Colonization of the Caenorhabditis elegans gut with human enteric bacterial pathogens leads to proteostasis disruption that is rescued by butyrate

Walker, Alyssa C; Bhargava, Rohan; Vaziriyan-Sani, Alfonso S.; Pourciau, Christine; Donahue, Emily T.; Dove, Autumn S.; Gebhardt, Michael; Ellward, Garrett L.; Romeo, Tony; Czyż, Daniel M.

doi:10.1371/journal.ppat.1009510

Cited by 43 publications

(51 citation statements)

References 89 publications

(127 reference statements)

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“…Lipid analysis in fat-1-de cient nematodes revealed a signi cant reduction in heptadecaenoic acid, while other major FAs were unaffected 41 . Caenorhabditis elegans intestinal colonization causes protein homeostasis disruption, which can be improved by butyrate 42 . Two peptides, ACAN1 and NAK1, derived from the nematode phylum, have immunomodulatory functions and can inhibit the proliferation of CD4+ T cells and the production of IL-2 and TNF 43 .…”

Section: Discussionmentioning

confidence: 99%

Multi-omics Reveal the Enabling Factors of Aplastic Anaemia

Zhao

Wang

Liu

et al. 2022

Preprint

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Background: Aplastic anemia is a kind of anemia caused by bone marrow failure due to autoimmune abnormalities. Numerous studies have shown that autoimmunity is regulated by intestinal microflora, and that most intestinal microflora regulates immunity through short chain fatty acids. At the same time, almost all patients with aplastic anemia will have bone marrow adipose tissue, and the process of bone marrow adipose tissue is regulated by medium and long chain fatty acids. Our previous studies have found that the intestinal flora of aplastic anemia patients is different from that of normal people. Therefore, this study aims to conduct a comprehensive detection of the intestinal flora and fatty acid metabolism in patients with aplastic anemia and to study their correlation.Methods: Fatty acid compositions in the peripheral plasma and bone marrow supernatants of 12 newly diagnosed aplastic anaemia patients and 10 normal controls were comprehensively analysed by CG-MS. Gene sequencing of faecal samples from both groups was also performed with macrogene sequencing technology.Results: Based on the metagenomic sequencing technology, we analyzed the difference of intestinal flora between group AA and group NC. We found that the main difference between the two groups existed in the bacterial community, and the abundance of most microbial species showed a downward trend. Based on the CG-MS lipid detection technique, we found that there were differences in lipid metabolism between the AA group and the NC group, whether short chain fatty acids or medium and long chain fatty acids. 8. The most attractive findings are interrelationships between the Citrobacter spp 、stearic acid (c18:0), isobutyric acid, and lysine degradation and betaine biosynthesis pathway and the interrelationship between catenibacterium_mitsuokai species at Catenibacterium, cis-7,10,13,16-docosatetraenoic acid (c22:4), ubiquinone and other terpenoid quinones pathway.We also found the intercorrelation between the abundance of Enhydrobacter genus and Enhydrobacter_aerosaccus species, cis-13,16-docosadienoic acid in peripheral plasma, cis-7,10,13,16-docosatetraenoic acid in bone marrow supernatant, tyrosine and tryptophan biosynthesis pathways.Conclusions: Our results show that Citrobacter infection may be a driving factor for aplastic anaemia, identifying a potential role for stearic acid in the immunopathogenesis of aplastic anaemia. Our study also demonstrates the potential role of 22-carbon long-chain polyunsaturated fatty acids, which may not only be involved in the metabolism of fibroblasts in bone marrow but also influence the formation of the bone marrow microenvironment, in aplastic anaemia.

