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Ntiri ES, Chun Nin Wong A. Microbial metabolites as engines of behavioral variation across animals. Gut Microbes 2025; 17:2501191. [PMID: 40357979 PMCID: PMC12077453 DOI: 10.1080/19490976.2025.2501191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 04/07/2025] [Accepted: 04/28/2025] [Indexed: 05/15/2025] Open
Abstract
The microbiome, especially that present in the gut, has emerged as a key modulator of animal behavior. However, the extent of its influence across species and behavioral repertoires, as well as the underlying mechanisms, remains poorly understood. Increasing evidence suggests that microbial metabolites play an important role in driving behavioral variation. In this review, we synthesize findings from vertebrates to invertebrates, spanning both model and non-model organisms, to define key groups of microbial-derived metabolites involved in modulating seven distinct behaviors: nutrition, olfaction, circadian rhythms, reproduction, locomotion, aggression, and social interactions. We discuss how these microbial metabolites interact with host chemosensory systems, neurotransmitter signaling, and epigenetic modifications to shape behavior. Additionally, we highlight critical gaps in mechanistic understanding, including the need to map additional host receptors and signaling pathways, as well as the untapped potential of microbial biosynthetic gene clusters as sources for novel bioactive compounds. Advancing these areas will enhance understanding of the microbiome's role in behavioral modulation and open new avenues for microbiome-based interventions for behavioral disorders.
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Affiliation(s)
- Eric Siaw Ntiri
- Entomology and Nematology Department, University of Florida, Gainesville, FL, USA
| | - Adam Chun Nin Wong
- Entomology and Nematology Department, University of Florida, Gainesville, FL, USA
- Genetics Institute, University of Florida, Gainesville, FL, USA
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2
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Nisar MF, Yan T, Cai Y, Wan C. Immuno-oncological Challenges and Chemoresistance in Veterinary Medicine: Probiotics as a New Strategic Tool. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10468-8. [PMID: 39954194 DOI: 10.1007/s12602-025-10468-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2025] [Indexed: 02/17/2025]
Abstract
Cancer has the highest death rates due to increased immuno-oncological (IO) challenges and chemoresistance caused by gut dysbiosis, whereas administration of probiotics may reverse these responses against anticancer therapies. Recently, immunotherapeutics have extensively been focused for significant advancements in pharmacological drug discovery and clinical outcomes. Mammals have intestinal epithelial cells, mucosal immune cells, and indigenous gut microbiota which may reshape immunotherapeutics efficacy. These include use of T-cell immune checkpoint inhibitors (ICPI), genetically engineered T-cells, tumor vaccines, monoclonal antibodies (mAbs), and anti-B- and T-cell antibodies. Immunotherapeutics for cancer treatment became popular in both veterinary and human health care systems due to their strong inhibitory actions against PD-1 and CTLA-4 to check tumorigenesis. IO issues in animals also need special attention, where caninized mAbs targeting CD-20 and CD-52 have been clinically used in treating canine B-cell and T-cell lymphomas, respectively. Probiotics appeared as strong immunotherapeutics that might be shaping the epigenetics of the organisms specifically in animal breeding practices for desired features, but limited literature regarding the immunomodulatory effects in humans and animals is available. In addition, considering the important role of probiotics in humans and veterinary medicine, a new perspective on the probiotic-mediated modulation of ncRNAs (miRNAs, lncRNAs, circRNAs) is also highlighted and would be a new therapeutic tool. This review provides insight into the cellular processes and pharmacological activities for treating veterinary infectious diseases and covers small drug molecules as ncRNA-modulators in veterinary medicine.
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Affiliation(s)
- Muhammad Farrukh Nisar
- Ministry of Education and Jiangxi Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Jiangxi Agricultural University, Nanchang, 330045, China
- Jiangxi Key Laboratory for Post-harvest Technology and Nondestructive Testing of Fruits & Vegetables, College of Agronomy, Jiangxi Agricultural University, Nanchang, 330045, China
- Department of Physiology and Biochemistry, Cholistan University of Veterinary and Animal Sciences (CUVAS), Bahawalpur, Pakistan
| | - Tingdong Yan
- School of Pharmacy, Nantong University, Nantong, 226001, China.
| | - Yi Cai
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China
| | - Chunpeng Wan
- Jiangxi Key Laboratory for Post-harvest Technology and Nondestructive Testing of Fruits & Vegetables, College of Agronomy, Jiangxi Agricultural University, Nanchang, 330045, China.
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Pepke ML, Hansen SB, Limborg MT. Unraveling host regulation of gut microbiota through the epigenome-microbiome axis. Trends Microbiol 2024; 32:1229-1240. [PMID: 38839511 DOI: 10.1016/j.tim.2024.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 05/13/2024] [Accepted: 05/15/2024] [Indexed: 06/07/2024]
Abstract
Recent studies of dynamic interactions between epigenetic modifications of a host organism and the composition or activity of its associated gut microbiota suggest an opportunity for the host to shape its microbiome through epigenetic alterations that lead to changes in gene expression and noncoding RNA activity. We use insights from microbiota-induced epigenetic changes to review the potential of the host to epigenetically regulate its gut microbiome, from which a bidirectional 'epigenome-microbiome axis' emerges. This axis embeds environmentally induced variation, which may influence the adaptive evolution of host-microbe interactions. We furthermore present our perspective on how the epigenome-microbiome axis can be understood and investigated within a holo-omic framework with potential applications in the applied health and food sciences.
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Affiliation(s)
- Michael L Pepke
- Center for Evolutionary Hologenomics, Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen, Øster Farimagsgade 5, DK-1353 Copenhagen, Denmark.
| | - Søren B Hansen
- Center for Evolutionary Hologenomics, Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen, Øster Farimagsgade 5, DK-1353 Copenhagen, Denmark
| | - Morten T Limborg
- Center for Evolutionary Hologenomics, Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen, Øster Farimagsgade 5, DK-1353 Copenhagen, Denmark.
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4
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Seo H, Capece SH, Hill JD, Otten JK, Papoutsakis ET. Butyrate as a growth factor of Clostridium acetobutylicum. Metab Eng 2024; 86:194-207. [PMID: 39413987 DOI: 10.1016/j.ymben.2024.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 09/01/2024] [Accepted: 10/13/2024] [Indexed: 10/18/2024]
Abstract
The butyrate biosynthetic pathway not only contributes to electron management and energy generation in butyrate forming bacteria, but also confers evolutionary advantages to the host by inhibiting the growth of surrounding butyrate-sensitive microbes. While high butyrate levels induce toxic stress, effects of non-toxic levels on cell growth, health, metabolism, and sporulation remain unclear. Here, we show that butyrate stimulates cellular processes of Clostridium acetobutylicum, a model butyrate forming Firmicute. First, we deleted the 3-hydroxybutyryl-CoA dehydrogenase gene (hbd) from the C. acetobutylicum chromosome to eliminate the butyrate synthetic pathway and thus butyrate formation. A xylose inducible Cas9 cassette was chromosomally integrated and utilized for the one-step markerless gene deletions. Non-toxic butyrate levels significantly affected growth, health, and sporulation of C. acetobutylicum. After deleting spo0A, the gene encoding the master regulator of sporulation, Spo0A, and conducting butyrate addition experiments, we conclude that butyrate affects cellular metabolism through both Spo0A-dependent and independent mechanisms. We also deleted the hbd gene from the chromosome of the asporogenous C. acetobutylicum M5 strain lacking the pSOL1 plasmid to examine the potential involvement of pSOL1 genes on the observed butyrate effects. Addition of crotonate, the precursor of butyrate biosynthesis, to the hbd deficient M5 strain was used to probe the role of butyrate biosynthesis pathway in electron and metabolic fluxes. Finally, we found that butyrate addition can enhance the growth of the non-butyrate forming Clostridium saccharolyticum. Our data suggest that butyrate functions as a stimulator of cellular processes, like a growth factor, in C. acetobutylicum and potentially evolutionarily related Clostridium organisms.
