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The basic process of DNA methylation. S-adenosylmethionine (SAM) is used as the methyl (CH3) donor by the enzyme DNA methyltransferase (DNMT) to transfer a methyl group to cytosine rings of the DNA strands. TET proteins are dioxygenase enzymes that hydroxylate 5-methylcytosine residues to form 5-hydroxymethylcytosine (5hmC). They use a metabolite intermediate, α-ketoglutarate (α-KG), and molecular oxygen as enzyme cofactors for this reaction
Source publication
Epigenetic modulation of gene activity occurs in response to non-genetic factors such as body weight status, physical activity, dietary factors, and environmental toxins. In addition, each of these factors is thought to affect and be affected by the gut microbiome. A primary mechanism that links these various factors together in mediating control o...
Citations
... Since these factors can interact with the individual epigenetic profile and thus distort the disease-associated results, it is important to correct for them through statistical analyses. There is evidence that the composition of food can influence the individual epigenetic profile [104][105][106][107]. Longitudinal studies as well as expanded group sizes are necessary to overcome these problems. ...
Anorexia nervosa (AN) is a complex metabolic and psychological disorder that is influenced by both heritable genetic components and environmental factors. Exposure to various environmental influences can lead to epigenetically induced changes in gene expression. Epigenetic research in AN is still in its infancy, and studies to date are limited in determining clear, valid links to disease onset and progression are limited. Therefore, the aim of this systematic review was to compile and critically evaluate the available results of epigenetic studies specifically in AN and to provide recommendations for future studies. In accordance with the PRISMA guidelines, a systematic literature search was performed in three different databases (PubMed, Embase, and Web of Science) through May 2023. Twenty-three original papers or conference abstracts on epigenetic studies in AN were collected. Epigenome-wide association studies (EWASs), which analyze DNA methylation across the genome in patients with AN and identify potential disease-relevant changes in promoter/regulatory regions of genes, are the most promising for future research. To date, five EWASs on AN have been published, suggesting a potential reversibility of malnutrition-induced epigenetic changes once patients recover. Hence, determining differential DNA methylation levels could serve as a biomarker for disease status or early diagnosis and might be involved in disease progression or chronification. For future research, EWASs with a larger sample size, longitudinal study design and uniform methods should be performed to contribute to the understanding of the pathophysiology of AN, the development of individual interventions and a better prognosis for affected patients.
... This systematic review synthesized evidence from 20 studies investigating the relationship between epigenetics, microbiota, and breast cancer. The analysis of the main A huge amount of relevant data regarding the role of epigenetic modulations in the induction of diseases, the role of the microbiome, and the exact mechanisms of interaction among them in disease pathogenesis have been reported in the last decade [28]. Concerning epigenetics, some authors have highlighted the link between epigenetic modifications and breast cancer. ...
... Furthermore, the reversible nature of epigenetic modulations, in contrast to genome mutations, and the ease of manipulation of our microbiome (e.g., by changing diet and stress, among other factors) open the door to the development of safe and effective therapeutic approaches for diseases as serious and widespread as breast cancer. Manipulation of both the microbiome and diet could lead to the development of new therapies that act through epigenetic pathways and add to our tools against cancer [28]. ...
Breast cancer is the most frequently diagnosed cancer in women worldwide. According to recent studies, alterations in the microbiota and epigenetic modulations are risk factors for this disease. This systematic review aims to determine the possible associations between the intestinal and mammary microbial populations, epigenetic modifications, and breast cancer. To achieve this objective, we conducted a literature search in the PubMed, Web of Science, and Science Direct databases following the PRISMA guidelines. Although no results are yet available in humans, studies in mice suggest a protective effect of maternal dietary interventions with bioactive compounds on the development of breast tumors in offspring. These dietary interventions also modified the gut microbiota, increasing the relative abundance of short-chain fatty acid-producing taxa and preventing mammary carcinogenesis. In addition, short-chain fatty acids produced by the microbiota act as epigenetic modulators. Furthermore, some authors indicate that stress alters the gut microbiota, promoting breast tumor growth through epigenetic and gene expression changes in the breast tumor microenvironment. Taken together, these findings show the ability of epigenetic modifications and alterations of the microbiota associated with environmental factors to modulate the development, aggressiveness, and progression of breast cancer.
