Association study of gut flora in Wilson's disease through high-throughput sequencing

Geng, Hao; Shu, Shan; Dong, Jianjian; Li, Hai; Xu, Chenchen; Han, Yongsheng; Hu, Jiyuan; Han, Yongzhu; Yang, Renmin; Cheng, Nan

doi:10.1097/md.0000000000011743

Cited by 23 publications

(22 citation statements)

References 26 publications

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“…Gut microbiota comparison between autism spectrum disorder (ASD) and control groups at the species level. The species with significant richness difference (p < .05, computed by STAMP) between the two groups are shown Megamonas, a harmful bacteria related to Wilson's disease [Geng et al, 2018] and obesity [Kieler et al, 2017]. Similarly to that in previous reports, we also found a significant reduction in the proportion of four genera (Escherichia/Shigella [Strati et al, 2017], Dialister [F. Strati et al, 2017], Haemophilus [Kang et al, 2018], and Flavonifractor [Ma et al, 2019]) in ASD samples compared to in the control.…”

Section: Discussionsupporting

confidence: 87%

Changes in the Gut Microbiota of Children with Autism Spectrum Disorder

Zou

Wang

et al. 2020

Autism Research

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Alterations in the gut microbiota may influence gastrointestinal (GI) dysbiosis frequently reported in individuals with autism spectrum disorder (ASD). In this study, we sequenced the bacterial 16S rRNA gene to evaluate changes in fecal microbiota between 48 children with ASD and 48 healthy children in China. At the phylum level, the number of Firmicutes, Proteobacteria, and Verrucomicrobia decreased in children with ASD, while the Bacteroidetes/Firmicutes was significantly higher in autistic children due to enrichment of Bacteroidetes. At the genus level, the amount of Bacteroides, Prevotella, Lachnospiracea_incertae_sedis, and Megamonas increased, while Clostridium XlVa, Eisenbergiella, Clostridium IV, Flavonifractor, Escherichia/Shigella, Haemophilus, Akkermansia, and Dialister decreased in children with ASD relative to the controls. Significant increase was observed in the number of species synthesizing branched‐chain amino acids (BCAAs), like Bacteroides vulgatus and Prevotella copri, while the numbers of Bacteroides fragilis and Akkermansia muciniphila decreased in children with ASD compared to the controls. Most importantly, the highest levels of pathogenic bacteria were different for each child with ASD in this cohort. We found that only one functional module, cellular antigens, was enriched in children with ASD, and other pathways like lysine degradation and tryptophan metabolism were significantly decreased in children with ASD. These findings provide further evidence of altered gut microbiota in Chinese ASD children and may contribute to the treatment of patients with ASD. Lay Summary This study characterized the gut bacteria composition of 48 children with ASD and 48 neurotypical children in China. The metabolic disruptions caused by altered gut microbiota may contribute significantly to the neurological pathophysiology of ASD, including significant increases in the number of species synthesizing BCAAs, and decreases in the number of probiotic species. These findings suggest that a gut microbiome‐associated therapeutic intervention may provide a novel strategy for treating GI symptoms frequently seen in individuals with ASD. Autism Res 2020, 13: 1614–1625. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 87%

Changes in the Gut Microbiota of Children with Autism Spectrum Disorder

Zou

Wang

et al. 2020

Autism Research

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“…Therefore, the decrease of these two probiotics probably contributes to the disorder of physiological functions as Firmicutes in WD patients. The gut microbiome in the WD group also showed a significantly higher abundances of Proteobacteria and Fusobacteria than healthy individuals, consistent with the results reported by Geng [11]. The opportunistic pathogen of Proteobacteria created a major structural imbalance of gut microbiota in WD patients, while Fusobacteria have been widely recognized for the potential inducer of T regulatory cells or carcinogens promoting autophagy activation [24].…”

Section: Discussionsupporting

confidence: 87%

“…This is the first study to elaborate the detailed feactures of diversity and composition of gut microbiome in WD and explored the possible microbiome-related functions, some results of which were different from the study performed by Geng [11]. Though the two studies both showed an elimination, decreased density and loss of bacterial diversity of the microbial ecosystem in the WD patients, however, some opponent characterizations of the gut microbiome in WD were discovered in this study.…”