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Affiliation(s)
- Hyeongmin Seo
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA
| | - Sofia H Capece
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA
| | - John D Hill
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA
| | - Jonathan K Otten
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA
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Tain YL, Hsu CN. Interplay between maternal nutrition and epigenetic programming on offspring hypertension. J Nutr Biochem 2024; 127:109604. [PMID: 38373508 DOI: 10.1016/j.jnutbio.2024.109604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 01/19/2024] [Accepted: 02/15/2024] [Indexed: 02/21/2024]
Abstract
Recent human and animal studies have delineated hypertension can develop in the earliest stage of life. A lack or excess of particular nutrients in the maternal diet may impact the expression of genes associated with BP, leading to an increased risk of hypertension in adulthood. Modulations in gene expression could be caused by epigenetic mechanisms through aberrant DNA methylation, histone modification, and microRNAs (miRNAs). Several molecular mechanisms for the developmental programming of hypertension, including oxidative stress, dysregulated nutrient-sensing signal, aberrant renin-angiotensin system, and dysbiotic gut microbiota have been associated with epigenetic programming. Conversely, maternal nutritional interventions such as amino acids, melatonin, polyphenols, resveratrol or short chain fatty acids may work as epigenetic modifiers to trigger protective epigenetic modifications and prevent offspring hypertension. We present a current perspective of maternal malnutrition that can cause fetal programming and the potential of epigenetic mechanisms lead to offspring hypertension. We also discuss the opportunities of dietary nutrients or nutraceuticals as epigenetic modifiers to counteract those adverse programming actions for hypertension prevention. The extent to which aberrant epigenetic changes can be reprogrammed or reversed by maternal dietary interventions in order to prevent human hypertension remains to be established. Continued research is necessary to evaluate the interaction between maternal malnutrition and epigenetic programming, as well as a greater focus on nutritional interventions for hypertension prevention towards their use in clinical translation.
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Affiliation(s)
- You-Lin Tain
- Division of Pediatric Nephrology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Pereira QC, Fortunato IM, Oliveira FDS, Alvarez MC, dos Santos TW, Ribeiro ML. Polyphenolic Compounds: Orchestrating Intestinal Microbiota Harmony during Aging. Nutrients 2024; 16:1066. [PMID: 38613099 PMCID: PMC11013902 DOI: 10.3390/nu16071066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/20/2024] [Accepted: 03/21/2024] [Indexed: 04/14/2024] Open
Abstract
In the aging process, physiological decline occurs, posing a substantial threat to the physical and mental well-being of the elderly and contributing to the onset of age-related diseases. While traditional perspectives considered the maintenance of life as influenced by a myriad of factors, including environmental, genetic, epigenetic, and lifestyle elements such as exercise and diet, the pivotal role of symbiotic microorganisms had been understated. Presently, it is acknowledged that the intestinal microbiota plays a profound role in overall health by signaling to both the central and peripheral nervous systems, as well as other distant organs. Disruption in this bidirectional communication between bacteria and the host results in dysbiosis, fostering the development of various diseases, including neurological disorders, cardiovascular diseases, and cancer. This review aims to delve into the intricate biological mechanisms underpinning dysbiosis associated with aging and the clinical ramifications of such dysregulation. Furthermore, we aspire to explore bioactive compounds endowed with functional properties capable of modulating and restoring balance in this aging-related dysbiotic process through epigenetics alterations.
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Affiliation(s)
- Quélita Cristina Pereira
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.); (T.W.d.S.)
| | - Isabela Monique Fortunato
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.); (T.W.d.S.)
| | - Fabricio de Sousa Oliveira
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.); (T.W.d.S.)
| | - Marisa Claudia Alvarez
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.); (T.W.d.S.)
- Hematology and Transfusion Medicine Center, University of Campinas/Hemocentro, UNICAMP, Rua Carlos Chagas 480, Campinas 13083-878, SP, Brazil
| | - Tanila Wood dos Santos
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.); (T.W.d.S.)
| | - Marcelo Lima Ribeiro
- Laboratory of Immunopharmacology and Molecular Biology, Sao Francisco University, Av. Sao Francisco de Assis, 218, Braganca Paulista 12916-900, SP, Brazil; (Q.C.P.); (I.M.F.); (F.d.S.O.); (M.C.A.); (T.W.d.S.)
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Auclert LZ, Chhanda MS, Derome N. Interwoven processes in fish development: microbial community succession and immune maturation. PeerJ 2024; 12:e17051. [PMID: 38560465 PMCID: PMC10981415 DOI: 10.7717/peerj.17051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 02/13/2024] [Indexed: 04/04/2024] Open
Abstract
Fishes are hosts for many microorganisms that provide them with beneficial effects on growth, immune system development, nutrition and protection against pathogens. In order to avoid spreading of infectious diseases in aquaculture, prevention includes vaccinations and routine disinfection of eggs and equipment, while curative treatments consist in the administration of antibiotics. Vaccination processes can stress the fish and require substantial farmer's investment. Additionally, disinfection and antibiotics are not specific, and while they may be effective in the short term, they have major drawbacks in the long term. Indeed, they eliminate beneficial bacteria which are useful for the host and promote the raising of antibiotic resistance in beneficial, commensal but also in pathogenic bacterial strains. Numerous publications highlight the importance that plays the diversified microbial community colonizing fish (i.e., microbiota) in the development, health and ultimately survival of their host. This review targets the current knowledge on the bidirectional communication between the microbiota and the fish immune system during fish development. It explores the extent of this mutualistic relationship: on one hand, the effect that microbes exert on the immune system ontogeny of fishes, and on the other hand, the impact of critical steps in immune system development on the microbial recruitment and succession throughout their life. We will first describe the immune system and its ontogeny and gene expression steps in the immune system development of fishes. Secondly, the plurality of the microbiotas (depending on host organism, organ, and development stage) will be reviewed. Then, a description of the constant interactions between microbiota and immune system throughout the fish's life stages will be discussed. Healthy microbiotas allow immune system maturation and modulation of inflammation, both of which contribute to immune homeostasis. Thus, immune equilibrium is closely linked to microbiota stability and to the stages of microbial community succession during the host development. We will provide examples from several fish species and describe more extensively the mechanisms occurring in zebrafish model because immune system ontogeny is much more finely described for this species, thanks to the many existing zebrafish mutants which allow more precise investigations. We will conclude on how the conceptual framework associated to the research on the immune system will benefit from considering the relations between microbiota and immune system maturation. More precisely, the development of active tolerance of the microbiota from the earliest stages of life enables the sustainable establishment of a complex healthy microbial community in the adult host. Establishing a balanced host-microbiota interaction avoids triggering deleterious inflammation, and maintains immunological and microbiological homeostasis.
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Affiliation(s)
- Lisa Zoé Auclert
- Département de Biologie, Institut de Biologie Intégrative et des Systèmes, Université Laval, Québec, Canada
| | - Mousumi Sarker Chhanda
- Département de Biologie, Institut de Biologie Intégrative et des Systèmes, Université Laval, Québec, Canada
- Department of Aquaculture, Faculty of Fisheries, Hajee Mohammad Danesh Science and Technology University, Basherhat, Bangladesh
| | - Nicolas Derome
- Département de Biologie, Institut de Biologie Intégrative et des Systèmes, Université Laval, Québec, Canada
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8
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Prendecka-Wróbel M, Pigoń-Zając D, Sondej D, Grzywna K, Kamińska K, Szuta M, Małecka-Massalska T. Can Dietary Actives Affect miRNAs and Alter the Course or Prevent Colorectal Cancer? Int J Mol Sci 2023; 24:10142. [PMID: 37373289 DOI: 10.3390/ijms241210142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 06/12/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Colorectal cancer is a diet-related cancer. There is much research into the effects of nutrients on the prevention, modulation, and treatment of colorectal cancer. Researchers are trying to find a correlation between epidemiological observations indicating certain dietary components as the originator in the process of developing colorectal cancer, such as a diet rich in saturated animal fats, and dietary components that could eliminate the impact of harmful elements of the daily nutritional routine, i.e., substances such as polyunsaturated fatty acids, curcumin, or resveratrol. Nevertheless, it is very important to understand the mechanisms underlying how food works on cancer cells. In this case, microRNA (miRNA) seems to be a very significant research target. MiRNAs participate in many biological processes connected to carcinogenesis, progression, and metastasis. However, this is a field with development prospects ahead. In this paper, we review the most significant and well-studied food ingredients and their effects on various miRNAs involved in colorectal cancer.
