Altered Diversity and Composition of Gut Microbiota in Wilson's disease

Cai, Xiangsheng; Deng, Lin; Ma, Xiaogui; Guo, Yusheng; Feng, Zhiting; Liu, Minqi; Guan, Yubin; Huang, Yan-ting; Deng, Jianxin; Li, Hongwei; Sang, Hong; Liu, Fang; Yang, Xiaorong

doi:10.21203/rs.2.24572/v1

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…Patients being treated with zinc sulfate had a higher risk for developing gastric injury. Gut microbial dysbiosis also has been reported in WD 109 . The significance of this finding will require further study.…”

Section: Disorders With Gi/movement Overlapmentioning

confidence: 76%

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Movement Disorders and the Gut: A Review

Talman

Pfeiffer

2022

Movement Disord Clin Pract

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There is a close link between multiple movement disorders and gastrointestinal dysfunction. Gastrointestinal symptoms may precede the development of the neurologic syndrome or may arise following the neurologic presentation. This review will provide an overview of gastrointestinal accompaniments to several well‐known as well as lesser known movement disorders. It will also highlight several disorders which may not be considered primary movement disorders but have an overlapping presentation of both gastrointestinal and movement abnormalities.

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Section: Disorders With Gi/movement Overlapmentioning

confidence: 76%

“…Gut microbial dysbiosis also has been reported in WD. 109 The significance of this finding will require further study.…”

Section: Wilson's Diseasementioning

confidence: 95%

Movement Disorders and the Gut: A Review

Talman

Pfeiffer

2022

Movement Disord Clin Pract

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“…In addition, initial studies in patients with WD indicate reduced alpha diversity of their gut microbiome 11 and our untargeted metabolomic profile in WD revealed a complex metabolic interaction involving dietary and microbiome-derived metabolites or metabolites for which plasma levels are affected by microbiome composition 9 .…”

Section: Introductionmentioning

confidence: 96%

The role of intestine in metabolic dysregulation in murine Wilson disease

Sarode

Mazi

Neier

et al. 2023

Preprint

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Background and aims: Major clinical manifestations of Wilson disease (WD) are related to copper accumulation in the liver and the brain, and little is known about other tissues involvement in metabolic changes in WD. In vitro studies suggested that the loss of intestinal ATP7B could contribute to metabolic dysregulation in WD. We tested this hypothesis by evaluating gut microbiota and lipidome in two mouse models of WD and by characterizing a new mouse model with a targeted deletion of Atp7b in intestine. Methods: Cecal content 16S sequencing and untargeted hepatic and plasma lipidome analyses in the Jackson Laboratory toxic-milk and the Atp7b null global knockout mouse models of WD were profiled and integrated. Intestine-specific Atp7b knockout mice (Atp7bΔIEC) was generated using B6.Cg-Tg(Vil1-cre)997Gum/J mice and Atp7bLox/Lox mice, and characterized using targeted lipidome analysis following a high-fat diet challenge. Results: Gut microbiota diversity was reduced in animal models of WD. Comparative prediction analysis revealed amino acid, carbohydrate, and lipid metabolism functions to be dysregulated in the WD gut microbial metagenome. Liver and plasma lipidomic profiles showed dysregulated tri- and diglyceride, phospholipid, and sphingolipid metabolism in WD models. When challenged with a high-fat diet, Atp7bΔIEC mice exhibited profound alterations to fatty acid desaturation and sphingolipid metabolism pathways as well as altered APOB48 distribution in intestinal epithelial cells. Conclusion: Coordinated changes of gut microbiome and lipidome analyses underlie systemic metabolic manifestations in murine WD. Intestine-specific ATP7B deficiency affected both intestinal and systemic response to a high-fat challenge. WD is a systemic disease in which intestinal-specific ATP7B loss and diet influence phenotypic presentations. Keywords: Wilson disease; copper; gut microbiota; lipid metabolism

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Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome

Durán¹,

Ciucci²,

Palladini

et al. 2021

Nat Commun

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The stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of drugs such as proton pump inhibitors (PPIs), or bacterial infection such as Helicobacter pylori, cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in early phase and rely principally on linear techniques for multivariate analysis. Here we disclose the importance of complementing linear dimensionality reduction techniques with nonlinear ones to unveil hidden patterns that remain unseen by linear embedding. Then, we prove the advantages to complete multivariate pattern analysis with differential network analysis, to reveal mechanisms of bacterial network re-organizations which emerge from perturbations induced by a medical treatment (PPIs) or an infectious state (H. pylori). Finally, we show how to build bacteria-metabolite multilayer networks that can deepen our understanding of the metabolite pathways significantly associated to the perturbed microbial communities.

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Altered Diversity and Composition of Gut Microbiota in Wilson's disease

Cited by 3 publications

References 26 publications

Movement Disorders and the Gut: A Review

Movement Disorders and the Gut: A Review

The role of intestine in metabolic dysregulation in murine Wilson disease

Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome

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