... The eukaryotic genome is organized into a highly compressed nucleo-protein structure known as chromatin, where DNA wraps around histone proteins and folds to form higher-order structures [128]. Different types of post-translational modifications of histones are acetylation, methylation, phosphorylation, SUMOylation, poly-ADP ribosylation, biotinylation, ubiquitination, citrullination, and proline isomerization, and these modifications can influence gene expression [129,130]. Acetylation occurs in the Lys residue of histone tails. It minimizes the positive charge of histone, reducing the interaction between histone and DNA; as a consequence, it opens the regulatory regions of genes so different TFs can bind and promote transcription. ...
Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks the colon, leading to ulcer development, loss of colon function, and bloody diarrhea. The human gut ecosystem consists of almost 2000 different species of bacteria, forming a bioreactor fueled by dietary micronutrients to produce bioreactive compounds, which are absorbed by our body and signal to distant organs. Studies have shown that the Western diet, with fewer short-chain fatty acids (SCFAs), can alter the gut microbiome composition and cause the host’s epigenetic reprogramming. Additionally, overproduction of H2S from the gut microbiome due to changes in diet patterns can further activate pro-inflammatory signaling pathways in UC. This review discusses how the Western diet affects the microbiome’s function and alters the host’s physiological homeostasis and susceptibility to UC. This article also covers the epidemiology, prognosis, pathophysiology, and current treatment strategies for UC, and how they are linked to colorectal cancer.
... Previous research indicated an association between dietary www.nature.com/scientificreports/ phytochemicals and SCFA-producing gut microbiota 37 . Here, we also investigated the changes in gut microbial composition of C3 mice due to single or combinatorial dietary supplements. ...
Estrogen receptor-negative [ER(−)] mammary cancer is the most aggressive type of breast cancer (BC) with higher rate of metastasis and recurrence. In recent years, dietary prevention of BC with epigenetically active phytochemicals has received increased attention due to its feasibility, effectiveness, and ease of implementation. In this regard, combinatorial phytochemical intervention enables more efficacious BC inhibition by simultaneously targeting multiple tumorigenic pathways. We, therefore, focused on investigation of the effect of sulforaphane (SFN)-rich broccoli sprouts (BSp) and withaferin A (WA)-rich Ashwagandha (Ash) combination on BC prevention in estrogen receptor-negative [ER(−)] mammary cancer using transgenic mice. Our results indicated that combinatorial BSp + Ash treatment significantly reduced tumor incidence and tumor growth (~ 75%) as well as delayed (~ 21%) tumor latency when compared to the control treatment and combinatorial BSp + Ash treatment was statistically more effective in suppressing BC compared to single BSp or Ash intervention. At the molecular level, the BSp and Ash combination upregulated tumor suppressors (p53, p57) along with apoptosis associated proteins (BAX, PUMA) and BAX:BCL-2 ratio. Furthermore, our result indicated an expressional decline of epigenetic machinery HDAC1 and DNMT3A in mammary tumor tissue because of combinatorial treatment. Interestingly, we have reported multiple synergistic interactions between BSp and Ash that have impacted both tumor phenotype and molecular expression due to combinatorial BSp and Ash treatment. Our RNA-seq analysis results also demonstrated a transcriptome-wide expressional reshuffling of genes associated with multiple cell-signaling pathways, transcription factor activity and epigenetic regulations due to combined BSp and Ash administration. In addition, we discovered an alteration of gut microbial composition change because of combinatorial treatment. Overall, combinatorial BSp and Ash supplementation can prevent ER(−) BC through enhanced tumor suppression, apoptosis induction and transcriptome-wide reshuffling of gene expression possibly influencing multiple cell signaling pathways, epigenetic regulation and reshaping gut microbiota.
... From Figure 6, we can find that the co-cited references are divided into four clusters, corresponding to the four colors in the visualization diagram. The red cluster mainly shows the epigenetic regulation of host metabolism by intestinal microbes, including the epigenetic regulation of host obesity by gut microbiota (10), the interaction between diet and intestinal microbes mediates the epigenetic inheritance of host tissues or diseases (11,12), and the epigenetic regulation between gut microbiota and host metabolism (13,14). The literature on green clusters mainly introduces the research on the types and functions of gut microbiota and gene sequencing (15)(16)(17). ...
Background
Gut microbiota is an important factor affecting host health. With the further study of the mechanism of gut microbiota, significant progress has been made in the study of the link between gut microbiota and epigenetics. This study visualizes the body of knowledge and research priorities between the gut microbiota and epigenetics through bibliometrics.