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Affiliation(s)
- Monika Prendecka-Wróbel
- Department of Human Physiology of the Chair of Preclinical Sciences, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
| | - Dominika Pigoń-Zając
- Department of Human Physiology of the Chair of Preclinical Sciences, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
| | - Daria Sondej
- Department of Human Physiology of the Chair of Preclinical Sciences, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
| | - Karolina Grzywna
- Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Katarzyna Kamińska
- Department of Human Physiology of the Chair of Preclinical Sciences, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
| | - Mariusz Szuta
- Chair of Oral Surgery, Jagiellonian University Medical College, 31-155 Kraków, Poland
| | - Teresa Małecka-Massalska
- Department of Human Physiology of the Chair of Preclinical Sciences, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
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Mapelli-Brahm P, Gómez-Villegas P, Gonda ML, León-Vaz A, León R, Mildenberger J, Rebours C, Saravia V, Vero S, Vila E, Meléndez-Martínez AJ. Microalgae, Seaweeds and Aquatic Bacteria, Archaea, and Yeasts: Sources of Carotenoids with Potential Antioxidant and Anti-Inflammatory Health-Promoting Actions in the Sustainability Era. Mar Drugs 2023; 21:340. [PMID: 37367666 DOI: 10.3390/md21060340] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 05/25/2023] [Accepted: 05/27/2023] [Indexed: 06/28/2023] Open
Abstract
Carotenoids are a large group of health-promoting compounds used in many industrial sectors, such as foods, feeds, pharmaceuticals, cosmetics, nutraceuticals, and colorants. Considering the global population growth and environmental challenges, it is essential to find new sustainable sources of carotenoids beyond those obtained from agriculture. This review focuses on the potential use of marine archaea, bacteria, algae, and yeast as biological factories of carotenoids. A wide variety of carotenoids, including novel ones, were identified in these organisms. The role of carotenoids in marine organisms and their potential health-promoting actions have also been discussed. Marine organisms have a great capacity to synthesize a wide variety of carotenoids, which can be obtained in a renewable manner without depleting natural resources. Thus, it is concluded that they represent a key sustainable source of carotenoids that could help Europe achieve its Green Deal and Recovery Plan. Additionally, the lack of standards, clinical studies, and toxicity analysis reduces the use of marine organisms as sources of traditional and novel carotenoids. Therefore, further research on the processing of marine organisms, the biosynthetic pathways, extraction procedures, and examination of their content is needed to increase carotenoid productivity, document their safety, and decrease costs for their industrial implementation.
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Affiliation(s)
- Paula Mapelli-Brahm
- Food Colour and Quality Laboratory, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain
| | - Patricia Gómez-Villegas
- Laboratory of Biochemistry, Faculty of Experimental Sciences, Marine International Campus of Excellence and REMSMA, University of Huelva, 21071 Huelva, Spain
| | - Mariana Lourdes Gonda
- Área Microbiología, Departamento de Biociencias, Facultad de Química, Universidad de la República, Gral Flores 2124, Montevideo 11800, Uruguay
| | - Antonio León-Vaz
- Laboratory of Biochemistry, Faculty of Experimental Sciences, Marine International Campus of Excellence and REMSMA, University of Huelva, 21071 Huelva, Spain
| | - Rosa León
- Laboratory of Biochemistry, Faculty of Experimental Sciences, Marine International Campus of Excellence and REMSMA, University of Huelva, 21071 Huelva, Spain
| | | | | | - Verónica Saravia
- Departamento de Bioingeniería, Facultad de Ingeniería, Instituto de Ingeniería Química, Universidad de la República, Montevideo 11300, Uruguay
| | - Silvana Vero
- Área Microbiología, Departamento de Biociencias, Facultad de Química, Universidad de la República, Gral Flores 2124, Montevideo 11800, Uruguay
| | - Eugenia Vila
- Departamento de Bioingeniería, Facultad de Ingeniería, Instituto de Ingeniería Química, Universidad de la República, Montevideo 11300, Uruguay
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Ahrodia T, Kandiyal B, Das B. Microbiota and epigenetics: Health impact. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2023; 198:93-117. [PMID: 37225326 DOI: 10.1016/bs.pmbts.2023.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Epigenetic changes associated with disease development and progressions are of increasing importance because of their potential diagnostic and therapeutic applications. Several epigenetic changes associated with chronic metabolic disorders have been studied in various diseases. Epigenetic changes are mostly modulated by environmental factors, including the human microbiota living in different parts of our bodies. The microbial structural components and the microbially derived metabolites directly interact with host cells, thereby maintaining homeostasis. Microbiome dysbiosis, on the other hand, is known to produce elevated levels of disease-linked metabolites, which may directly affect a host metabolic pathway or induce epigenetic changes that can lead to disease development. Despite their important role in host physiology and signal transduction, there has been little research into the mechanics and pathways associated with epigenetic modifications. This chapter focuses on the relationship between microbes and their epigenetic effects in diseased pathology, as well as on the regulation and metabolism of the dietary options available to the microbes. Furthermore, this chapter also provides a prospective link between these two important phenomena, termed "Microbiome and Epigenetics."
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Affiliation(s)
- Taruna Ahrodia
- Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India
| | - Bharti Kandiyal
- Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India
| | - Bhabatosh Das
- Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.
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Epigenetic Modifications Induced by the Gut Microbiota May Result from What We Eat: Should We Talk about Precision Diet in Health and Disease? Metabolites 2023; 13:metabo13030375. [PMID: 36984815 PMCID: PMC10051796 DOI: 10.3390/metabo13030375] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/20/2023] [Accepted: 02/21/2023] [Indexed: 03/06/2023] Open
Abstract
Diet is currently considered one of the most important adjustable determinants of human health. The gut microbiota, the collection of microorganisms that inhabit (mainly) the distal bowel, has recently been shown to ensure critical physiological functions, such as immune, metabolic and neuropsychiatric. Many of these biological effects result from the production of bacterial metabolites that may target host cells, tissues and organs. In line with this rationale, epigenetics has brought new insights to our understanding of how environmental factors influence gene expression and, interestingly, gut microbiota metabolites have recently been proposed as novel and significant inducers of epigenetic modifications. Efforts have been dedicated to unveil how the production of specific metabolites influences the activity of epigenetic writers and erasers in order to establish a mechanistic link between gut microbiota, epigenetic modifications and health. Recent data is now evidencing how specific microbial metabolites shape the epigenetic landscape of eukaryotic cells, paving new avenues for innovative therapeutic strategies relying on diet-driven microbiota: epigenetic interactions. Herein is discussed the impact of diet on gut microbiota and the molecular mechanisms underlying microbiota–host interactions, highlighting the influence of diet on microbiota metabolome and how this may induce epigenetic modifications in host cells. Furthermore, it is hypothesized that epigenetics may be a key process transducing the effects of diet on gut microbiota with consequences for health and disease. Accordingly, innovating strategies of disease prevention based on a “precision diet”, a personalized dietary planning according to specific epigenetic targets, are discussed.
