Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome

Vossen, Eduard W. J. van der; Bastos, D.; Stols-Gonçalves, Daniela; Goffau, Marcus C. de; Davids, Mark; Pereira, João; Yim, Andrew Y. Li; Henneman, Peter; Netea, Mihai G.; Vos, Willem M. de; Jonge, Wouter J. de; Groen, Albert K.; Nieuwdorp, Max; Levin, Evgeni

doi:10.1080/19490976.2021.1993513

Cited by 33 publications

(24 citation statements)

References 62 publications

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“…Next, we investigated whether DNA methylation could be of use for distinguishing patients with PSC-UC from patients with UC without PSC. To this end, we performed a classification analysis using repeated cross-validation with gradient boosting, where we sought to capitalize on potential non-linear relationships between the CpG loci of interest and the presence of PSC-UC ( 34 ). Altogether, the classification analysis yielded a predictive model with an area under the receiver-operator characteristic curve (AUROC) of 0.80.…”

Section: Resultsmentioning

confidence: 99%

“…Gradient boosting analysis was used to classify patients with PSC-UC from patients with UC. To identify the CpGs that contributed the most to the predictive performance, covered information disentanglement (CID) was implemented ( 31 – 34 ). In short, data was split up in a train (2/3) and test (1/3) set, whereupon the classifier was trained through repeated cross-validation on the training set.…”

Section: Methodsmentioning

confidence: 99%

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Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis

et al. 2022

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BackgroundPrimary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone.MethodsThe peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array. Differentially methylated CpG position (DMP) and region (DMR) analyses were performed alongside gradient boosting classification analyses to discern PSC-UC from UC patients. As observed differences in the DNA methylome could be the result of differences in cellular populations, we additionally employed mass cytometry (CyTOF) to characterize the immune cell compositions.ResultsGenome wide methylation analysis did not reveal large differences between PSC-UC and UC patients nor HCs. Nonetheless, using gradient boosting we were capable of discerning PSC-UC from UC with an area under the receiver operator curve (AUROC) of 0.80. Four CpG sites annotated to the NINJ2 gene were found to strongly contribute to the predictive performance. While CyTOF analyses corroborated the largely similar blood cell composition among patients with PSC-UC, UC and HC, a higher abundance of myeloid cells was observed in UC compared to PSC-UC patients.ConclusionDNA methylation enables discerning PSC-UC from UC patients, with a potential for biomarker development.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis

et al. 2022

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“…Mounting evidence has shown a strong association between gut microbiota and hepatic metabolic disorders, including obesity, diabetes, and NAFLD [ 3 , 4 , 30 , 31 ]. Therefore, strategies to alter the gut microbiome have been used for the treatment of metabolic disorders in clinical studies [ 32 , 33 , 34 ]. It is vital to understand the mechanism of gut microbiota in regulating host hepatic metabolism, especially lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice

Han

Wang

Zhong

et al. 2022

IJMS

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Dysregulated lipid metabolism is a key pathology in metabolic diseases and the liver is a critical organ for lipid metabolism. The gut microbiota has been shown to regulate hepatic lipid metabolism in the host. However, the underlying mechanism by which the gut microbiota influences hepatic lipid metabolism has not been elucidated. Here, a gut microbiota depletion mouse model was constructed with an antibiotics cocktail (Abx) to study the mechanism through which intestinal microbiota regulates hepatic lipid metabolism in high-fat diet (HFD)-fed mice. Our results showed that the Abx treatment effectively eradicated the gut microbiota in these mice. Microbiota depletion reduced the body weight and fat deposition both in white adipose tissue and liver. In addition, microbiota depletion reduced serum levels of glucose, total cholesterol (TC), low-density lipoproteins (LDL), insulin, and leptin in HFD-fed mice. Importantly, the depletion of gut microbiota in HFD-fed mice inhibited excessive hepatic lipid accumulation. Mechanistically, RNA-seq results revealed that gut microbiota depletion changed the expression of hepatic genes involved in cholesterol and fatty acid metabolism, such as Cd36, Mogat1, Cyp39a1, Abcc3, and Gpat3. Moreover, gut microbiota depletion reduced the abundance of bacteria associated with abnormal metabolism and inflammation, including Lachnospiraceae, Coriobacteriaceae_UCG-002, Enterorhabdus, Faecalibaculum, and Desulfovibrio. Correlation analysis showed that there was strong association between the altered gut microbiota abundance and the serum cholesterol level. This study indicates that gut microbiota ameliorates HFD-induced hepatic lipid metabolic dysfunction, which might be associated with genes participating in cholesterol and fatty acid metabolism in the liver.

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“…Numerous investigations have evaluated the hypothesis of changing the gut microbio ta as a promising treatment for metabolic diseases like obesity and other metabolic syndromes ( 13 ). Recently, the efficacy of FMT has been observed in changing not only the gut microbiome composition but also the host metabolome and epigenome of immune cells ( 14 ). Several case reports and animal models have also revealed the probable therapeutic effects of FMT in patients with severe multiple sclerosis ( 15 ), autism ( 16 ), multidrug-resistant (MDR) infections ( 17 ), and multiple organ dysfunction in critical patients ( 18 ).…”

Section: Fmt For Extraintestinal Disordersmentioning

confidence: 99%

Orchestrating the fecal microbiota transplantation: Current technological advancements and potential biomedical application

Nigam

Panwar

Singh

2022

Front. Med. Technol.

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Fecal microbiota transplantation (FMT) has been proved to be an effective treatment for gastrointestinal disorders caused due to microbial disbalance. Nowadays, this approach is being used to treat extragastrointestinal conditions like metabolic and neurological disorders, which are considered to have their provenance in microbial dysbiosis in the intestine. Even though case studies and clinical trials have demonstrated the potential of FMT in treating a variety of ailments, safety and ethical concerns must be answered before the technique is widely used to the community's overall benefit. From this perspective, it is not unexpected that techniques for altering gut microbiota may represent a form of medication whose potential has not yet been thoroughly addressed. This review intends to gather data on recent developments in FMT and its safety, constraints, and ethical considerations.

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Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome

Cited by 33 publications

References 62 publications

Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis

Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis

Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice

Orchestrating the fecal microbiota transplantation: Current technological advancements and potential biomedical application

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