Section: Discussionmentioning

confidence: 59%

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

Cai

Deng

et al. 2020

Preprint

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Background: Wilson’s disease (WD) is a rare autosomal recessive inherited disorder of chronic copper toxicosis with high mortality and disability. Recent evidence suggests a correlation between dysbiosis in the gut microbiome and metabolic disease. Therefore, the impact of intestinal microbiota polymorphism in WD need to be explore for seeking some microbiota benefit for WD patients. Methods: In this study, the 16S rRNA sequencing was performed on fecal samples from 14 patients with WD and were compared to the results from 16 healthy individuals. The diversity and composition of the gut microbiome in the WD group were significantly lower than those in healthy individuals. Results: The WD group presented unique richness of Gemellaceae , Pseudomonadaceae and Spirochaetaceae at family level in WD group, which were hardly detected in healthy controls The WD group had a markedly lower abundance of Acidobacteria , Firmicutes and Verrucomicrobia , and a higher abundance of Bacteroidet es, Proteobacteria , Cyanobacteria and Fusobacteria than that in healthy individuals. The Firmicutes to Bacteroidetes ratio in the WD group was significantly lower than that of healthy control. The functional profile of the gut microbiome from WD patients showed a lower abundance of bacterial groups involved in the pathways of transcription factors and ABC-type transporters, compared to healthy individuals. The dysbiosis of gut microbiota may be influenced by the host metabolic disorders of WD such as signaling pathway of ABC-type transporters and multiple metabolic modules. Conclusions: This study provides a new understanding of the pathogenesis of WD and new possible therapeutic targets.

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“…Therefore, depending on the status of microbiota, diverse numbers of aged neutrophils might be available in mice with subchronic copper deficiency and Atp7a mutants, while it is the aged neutrophil phenotype that exhibits enhanced NET formation under inflammatory conditions (70). Although we are unaware of studies on microbiota composition in Menkes disease-affected humans or mice, it is known to be altered in Wilson disease patients (72). Therefore, verification of microbiota changes in Menkes patients and in Wilson and Menkes mice could shed light on this issue.…”

Section: Discussionmentioning

confidence: 99%

Reduced Neutrophil Extracellular Trap (NET) Formation During Systemic Inflammation in Mice With Menkes Disease and Wilson Disease: Copper Requirement for NET Release

et al. 2020

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Neutrophil extracellular traps (NETs) contribute to pathological disorders, and their release was directly linked to numerous diseases. With intravital microscopy (IVM), we showed previously that NETs also contribute to the pathology of systemic inflammation and are strongly deposited in liver sinusoids. Over a decade since NET discovery, still not much is known about the metabolic or microenvironmental aspects of their formation. Copper is a vital trace element essential for many biological processes, albeit its excess is potentially cytotoxic; thus, copper levels are tightly controlled by factors such as copper transporting ATPases, ATP7A, and ATP7B. By employing IVM, we studied the impact of copper on NET formation during endotoxemia in liver vasculature on two mice models of copper excess or deficiency, Wilson (ATP7B mutants) and Menkes (ATP7A mutants) diseases, respectively. Here, we show that respective ATP7 mutations lead to diminished NET release during systemic inflammation despite unaltered intrinsic capacity of neutrophils to cast NETs as tested ex vivo. In Menkes disease mice, the in vivo effect is mostly due to diminished neutrophil infiltration of the liver as unmutated mice with a subchronic copper deficiency release even more NETs than their controls during endotoxemia, whereas in Wilson disease mice, excess copper directly diminishes the capacity to release NETs, and this was further confirmed by ex vivo studies on isolated neutrophils co-cultured with exogenous copper and a copper-chelating agent. Taken together, the study extends our understanding on how microenvironmental factors affect NET release by showing that copper is not a prerequisite for NET release but its excess affects the trap casting by neutrophils.

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Association study of gut flora in Wilson's disease through high-throughput sequencing

Cited by 23 publications

References 26 publications

Changes in the Gut Microbiota of Children with Autism Spectrum Disorder

Changes in the Gut Microbiota of Children with Autism Spectrum Disorder

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

Reduced Neutrophil Extracellular Trap (NET) Formation During Systemic Inflammation in Mice With Menkes Disease and Wilson Disease: Copper Requirement for NET Release

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