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Miyake M, Oda Y, Owari T, Iida K, Ohnishi S, Fujii T, Nishimura N, Miyamoto T, Shimizu T, Ohnishi K, Hori S, Morizawa Y, Gotoh D, Nakai Y, Torimoto K, Tanaka N, Fujimoto K. Probiotics enhances anti-tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer. Cancer Sci 2023; 114:1118-1130. [PMID: 36398663 PMCID: PMC9986082 DOI: 10.1111/cas.15666] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/04/2022] [Accepted: 11/15/2022] [Indexed: 11/19/2022] Open
Abstract
Chemotherapy drugs, such as gemcitabine and cisplatin (GC), are frequently administered to patients with advanced urothelial carcinoma, however the influence of the gut microbiota on their action is unclear. Thus, we investigated the effects of GC on the gut microbiome and determined whether oral supplementation with a probiotics mixture of Lactobacillus casei Shirota and Bifidobacterium breve enhanced the anti-tumor immune response. After subcutaneous inoculation with MBT2 murine bladder cancer cells, syngenic C3H mice were randomly allocated into eight groups. The gut microbiome cluster pattern was altered in both the GC and oral probiotics groups (p = 0.025). Both tumor-bearing conditions (no treatment) and GC chemotherapy influenced Pseudoclostridium, Robinsoniella, Merdimonas, and Phocea in the gut. Furthermore, comparison of the GC-treated and GC + probiotics groups revealed an association of four methyltransferase family enzymes and two short-change fatty acid-related enzymes with oral probiotics use. A significant difference in tumor volume was observed between the GC and GC + probiotics groups at week 2 of treatment. Additionally, decreased recruitment of cancer-associated fibroblasts and regulatory T cells, and activation of CD8+ T cells and dendritic cells were observed in the tumor microenvironment. Our findings reveal the positive effects of a probiotics mixture of Lactobacillus and Bifidobacterium in enhancing anti-tumor effects through the gut-tumor immune response axis. Future clinical trials are needed to evaluate the full benefits of this novel supplement with oral probiotics in patients with advanced urothelial carcinoma.
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Affiliation(s)
- Makito Miyake
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Yuki Oda
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Takuya Owari
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Kota Iida
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Sayuri Ohnishi
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Tomomi Fujii
- Diagnostic Pathology, Nara Medical University, Kashihara, Nara, Japan
| | | | - Tatsuki Miyamoto
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Takuto Shimizu
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Kenta Ohnishi
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Shunta Hori
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Yosuke Morizawa
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Daisuke Gotoh
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Yasushi Nakai
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Kazumasa Torimoto
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
| | - Nobumichi Tanaka
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan.,Prostate Brachytherapy, Nara Medical University, Kashihara, Nara, Japan
| | - Kiyohide Fujimoto
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
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13
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Maslova AY, Mishvelov AE, Nasrulaeva KN, Yasaeva JK, Tsgoev AS, Medova MM. Overview of the Pharmacological Use of Pectins and Pectin-Containing Substances: Recent Achievements and Prospects. PHARMACOPHORE 2023. [DOI: 10.51847/j34k56lsvr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/03/2023]
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14
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Lee BY, Ordovás JM, Parks EJ, Anderson CAM, Barabási AL, Clinton SK, de la Haye K, Duffy VB, Franks PW, Ginexi EM, Hammond KJ, Hanlon EC, Hittle M, Ho E, Horn AL, Isaacson RS, Mabry PL, Malone S, Martin CK, Mattei J, Meydani SN, Nelson LM, Neuhouser ML, Parent B, Pronk NP, Roche HM, Saria S, Scheer FAJL, Segal E, Sevick MA, Spector TD, Van Horn L, Varady KA, Voruganti VS, Martinez MF. Research gaps and opportunities in precision nutrition: an NIH workshop report. Am J Clin Nutr 2022; 116:1877-1900. [PMID: 36055772 PMCID: PMC9761773 DOI: 10.1093/ajcn/nqac237] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 04/06/2022] [Accepted: 08/30/2022] [Indexed: 02/01/2023] Open
Abstract
Precision nutrition is an emerging concept that aims to develop nutrition recommendations tailored to different people's circumstances and biological characteristics. Responses to dietary change and the resulting health outcomes from consuming different diets may vary significantly between people based on interactions between their genetic backgrounds, physiology, microbiome, underlying health status, behaviors, social influences, and environmental exposures. On 11-12 January 2021, the National Institutes of Health convened a workshop entitled "Precision Nutrition: Research Gaps and Opportunities" to bring together experts to discuss the issues involved in better understanding and addressing precision nutrition. The workshop proceeded in 3 parts: part I covered many aspects of genetics and physiology that mediate the links between nutrient intake and health conditions such as cardiovascular disease, Alzheimer disease, and cancer; part II reviewed potential contributors to interindividual variability in dietary exposures and responses such as baseline nutritional status, circadian rhythm/sleep, environmental exposures, sensory properties of food, stress, inflammation, and the social determinants of health; part III presented the need for systems approaches, with new methods and technologies that can facilitate the study and implementation of precision nutrition, and workforce development needed to create a new generation of researchers. The workshop concluded that much research will be needed before more precise nutrition recommendations can be achieved. This includes better understanding and accounting for variables such as age, sex, ethnicity, medical history, genetics, and social and environmental factors. The advent of new methods and technologies and the availability of considerably more data bring tremendous opportunity. However, the field must proceed with appropriate levels of caution and make sure the factors listed above are all considered, and systems approaches and methods are incorporated. It will be important to develop and train an expanded workforce with the goal of reducing health disparities and improving precision nutritional advice for all Americans.
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Affiliation(s)
- Bruce Y Lee
- Health Policy and Management, City University of New York Graduate School of Public Health and Health Policy, New York, NY, USA
| | - José M Ordovás
- USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - Elizabeth J Parks
- Nutrition and Exercise Physiology, University of Missouri School of Medicine, MO, USA
| | | | - Albert-László Barabási
- Network Science Institute and Department of Physics, Northeastern University, Boston, MA, USA
| | | | - Kayla de la Haye
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Valerie B Duffy
- Allied Health Sciences, University of Connecticut, Storrs, CT, USA
| | - Paul W Franks
- Novo Nordisk Foundation, Hellerup, Denmark, Copenhagen, Denmark, and Lund University Diabetes Center, Sweden
- The Lund University Diabetes Center, Malmo, SwedenInsert Affiliation Text Here
| | - Elizabeth M Ginexi
- National Institutes of Health, Office of Behavioral and Social Sciences Research, Bethesda, MD, USA
| | - Kristian J Hammond
- Computer Science, Northwestern University McCormick School of Engineering, IL, USA
| | - Erin C Hanlon
- Department of Medicine, The University of Chicago, Chicago, IL, USA
| | - Michael Hittle
- Epidemiology and Clinical Research, Stanford University, Stanford, CA, USA
| | - Emily Ho
- Public Health and Human Sciences, Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
| | - Abigail L Horn
- Information Sciences Institute, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA
| | | | | | - Susan Malone
- Rory Meyers College of Nursing, New York University, New York, NY, USA
| | - Corby K Martin
- Ingestive Behavior Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA
| | - Josiemer Mattei
- Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Simin Nikbin Meydani
- USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - Lorene M Nelson
- Epidemiology and Population Health, Stanford University, Stanford, CA, USA
| | | | - Brendan Parent
- Grossman School of Medicine, New York University, New York, NY, USA
| | | | - Helen M Roche
- UCD Conway Institute, School of Public Health, Physiotherapy, and Sports Science, University College Dublin, Dublin, Ireland
| | - Suchi Saria
- Johns Hopkins University, Baltimore, MD, USA
| | - Frank A J L Scheer
- Brigham and Women's Hospital, Boston, MA, USA
- Medicine and Neurology, Harvard Medical School, Boston, MA, USA
| | - Eran Segal
- Computer Science and Applied Math, Weizmann Institute of Science, Rehovot, Israel
| | - Mary Ann Sevick
- Grossman School of Medicine, New York University, New York, NY, USA
| | - Tim D Spector
- Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
| | - Linda Van Horn
- Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Krista A Varady
- Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, USA
| | - Venkata Saroja Voruganti
- Nutrition and Nutrition Research Institute, Gillings School of Public Health, The University of North Carolina, Chapel Hill, NC, USA
| | - Marie F Martinez
- Health Policy and Management, City University of New York Graduate School of Public Health and Health Policy, New York, NY, USA
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15
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Dietary polyphenols and their relationship to the modulation of non-communicable chronic diseases and epigenetic mechanisms: A mini-review. FOOD CHEMISTRY. MOLECULAR SCIENCES 2022; 6:100155. [PMID: 36582744 PMCID: PMC9793217 DOI: 10.1016/j.fochms.2022.100155] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 10/18/2022] [Accepted: 12/11/2022] [Indexed: 12/14/2022]
Abstract
Chronic Non-Communicable Diseases (NCDs) have been considered a global health problem, characterized as diseases of multiple factors, which are developed throughout life, and regardless of genetics as a risk factor of important relevance, the increase in mortality attributed to the disease to environmental factors and the lifestyle one leads. Although the reactive species (ROS/RNS) are necessary for several physiological processes, their overproduction is directly related to the pathogenesis and aggravation of NCDs. In contrast, dietary polyphenols have been widely associated with minimizing oxidative stress and inflammation. In addition to their antioxidant power, polyphenols have also drawn attention for being able to modulate both gene expression and modify epigenetic alterations, suggesting an essential involvement in the prevention and/or development of some pathologies. Therefore, this review briefly explained the mechanisms in the development of some NCDs, followed by a summary of some evidence related to the interaction of polyphenols in oxidative stress, as well as the modulation of epigenetic mechanisms involved in the management of NCDs.