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Section: Discussionmentioning

confidence: 99%

Multi-omics Reveal the Enabling Factors of Aplastic Anaemia

Zhao

Wang

Liu

et al. 2022

Preprint

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“…In our opinion, and after the extensive research work carried out to develop this work, future lines of research should focus on three main axes. First, new AChEI that delay the evolution of the disease, more efficient treatments are in progress based on super-AChEI designed under the “multitarget small molecule” umbrella [ 62 ]; secondly, studying epigenetics and designing drugs that are capable of modifying the human genome that cause AD [ 63 , 64 ] and, thirdly, the study of the human microbiota and how it influences the development of pathologies that trigger AD [ 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Acetylcholinesterase Inhibitors on Cognitive Function in Alzheimer’s Disease. Review of Reviews

et al. 2021

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Alzheimer’s disease (AD) is the most common form of dementia over the age of 65. It is estimated that 115.4 million people will be affected by AD by 2050. Acetylcholinesterase inhibitors (AChEI) are the only available and approved treatment for AD. The aim of the present study was to analyse the evidence on the efficacy of the AChEI in the treatment of cognitive symptoms of Alzheimer’s disease. For that purpose, a review of review of the systematic reviews (SRs) on this topic was carried out by Web of Science, PubMed, and The Cochrane Library, among others, were searched until 24 September 2021. Thirteen of the 1773 articles evaluated the efficacy of AChEI on cognitive function and/or general condition and/or behavioural disturbances of patients with mild to moderate AD. Methodological quality and risk of bias were rated using the ROBIS scale. The quality of the identified studies was high for nine of them, unclear for two, and finally only in two of the 13 studies did we detect low quality. Overall, AChEI showed very low efficacy in improving cognition in patients with mild to moderate AD. Better results were obtained in improving global state, with donepezil being the most effective treatment. No improvements in behavioural disturbances were found. Few high-quality reviews provide clear evidence of the effects of AChEI on cognition, global change, behaviour, and mortality. The data suggest that AChEI stabilize or slow cognitive deterioration, improving global status. In addition, data indicate that the use of AChEI decreases mortality in patients with mild to moderate AD. However, there is no evidence that they improve patient behaviour. Donepezil is the best therapeutic alternative at a dose of 10 mg/day.

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“…To study the link between gut microbes and protein aggregation, Caenorhabditis elegans is used as a model organism. A study demonstrates that colonization of C. elegans gut with bacterial pathogens disrupted the intestines, muscles, and neurons and increased protein aggregation (Lau et al, 2021;Walker et al, 2021). Further investigation revealed that co-colonization with butyrogenic bacteria inhibited the aggregation of protein in C. elegans indicating that enteric bacteria play a role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (Lau et al, 2021;Walker et al, 2021).…”

Section: Microbiome Role In Alzheimer and Dementiamentioning

confidence: 99%

Recent Advances in Understanding the Structure and Function of the Human Microbiome

2022

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Trillions of microbes live within our bodies in a deep symbiotic relationship. Microbial populations vary across body sites, driven by differences in the environment, immunological factors, and interactions between microbial species. Major advances in genome sequencing enable a better understanding of microbiome composition. However, most of the microbial taxa and species of the human microbiome are still unknown. Without revealing the identity of these microbes as a first step, we cannot appreciate their role in human health and diseases. A shift in the microbial balance, termed dysbiosis, is linked to a broad range of diseases from simple colitis and indigestion to cancer and dementia. The last decade has witnessed an explosion in microbiome research that led to a better understanding of the microbiome structure and function. This understanding leads to potential opportunities to develop next-generation microbiome-based drugs and diagnostic biomarkers. However, our understanding is limited given the highly personalized nature of the microbiome and its complex and multidirectional interactions with the host. In this review, we discuss: (1) our current knowledge of microbiome structure and factors that shape the microbial composition, (2) recent associations between microbiome dysbiosis and diseases, and (3) opportunities of new microbiome-based therapeutics. We analyze common themes, promises, gaps, and challenges of the microbiome research.

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Colonization of the Caenorhabditis elegans gut with human enteric bacterial pathogens leads to proteostasis disruption that is rescued by butyrate

Cited by 43 publications

References 89 publications

Multi-omics Reveal the Enabling Factors of Aplastic Anaemia

Multi-omics Reveal the Enabling Factors of Aplastic Anaemia

Efficacy of Acetylcholinesterase Inhibitors on Cognitive Function in Alzheimer’s Disease. Review of Reviews

Recent Advances in Understanding the Structure and Function of the Human Microbiome

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