Methods
Publications related to gut microbiota and epigenetics were searched in the Web of Science Core Collection (WoSCC) database. Vosviewer 1.6.17 and CiteSpace 6.1.R2 were used for bibliometric analysis.
Results
WoSCC includes 460 articles from 71 countries. The number of publications on gut microbiota and epigenetics has increased each year since 2011. The USA, PEOPLES R CHINA, and ITALY are at the center of this field of research. The University of California System, Harvard University, and the University of London are the main research institutions. Li, X, Yu, Q, Zhang, S X are the top authors in this research field. We found that current research hotspots and frontiers include short-chain fatty acids (SCFA) play an important role in gut microbiota and epigenetic mechanisms, gut microbiota and epigenetics play an important role in host obesity, diet, and metabolism. Gut microbiota and epigenetics are closely related to colorectal cancer, breast cancer, and inflammatory bowel disease. At the same time, we found that gut microbiota regulates epigenetics through the gut-brain axis and has an impact on psychiatric diseases. Therefore, probiotics can regulate gut microbiota, improve lifestyle, and reduce the occurrence and development of diseases.
Conclusion
This is the first comprehensive and in-depth bibliometric study of trends and developments in the field of gut microbiota and epigenetics research. This study helps to guide the direction of research scholars in their current field of study.
... Recent research has highlighted their importance for learning and memory, with cuts in SCFAs associated with inflammation in Multiple Sclerosis patients and compromised neuronal function in various neurodegenerative diseases [199,200]. Furthermore, SCFAs appear to have neuroprotective roles, affecting the brain indirectly or directly by acting as ligands for GPCRs or as epigenetic modulators of HDAC to control transcriptional changes that affect neuronal functions [201][202][203][204][205]. The diminished concentration of SCFAs is suggested to be a critical factor in disrupting gut-brain balance, but the role of SCFAs in this context is under active investigation. ...
The gastrointestinal tract is home to trillions of diverse microorganisms collectively known as the gut microbiota, which play a pivotal role in breaking down undigested foods, such as dietary fibers. Through the fermentation of these food components, short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate are produced, offering numerous health benefits to the host. The production and absorption of these SCFAs occur through various mechanisms within the human intestine, contingent upon the types of dietary fibers reaching the gut and the specific microorganisms engaged in fermentation. Medical literature extensively documents the supplementation of SCFAs, particularly butyrate, in the treatment of gastrointestinal, metabolic, cardiovascular, and gut-brain-related disorders. This review seeks to provide an overview of the dynamics involved in the production and absorption of acetate, propionate, and butyrate within the human gut. Additionally, it will focus on the pivotal roles these SCFAs play in promoting gastrointestinal and metabolic health, as well as their current therapeutic implications.
... Recent research has highlighted their importance for learning and memory, with cuts in SCFAs associated with inflammation in Multiple Sclerosis patients and compromised neuronal function in various neurodegenerative diseases [214,215]. Furthermore, SCFAs appear to have neuroprotective roles, affecting the brain indirectly or directly by acting as ligands for GPCRs or as epigenetic modulators of HDAC to control transcriptional changes that affect neuronal functions [216][217][218][219][220]. The diminished concentration of SCFAs is suggested to be a critical factor in disrupting gut-brain balance, but the role of SCFA in this context is under active investigation. ...
The gastrointestinal tract is colonized by trillions of different microorganisms, named the gut microbiota, which is key to degrade undigested food such as dietary fibers. The fermentation of these food components leads to the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which exploit several beneficial roles for the host’s health. Their production and absorption happen in different ways in the human intestine and depend on the type of dietary fiber reaching the gut and the microorganisms involved in the fermentation. The supplementation of SCFAs, mostly butyrate, in treating gastrointestinal, metabolic, cardiovascular, and gut-brain-related diseases has been reported in the medical literature. This review aims to give an overview of the production and absorption dynamics of acetate, propionate, and butyrate in the human gut, with a final focus on the role played by these SCFAs on gastrointestinal and metabolic health and the present therapeutic implications.
... The metabolic pathways depending on microbes probably have a major role in promoting aggressive tumor expansion in breast cancers linked to food. Nonetheless, research has shown that different eating habits might increase the proliferation of eubiotic microorganisms, which is beneficial for cancer treatment (Paul et al. 2015). Numerous investigators have aimed to establish a correlation among microbiological species, particularly dietary regimens such as the Mediterranean diet, and breast cancer. ...