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Key Words
- 8-oxodG, 8-oxo-2́deosyguanosine
- ABCG, ATP Binding Cassette Subfamily G Member
- ADAM10, α-secretase
- ADRB3, adrenoceptor Beta 3
- APP, amyloid-β precursor protein
- ARF, auxin response factor
- ARH-I, aplysia ras homology member I
- ARHGAP24, Rho GTPase Activating Protein 24
- ATF6, activating transcription factor 6
- ATP2A3, ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 3
- BCL2L14, apoptosis facilitator Bcl-2-like protein 14
- Bioactive compounds
- CDH1, cadherin-1
- CDKN, cyclin dependent kinase inhibitor
- CPT, carnitine palmitoyltransferase
- CREBH, cyclic AMP-responsive element-binding protein H
- DANT2, DXZ4 associated non-noding transcript 2, distal
- DAPK1, death-associated protein kinase 1
- DNA methylation
- DNMT, DNA methyltransferase
- DOT1L, disruptor of telomeric silencing 1-like
- EWASs, epigenome-wide association studies
- EZH2, Enhancer of zeste homolog 2
- FAS, Fas cell Surface Death Receptor
- GDNF, glial cell line-derived neurotrophic factor
- GFAP, glial fibrillary acid protein
- GSTP1, Glutathione S-transferases P1
- Gut microbiota modulation
- HAT, histone acetylases
- HDAC, histone deacetylases
- HSD11B2, 11 beta-hydroxysteroid dehydrogenase type 2
- Histone modifications
- IGFBP3, insulin-like growth factor-binding protein 3
- IGT, impaired glucose tolerance
- KCNK3, potassium two pore domain channel subfamily K Member 3
- MBD4, methyl-CpG binding domain 4
- MGMT, O-6-methylguanine-DNA methyltransferase
- NAFLD, Non-alcoholic fatty liver disease
- OCT1, Organic cation transporter 1
- OGG1, 8-Oxoguanine DNA Glycosylase
- Oxidative stress
- PAI-1, plasminogen activator inhibitor 1
- PHOSPHO1, Phosphoethanolamine/Phosphocholine Phosphatase 1
- PLIN1, perilipin 1
- POE3A, RNA polymerase III
- PPAR, peroxisome proliferator-activated receptor
- PPARGC1A, PPARG coactivator 1 alpha
- PRKCA, Protein kinase C alpha
- PTEN, phosphatase and tensin homologue
- Personalized nutrition
- RASSF1A, Ras association domain family member 1
- SAH, S -adenosyl-l-homocysteine
- SAM, S-adenosyl-methionine
- SD, sleep deprivation
- SOCS3, suppressor of cytokine signaling 3
- SREBP-1C, sterol-regulatory element binding protein-1C
- TBX2, t-box transcription factor 2
- TCF7L2, transcription factor 7 like 2
- TET, ten-eleven translocation proteins
- TNNT2, cardiac muscle troponin T
- TPA, 12-O-tetradecanoylphorbol-13-acetate
- lncRNA, long non-coding RNA
- ncRNA, non-coding RNA
- oAβ-induced-LTP, oligomeric amyloid-beta induced long term potentiation
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16
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Marín-Tello C, Jintaridth P, Sanchez F, González C, Zelada-Castillo L, Vásquez-Arqueros A, Guevara-Vásquez A, Vieira A. Epigenetic regulation by metabolites from the gut microbiome. Benef Microbes 2022; 13:437-444. [PMID: 36377583 DOI: 10.3920/bm2022.0006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The gut microbiome can metabolise food components, such as dietary fibres and various phytochemicals; and the microbiome can also synthesise some nutrients, for example B vitamins. The metabolites produced by bacteria and other micro-organisms in the colon can have implications for health and disease risk. Some of these metabolites are epigenetically active, and can contribute to changes in the chemical modification and structure of chromatin by affecting the activity and expression of epigenetically-active enzymes, for example histone deacetylases and DNA methyltransferases. The epigenetic activity of such gut microbiome metabolites is reviewed herein.
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Affiliation(s)
- C Marín-Tello
- Food, Metabolism, and Physiology Laboratory, Facultad de Farmacia y Bioquímica, Universidad Nacional de Trujillo, Trujillo 13008, Perú
| | - P Jintaridth
- Department of Tropical Nutrition and Food Science, The Faculty of Tropical Medicine, Mahidol University, 420/6 Rachavithi Road, Rachathevi, Payatai, Bangkok 10400, Thailand
| | - F Sanchez
- Instituto De Educacion Superior Tecnológico Público, 103, Lonya Grande 01556, Perú
| | - C González
- CITE Agroindustrial Chavimochic, Virú 044, Perú
| | - L Zelada-Castillo
- Food, Metabolism, and Physiology Laboratory, Facultad de Farmacia y Bioquímica, Universidad Nacional de Trujillo, Trujillo 13008, Perú
| | - A Vásquez-Arqueros
- Food, Metabolism, and Physiology Laboratory, Facultad de Farmacia y Bioquímica, Universidad Nacional de Trujillo, Trujillo 13008, Perú
| | - A Guevara-Vásquez
- Food, Metabolism, and Physiology Laboratory, Facultad de Farmacia y Bioquímica, Universidad Nacional de Trujillo, Trujillo 13008, Perú
| | - A Vieira
- Nutrition and Metabolism Research Laboratory, BPK-9625, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada
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17
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Nuwaylati D, Eldakhakhny B, Bima A, Sakr H, Elsamanoudy A. Low-Carbohydrate High-Fat Diet: A SWOC Analysis. Metabolites 2022; 12:1126. [PMID: 36422267 PMCID: PMC9695571 DOI: 10.3390/metabo12111126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 11/14/2022] [Accepted: 11/15/2022] [Indexed: 08/27/2023] Open
Abstract
Insulin resistance (IR) plays a role in the pathogenesis of many diseases, such as type 2 diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, obesity, and neurodegenerative diseases, including Alzheimer's disease. The ketogenic diet (KD) is a low-carbohydrate/high-fat diet that arose in the 1920s as an effective treatment for seizure control. Since then, the KD has been studied as a therapeutic approach for various IR-related disorders with successful results. To date, the use of the KD is still debatable regarding its safety. Some studies have acknowledged its usefulness, while others do not recommend its long-term implementation. In this review, we applied a SWOC (Strengths, Weaknesses, Opportunities, and Challenges) analysis that revealed the positive, constructive strengths of the KD, its potential complications, different conditions that can make used for it, and the challenges faced by both physicians and subjects throughout a KD. This SWOC analysis showed that the KD works on the pathophysiological mechanism of IR-related disorders such as chronic inflammation, oxidative stress and mitochondrial stress. Furthermore, the implementation of the KD as a potential adjuvant therapy for many diseases, including cancer, neurodegenerative disorders, polycystic ovary syndrome, and pain management was proven. On the other hand, the short and long-term possible undesirable KD-related effects, including nutritional deficiencies, growth retardation and nephrolithiasis, should be considered and strictly monitored. Conclusively, this review provides a context for decision-makers, physicians, researchers, and the general population to focus on this dietary intervention in preventing and treating diseases. Moreover, it draws the attention of scientists and physicians towards the opportunities and challenges associated with the KD that requires attention before KD initiation.
