibrosis. While the mechanism by which MMP-7 can be involved in the pathophysiology of BA is unclear, MMP-7 has been investigated in other fibrotic pathologies such as renal and idiopathic pulmonary fibrosis. MMP-7 is involved in Wnt/β-catenin signaling, reducing cell-to-cell contact by shedding of E-cadherin, amplifying inflammation and fibrosis via osteopontin (OPN) and TNF-α while it also appears to play a role in induction of angiogenesis This review aims to describe the current understandings of the pathophysiology of BA. Subsequently, we describe how MMP-7 is involved in other pathologies, such as renal and pulmonary fibrosis. Then, we propose how MMP-7 can potentially be involved in BA. By doing this, we aim to describe the putative role of MMP-7 as a prognostic biomarker in BA and to provide possible new therapeutic and research targets that can be investigated in the future.

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“…Pediatric patients with end-stage liver diseases, such as due to biliary atresia or other cholestatic diseases, often have an altered microbial composition (Guo et al 2018;Wang et al 2020a;Wang et al 2019). Such alteration in the microbiome would possibly lead to gut barrier disruption, to bacterial translocation and to triggering of the host's immune and metabolic responses in the liver (De Minicis et al 2014;Fouts et al 2012).…”

Section: Altered Microbial Composition/function In Patients Undergoing Ltmentioning

confidence: 99%

“…Such alteration in the microbiome would possibly lead to gut barrier disruption, to bacterial translocation and to triggering of the host's immune and metabolic responses in the liver (De Minicis et al 2014;Fouts et al 2012). For instance, infants with biliary atresia have lower microbial diversity and higher intestinal permeability than healthy infants (Wang et al 2020a). In particular, patients showed a decrease in the relative abundance of genera which are considered beneficial, i.e., Bifidobacterium and Faecalibacterium (Guo et al 2018;Wang et al 2019), as well as an imbalance in the components of bile acids (Wang et al 2019).…”

Section: Altered Microbial Composition/function In Patients Undergoing Ltmentioning

confidence: 99%

The role of the gut microbiome in graft fibrosis after pediatric liver transplantation

Qin

Verkade

2020

Hum Genet

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Liver transplantation (LT) is a life-saving option for children with end-stage liver disease. However, about 50% of patients develop graft fibrosis in 1 year after LT, with normal liver function. Graft fibrosis may progress to cirrhosis, resulting in graft dysfunction and ultimately the need for re-transplantation. Previous studies have identified various risk factors for the post-LT fibrogenesis, however, to date, neither of the factors seems to fully explain the cause of graft fibrosis. Recently, evidence has accumulated on the important role of the gut microbiome in outcomes after solid organ transplantation. As an altered microbiome is present in pediatric patients with end-stage liver diseases, we hypothesize that the persisting alterations in microbial composition or function contribute to the development of graft fibrosis, for example by bacteria translocation due to increased intestinal permeability, imbalanced bile acids metabolism, and/or decreased production of short-chain fatty acids (SCFAs). Subsequently, an immune response can be activated in the graft, together with the stimulation of fibrogenesis. Here we review current knowledge about the potential mechanisms by which alterations in microbial composition or function may lead to graft fibrosis in pediatric LT and we provide prospective views on the efficacy of gut microbiome manipulation as a therapeutic target to alleviate the graft fibrosis and to improve long-term survival after LT.

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Gut microbial profile in biliary atresia: a case‐control study

Cited by 42 publications

References 35 publications

Gut Microbiota Composition of Biliary Atresia Patients Before Kasai Portoenterostomy Associates With Long-term Outcome

Gut Microbiota Composition of Biliary Atresia Patients Before Kasai Portoenterostomy Associates With Long-term Outcome

Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

The role of the gut microbiome in graft fibrosis after pediatric liver transplantation

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