According to recent research, bacterial imbalance in the gut microbiota and breast tissue may be linked to breast cancer. It has been discovered that alterations in the makeup and function of different types of bacteria found in the breast and gut may contribute to growth and advancement of breast cancer in several ways. The main role of gut microbiota is to control the metabolism of steroid hormones, such as estrogen, which are important in raising the risk of breast cancer, especially in women going through menopause. On the other hand, because the microbiota can influence mucosal and systemic immune responses, they are linked to the mutual interactions between cancer cells and their local environment in the breast and the gut. In this regard, the current review thoroughly explains the mode of action of probiotics and microbiota to eradicate the malignancy. Furthermore, immunomodulation by microbiota and probiotics is described with pathways of their activity.
... While investigation of epigenetic-microbial interactions is of growing interest in cancer, obesity, and neurodevelopmental research [28,61,62], this is an uncharted question in the field of developmental programming. Bacterial populations in a host can affect epigenetic regulation and correlate with clinical outcomes: gut microbial dysbiosis leads to inflammation, decrease in SCFA, and increased risk of inflammatory bowel disease IBD) [63]. ...
Understanding how maternal diet affects in utero neonatal gut microbiota and epigenetic regulation may provide insight into disease origins and long-term health. The impact of Mediterranean diet pattern adherence (MDA) on fetal gut microbiome and epigenetic regulation was assessed in 33 pregnant women. Participants completed a validated food frequency questionnaire in each trimester of pregnancy; the alternate Mediterranean diet (aMED) score was applied. Umbilical cord blood, placental tissue, and neonatal meconium were collected from offspring. DNA methylation patterns were probed using the Illumnia EPICarray Methylation Chip in parturients with high versus low MDA. Meconium microbial abundance in the first 24 h after birth was identified using 16s rRNA sequencing and compared among neonates born to mothers with high and low aMED scores. Twenty-one mothers were classified as low MDA and 12 as high MDA. Pasteurellaceae and Bacteroidaceae trended towards greater abundance in the high-MDA group, as well as other short-chain fatty acid-producing species. Several differentially methylated regions varied between groups and overlapped gene regions including NCK2, SNED1, MTERF4, TNXB, HLA-DPB, BAG6, and LMO3. We identified a beneficial effect of adherence to a Mediterranean diet on fetal in utero development. This highlights the importance of dietary counseling for mothers and can be used as a guide for future studies of meconium and immuno-epigenetic modulation.
... The molecular mechanisms of microbiota-modulated neuroinflammation, acting both locally and systemically, have begun to be elucidated. For example, gut microbiota metabolites have been shown to inhibit host histone deacetylases (HDACs), which, as key modifiers of histones, control the assembly of transcriptional complexes, facilitating the active state of the host genome [5,6]. Persistent changes in the intestinal microbiota can lead to increased production of proinflammatory cytokines, causing increased intestinal permeability [7]. ...
The gut-brain axis is a critical communication system influencing the interactions between the gastrointestinal tract (GI) and the central nervous system (CNS). The gut microbiota plays a significant role in this axis, affecting the development and function of the nervous system. Stress-induced psychopathologies, such as depression and anxiety, have been linked to the gut microbiota, but underlying mechanisms and genetic susceptibility remain unclear. In this study, we examined stress-induced changes in the gut microbiome composition in two rat strains with different levels of nervous system excitability: high threshold (HT strain) and low threshold (LT strain). Rats were exposed to long-term emotional and painful stress using the Hecht protocol, and fecal samples were collected at multiple time points before and after stress exposure. Using 16S rRNA amplicon sequencing, we assessed the qualitative and quantitative changes in the gut microbiota. Our results revealed distinct microbial diversity between the two rat strains, with the HT strain displaying higher diversity compared to the LT strain. Notably, under prolonged stress, the HT strain showed an increase in relative abundance of microorganisms from the genera Faecalibacterium and Prevotella in fecal samples. Additionally, both strains exhibited a decrease in Lactobacillus abundance following stress exposure. Our findings provide valuable insights into the impact of hereditary nervous system excitability on the gut microbiome composition under stress conditions. Understanding the gut-brain interactions in response to stress may open new avenues for comprehending stress-related psychopathologies and developing potential therapeutic interventions targeted at the gut microbiota. However, further research is needed to elucidate the exact mechanisms underlying these changes and their implications for stress-induced disorders. Overall, this study contributes to the growing body of knowledge on the gut-brain axis and its significance in stress-related neurobiology.