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Affiliation(s)
- Dena Nuwaylati
- Clinical Biochemistry Department, Faculty of Medicine, University of Jeddah, Jeddah 21959, Saudi Arabia
| | - Basmah Eldakhakhny
- Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia
| | - Abdulhadi Bima
- Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia
| | - Hussein Sakr
- Physiology Department, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
- Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Ayman Elsamanoudy
- Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
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18
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Ramos-Lopez O, Martinez JA, Milagro FI. Holistic Integration of Omics Tools for Precision Nutrition in Health and Disease. Nutrients 2022; 14:4074. [PMID: 36235725 PMCID: PMC9572439 DOI: 10.3390/nu14194074] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 09/23/2022] [Accepted: 09/29/2022] [Indexed: 11/16/2022] Open
Abstract
The combination of multiple omics approaches has emerged as an innovative holistic scope to provide a more comprehensive view of the molecular and physiological events underlying human diseases (including obesity, dyslipidemias, fatty liver, insulin resistance, and inflammation), as well as for elucidating unique and specific metabolic phenotypes. These omics technologies include genomics (polymorphisms and other structural genetic variants), epigenomics (DNA methylation, histone modifications, long non-coding RNA, telomere length), metagenomics (gut microbiota composition, enterotypes), transcriptomics (RNA expression patterns), proteomics (protein quantities), and metabolomics (metabolite profiles), as well as interactions with dietary/nutritional factors. Although more evidence is still necessary, it is expected that the incorporation of integrative omics could be useful not only for risk prediction and early diagnosis but also for guiding tailored dietary treatments and prognosis schemes. Some challenges include ethical and regulatory issues, the lack of robust and reproducible results due to methodological aspects, the high cost of omics methodologies, and high-dimensional data analyses and interpretation. In this review, we provide examples of system biology studies using multi-omics methodologies to unravel novel insights into the mechanisms and pathways connecting the genotype to clinically relevant traits and therapy outcomes for precision nutrition applications in health and disease.
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Affiliation(s)
- Omar Ramos-Lopez
- Medicine and Psychology School, Autonomous University of Baja California, Tijuana 22390, Mexico
| | - J. Alfredo Martinez
- Precision Nutrition and Cardiometabolic Health, IMDEA Food Institute, CEI UAM+CSIC, 28049 Madrid, Spain
| | - Fermin I. Milagro
- Department of Nutrition, Food Sciences and Physiology, University of Navarra, 31008 Pamplona, Spain
- Center for Nutrition Research, University of Navarra, 31008 Pamplona, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Institute of Health Carlos III, 28029 Madrid, Spain
- Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain
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19
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Novel epigenetic therapeutic strategies and targets in cancer. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166552. [PMID: 36126898 DOI: 10.1016/j.bbadis.2022.166552] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 09/08/2022] [Accepted: 09/14/2022] [Indexed: 11/24/2022]
Abstract
The critical role of dysregulated epigenetic pathways in cancer genesis, development, and therapy has typically been established as a result of scientific and technical innovations in next generation sequencing. RNA interference, histone modification, DNA methylation and chromatin remodelling are epigenetic processes that control gene expression without causing mutations in the DNA. Although epigenetic abnormalities are thought to be a symptom of cell tumorigenesis and malignant events that impact tumor growth and drug resistance, physicians believe that related processes might be a key therapeutic target for cancer treatment and prevention due to the reversible nature of these processes. A plethora of novel strategies for addressing epigenetics in cancer therapy for immuno-oncological complications are currently available - ranging from basic treatment to epigenetic editing. - and they will be the subject of this comprehensive review. In this review, we cover most of the advancements made in the field of targeting epigenetics with special emphasis on microbiology, plasma science, biophysics, pharmacology, molecular biology, phytochemistry, and nanoscience.
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20
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Wang L, Zhang W, Wu X, Liang X, Cao L, Zhai J, Yang Y, Chen Q, Liu H, Zhang J, Ding Y, Zhu F, Tang J. MIAOME: Human Microbiome Affect The Host Epigenome. Comput Struct Biotechnol J 2022; 20:2455-2463. [PMID: 35664224 PMCID: PMC9136154 DOI: 10.1016/j.csbj.2022.05.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 05/11/2022] [Accepted: 05/12/2022] [Indexed: 01/10/2023] Open
Abstract
Besides the genetic factors having tremendous influences on the regulations of the epigenome, the microenvironmental factors have recently gained extensive attention for their roles in affecting the host epigenome. There are three major types of microenvironmental factors: microbiota-derived metabolites (MDM), microbiota-derived components (MDC) and microbiota-secreted proteins (MSP). These factors can regulate host physiology by modifying host gene expression through the three highly interconnected epigenetic mechanisms (e.g. histone modifications, DNA modifications, and non-coding RNAs). However, no database was available to provide the comprehensive factors of these types. Herein, a database entitled 'Human Microbiome Affect The Host Epigenome (MIAOME)' was constructed. Based on the types of epigenetic modifications confirmed in the literature review, the MIAOME database captures 1068 (63 genus, 281 species, 707 strains, etc.) human microbes, 91 unique microbiota-derived metabolites & components (16 fatty acids, 10 bile acids, 10 phenolic compounds, 10 vitamins, 9 tryptophan metabolites, etc.) derived from 967 microbes; 50 microbes that secreted 40 proteins; 98 microbes that directly influence the host epigenetic modification, and provides 3 classifications of the epigenome, including (1) 4 types of DNA modifications, (2) 20 histone modifications and (3) 490 ncRNAs regulations, involved in 160 human diseases. All in all, MIAOME has compiled the information on the microenvironmental factors influence host epigenome through the scientific literature and biochemical databases, and allows the collective considerations among the different types of factors. It can be freely assessed without login requirement by all users at: http://miaome.idrblab.net/ttd/
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Affiliation(s)
- Lidan Wang
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Wei Zhang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Xianglu Wu
- Joint International Research Laboratory of Reproductive and Development, Department of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Xiao Liang
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Lijie Cao
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Jincheng Zhai
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Yiyang Yang
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Qiuxiao Chen
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Hongqing Liu
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Jun Zhang
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Yubin Ding
- Joint International Research Laboratory of Reproductive and Development, Department of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, China
- Corresponding authors at: School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China (J. Tang).
| | - Feng Zhu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Corresponding authors at: School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China (J. Tang).
| | - Jing Tang
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
- Joint International Research Laboratory of Reproductive and Development, Department of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, China
- Corresponding authors at: School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China (J. Tang).
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21
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Monaghan TM, Polytarchou C, Kao D, Alexander C, Gurnani P. Therapeutic potential of miRNAs in Clostridioides difficile infection. Future Microbiol 2022; 17:315-318. [PMID: 35172603 DOI: 10.2217/fmb-2021-0311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Tweetable abstract Treating Clostridioides difficile infection with miRNAs alone or combined with live biotherapeutic products may augment therapeutic efficacy and help counteract drug resistance in the future.
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Affiliation(s)
- Tanya M Monaghan
- National Institute for Health Research Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, NG7 2UH, UK.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, NG7 2UH, UK
| | - Christos Polytarchou
- Department of Biosciences, John van Geest Cancer Research Centre, School of Science & Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK.,Centre for Health, Aging & Understanding Disease, School of Science & Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK
| | - Dina Kao
- Department of Medicine, University of Alberta, Edmonton, AB, T6G 2G3, Canada
| | - Cameron Alexander
- Division of Molecular Therapeutics & Formulation, School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK
| | - Pratik Gurnani
- Division of Molecular Therapeutics & Formulation, School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK
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22
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Gong QY, Cai L, Jing Y, Wang W, Yang DX, Chen SW, Tian HL. Urolithin A alleviates blood-brain barrier disruption and attenuates neuronal apoptosis following traumatic brain injury in mice. Neural Regen Res 2022; 17:2007-2013. [PMID: 35142690 PMCID: PMC8848621 DOI: 10.4103/1673-5374.335163] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Urolithin A (UA) is a natural metabolite produced from polyphenolics in foods such as pomegranates, berries, and nuts. UA is neuroprotective against Parkinson's disease, Alzheimer's disease, and cerebral hemorrhage. However, its effect against traumatic brain injury remains unknown. In this study, we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA. We found that UA greatly reduced brain edema; increased the expression of tight junction proteins in injured cortex; increased the immunopositivity of two neuronal autophagy markers, microtubule-associated protein 1A/B light chain 3A/B (LC3) and p62; downregulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR), two regulators of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling pathway; decreased the phosphorylation levels of inhibitor of NFκB (IκB) kinase alpha (IKKα) and nuclear factor kappa B (NFκB), two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway; reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex; and improved mouse neurological function. These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury, and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways, thus reducing neuroinflammation and enhancing autophagy.
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Affiliation(s)
- Qiu-Yuan Gong
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Lin Cai
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Yao Jing
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Wei Wang
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Dian-Xu Yang
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Shi-Wen Chen
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Heng-Li Tian
- Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
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23
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Deng Y, Kokou F, Eding EH, Verdegem MCJ. Impact of early-life rearing history on gut microbiome succession and performance of Nile tilapia. Anim Microbiome 2021; 3:81. [PMID: 34838149 PMCID: PMC8627003 DOI: 10.1186/s42523-021-00145-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/15/2021] [Indexed: 12/16/2022] Open
Abstract
Background Fish gut microbial colonisation starts during larval stage and plays an important role in host’s growth and health. To what extent first colonisation could influence the gut microbiome succession and growth in later life remains unknown. In this study, Nile tilapia embryos were incubated in two different environments, a flow-through system (FTS) and a biofloc system (BFS); hatched larvae were subsequently cultured in the systems for 14 days of feeding (dof). Fish were then transferred to one common recirculating aquaculture system (RAS1, common garden, 15–62 dof), followed by a growth trial in another RAS (RAS2, growth trial, 63–105 dof). In RAS2, fish were fed with two types of diet, differing in non-starch polysaccharide content. Our aim was to test the effect of rearing environment on the gut microbiome development, nutrient digestibility and growth performance of Nile tilapia during post-larvae stages. Results Larvae cultured in the BFS showed better growth and different gut microbiome, compared to FTS. After the common garden, the gut microbiome still showed differences in species composition, while body weight was similar. Long-term effects of early life rearing history on fish gut microbiome composition, nutrient digestibility, nitrogen and energy balances were not observed. Still, BFS-reared fish had more gut microbial interactions than FTS-reared fish. A temporal effect was observed in gut microbiome succession during fish development, although a distinct number of core microbiome remained present throughout the experimental period. Conclusion Our results indicated that the legacy effect of first microbial colonisation of the fish gut gradually disappeared during host development, with no differences in gut microbiome composition and growth performance observed in later life after culture in a common environment. However, early life exposure of larvae to biofloc consistently increased the microbial interactions in the gut of juvenile Nile tilapia and might possibly benefit gut health. Supplementary Information The online version contains supplementary material available at 10.1186/s42523-021-00145-w.
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Affiliation(s)
- Yale Deng
- Aquaculture and Fisheries Group, Wageningen University and Research, Wageningen, The Netherlands
| | - Fotini Kokou
- Aquaculture and Fisheries Group, Wageningen University and Research, Wageningen, The Netherlands.
| | - Ep H Eding
- Aquaculture and Fisheries Group, Wageningen University and Research, Wageningen, The Netherlands
| | - Marc C J Verdegem
- Aquaculture and Fisheries Group, Wageningen University and Research, Wageningen, The Netherlands
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24
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Guz M, Jeleniewicz W, Malm A, Korona-Glowniak I. A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer. Nutrients 2021; 13:2428. [PMID: 34371938 PMCID: PMC8308570 DOI: 10.3390/nu13072428] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 07/09/2021] [Accepted: 07/13/2021] [Indexed: 02/07/2023] Open
Abstract
A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.
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Affiliation(s)
- Małgorzata Guz
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland;
| | - Witold Jeleniewicz
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland;
| | - Anna Malm
- Department of Pharmaceutical Microbiology, Medical University of Lublin, 20-093 Lublin, Poland; (A.M.); (I.K.-G.)
| | - Izabela Korona-Glowniak
- Department of Pharmaceutical Microbiology, Medical University of Lublin, 20-093 Lublin, Poland; (A.M.); (I.K.-G.)
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25
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Wu Y, Wang CZ, Wan JY, Yao H, Yuan CS. Dissecting the Interplay Mechanism between Epigenetics and Gut Microbiota: Health Maintenance and Disease Prevention. Int J Mol Sci 2021; 22:6933. [PMID: 34203243 PMCID: PMC8267743 DOI: 10.3390/ijms22136933] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/10/2021] [Accepted: 06/24/2021] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota exists throughout the full life cycle of the human body, and it has been proven to have extensive impacts on health and disease. Accumulating evidence demonstrates that the interplay between gut microbiota and host epigenetics plays a multifaceted role in health maintenance and disease prevention. Intestinal microflora, along with their metabolites, could regulate multiple epigenetic pathways; e.g., DNA methylation, miRNA, or histone modification. Moreover, epigenetic factors can serve as mediators to coordinate gut microbiota within the host. Aiming to dissect this interplay mechanism, the present review summarizes the research profile of gut microbiota and epigenetics in detail, and further interprets the biofunctions of this interplay, especially the regulation of intestinal inflammation, the improvement of metabolic disturbances, and the inhibition of colitis events. This review provides new insights into the interplay of epigenetics and gut microbiota, and attempts to reveal the mysteries of health maintenance and disease prevention from this new perspective.
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Affiliation(s)
- Yuqi Wu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China;
- National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Chong-Zhi Wang
- Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, IL 60637, USA; (C.-Z.W.); (C.-S.Y.)
- Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL 60637, USA
| | - Jin-Yi Wan
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China;
- National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Haiqiang Yao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China;
- National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Chun-Su Yuan
- Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, IL 60637, USA; (C.-Z.W.); (C.-S.Y.)
- Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL 60637, USA
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26
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Caffaratti C, Plazy C, Mery G, Tidjani AR, Fiorini F, Thiroux S, Toussaint B, Hannani D, Le Gouellec A. What We Know So Far about the Metabolite-Mediated Microbiota-Intestinal Immunity Dialogue and How to Hear the Sound of This Crosstalk. Metabolites 2021; 11:406. [PMID: 34205653 PMCID: PMC8234899 DOI: 10.3390/metabo11060406] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/15/2021] [Accepted: 06/16/2021] [Indexed: 12/25/2022] Open
Abstract
Trillions of microorganisms, termed the "microbiota", reside in the mammalian gastrointestinal tract, and collectively participate in regulating the host phenotype. It is now clear that the gut microbiota, metabolites, and intestinal immune function are correlated, and that alterations of the complex and dynamic host-microbiota interactions can have deep consequences for host health. However, the mechanisms by which the immune system regulates the microbiota and by which the microbiota shapes host immunity are still not fully understood. This article discusses the contribution of metabolites in the crosstalk between gut microbiota and immune cells. The identification of key metabolites having a causal effect on immune responses and of the mechanisms involved can contribute to a deeper insight into host-microorganism relationships. This will allow a better understanding of the correlation between dysbiosis, microbial-based dysmetabolism, and pathogenesis, thus creating opportunities to develop microbiota-based therapeutics to improve human health. In particular, we systematically review the role of soluble and membrane-bound microbial metabolites in modulating host immunity in the gut, and of immune cells-derived metabolites affecting the microbiota, while discussing evidence of the bidirectional impact of this crosstalk. Furthermore, we discuss the potential strategies to hear the sound of such metabolite-mediated crosstalk.
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Affiliation(s)
- Clément Caffaratti
- Faculty of Medicine, CNRS, Grenoble INP, CHU Grenoble-Alpes, University Grenoble Alpes, TIMC (UMR5525), 38000 Grenoble, France; (C.C.); (C.P.); (G.M.); (A.-R.T.); (S.T.); (B.T.)
| | - Caroline Plazy
- Faculty of Medicine, CNRS, Grenoble INP, CHU Grenoble-Alpes, University Grenoble Alpes, TIMC (UMR5525), 38000 Grenoble, France; (C.C.); (C.P.); (G.M.); (A.-R.T.); (S.T.); (B.T.)
- Service de Biochimie Biologie Moléculaire Toxicologie Environnementale, UM Biochimie des Enzymes et des Protéines, Institut de Biologie et Pathologie, CHU Grenoble-Alpes, 38000 Grenoble, France
- Plateforme de Métabolomique GEMELI-GExiM, Institut de Biologie et Pathologie, CHU Grenoble-Alpes, 38000 Grenoble, France;
| | - Geoffroy Mery
- Faculty of Medicine, CNRS, Grenoble INP, CHU Grenoble-Alpes, University Grenoble Alpes, TIMC (UMR5525), 38000 Grenoble, France; (C.C.); (C.P.); (G.M.); (A.-R.T.); (S.T.); (B.T.)
- Department of Infectiology-Pneumology, CHU Grenoble-Alpes, 38000 Grenoble, France
| | - Abdoul-Razak Tidjani
- Faculty of Medicine, CNRS, Grenoble INP, CHU Grenoble-Alpes, University Grenoble Alpes, TIMC (UMR5525), 38000 Grenoble, France; (C.C.); (C.P.); (G.M.); (A.-R.T.); (S.T.); (B.T.)
| | - Federica Fiorini
- Plateforme de Métabolomique GEMELI-GExiM, Institut de Biologie et Pathologie, CHU Grenoble-Alpes, 38000 Grenoble, France;
| | - Sarah Thiroux
- Faculty of Medicine, CNRS, Grenoble INP, CHU Grenoble-Alpes, University Grenoble Alpes, TIMC (UMR5525), 38000 Grenoble, France; (C.C.); (C.P.); (G.M.); (A.-R.T.); (S.T.); (B.T.)
| | - Bertrand Toussaint
- Faculty of Medicine, CNRS, Grenoble INP, CHU Grenoble-Alpes, University Grenoble Alpes, TIMC (UMR5525), 38000 Grenoble, France; (C.C.); (C.P.); (G.M.); (A.-R.T.); (S.T.); (B.T.)
- Service de Biochimie Biologie Moléculaire Toxicologie Environnementale, UM Biochimie des Enzymes et des Protéines, Institut de Biologie et Pathologie, CHU Grenoble-Alpes, 38000 Grenoble, France
- Plateforme de Métabolomique GEMELI-GExiM, Institut de Biologie et Pathologie, CHU Grenoble-Alpes, 38000 Grenoble, France;
| | - Dalil Hannani
- Faculty of Medicine, CNRS, Grenoble INP, CHU Grenoble-Alpes, University Grenoble Alpes, TIMC (UMR5525), 38000 Grenoble, France; (C.C.); (C.P.); (G.M.); (A.-R.T.); (S.T.); (B.T.)
| | - Audrey Le Gouellec
- Faculty of Medicine, CNRS, Grenoble INP, CHU Grenoble-Alpes, University Grenoble Alpes, TIMC (UMR5525), 38000 Grenoble, France; (C.C.); (C.P.); (G.M.); (A.-R.T.); (S.T.); (B.T.)
- Service de Biochimie Biologie Moléculaire Toxicologie Environnementale, UM Biochimie des Enzymes et des Protéines, Institut de Biologie et Pathologie, CHU Grenoble-Alpes, 38000 Grenoble, France
- Plateforme de Métabolomique GEMELI-GExiM, Institut de Biologie et Pathologie, CHU Grenoble-Alpes, 38000 Grenoble, France;
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27
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López de Las Hazas MC, Gil-Zamorano J, Cofán M, Mantilla-Escalante DC, Garcia-Ruiz A, Del Pozo-Acebo L, Pastor O, Yañez-Mo M, Mazzeo C, Serra-Mir M, Doménech M, Valls-Pedret C, Rajaram S, Sabaté J, Ros E, Sala-Vila A, Dávalos A. One-year dietary supplementation with walnuts modifies exosomal miRNA in elderly subjects. Eur J Nutr 2021; 60:1999-2011. [PMID: 32979076 DOI: 10.1007/s00394-020-02390-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 09/14/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE Epidemiological studies and clinical trials support the association of nut consumption with a lower risk of prevalent non-communicable diseases, particularly cardiovascular disease. However, the molecular mechanisms underlying nut benefits remain to be fully described. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and play a pivotal role in health and disease. Exosomes are extracellular vesicles released from cells and mediate intercellular communication. Whether nut consumption modulates circulating miRNAs (c-miRNAs) transported in exosomes is poorly described. METHODS Cognitively healthy elderly subjects were randomized to either control (n = 110, abstaining from walnuts) or daily supplementation with walnuts (15% of their total energy, ≈30-60 g/day, n = 101) for 1-year. C-miRNAs were screened in exosomes isolated from 10 samples, before and after supplementation, and identified c-miRNA candidates were validated in the whole cohort. In addition, nanoparticle tracking analysis and lipidomics were assessed in pooled exosomes from the whole cohort. RESULTS Exosomal hsa-miR-32-5p and hsa-miR-29b-3p were consistently induced by walnut consumption. No major changes in exosomal lipids, nanoparticle concentration or size were found. CONCLUSION Our results provide novel evidence that certain c-miRNAs transported in exosomes are modulated by walnut consumption. The extent to which this finding contributes to the benefits of walnuts deserves further research.
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Affiliation(s)
- María-Carmen López de Las Hazas
- Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain
| | - Judit Gil-Zamorano
- Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain
| | - Montserrat Cofán
- Lipid Clinic, Endocrinology and Nutrition Service, Institut d´Investigacions Biomèdiques August Pi i Sunyer, 08036, Barcelona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain
| | - Diana C Mantilla-Escalante
- Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain
| | - Almudena Garcia-Ruiz
- Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain
| | - Lorena Del Pozo-Acebo
- Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain
| | - Oscar Pastor
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain
- Servicio de Bioquímica Clínica (UCA-CCM), Hospital Ramón y Cajal-IRYCIS, 28034, Madrid, Spain
| | - María Yañez-Mo
- Department of Molecular Biology, UAM, 28049, Madrid, Spain
- Centro de Biología Molecular Severo Ochoa (CBM-SO), Instituto de Investigación Sanitaria Princesa (IIS-IP), 28049, Madrid, Spain
| | - Carla Mazzeo
- Department of Molecular Biology, UAM, 28049, Madrid, Spain
- Centro de Biología Molecular Severo Ochoa (CBM-SO), Instituto de Investigación Sanitaria Princesa (IIS-IP), 28049, Madrid, Spain
| | - Mercè Serra-Mir
- Lipid Clinic, Endocrinology and Nutrition Service, Institut d´Investigacions Biomèdiques August Pi i Sunyer, 08036, Barcelona, Spain
| | - Monica Doménech
- Lipid Clinic, Endocrinology and Nutrition Service, Institut d´Investigacions Biomèdiques August Pi i Sunyer, 08036, Barcelona, Spain
| | - Cinta Valls-Pedret
- Lipid Clinic, Endocrinology and Nutrition Service, Institut d´Investigacions Biomèdiques August Pi i Sunyer, 08036, Barcelona, Spain
| | - Sujatha Rajaram
- Center for Nutrition, Healthy Lifestyle and Disease Prevention, School of Public Health, Loma Linda University, Loma Linda, CA, 92350, USA
| | - Joan Sabaté
- Center for Nutrition, Healthy Lifestyle and Disease Prevention, School of Public Health, Loma Linda University, Loma Linda, CA, 92350, USA
| | - Emilio Ros
- Lipid Clinic, Endocrinology and Nutrition Service, Institut d´Investigacions Biomèdiques August Pi i Sunyer, 08036, Barcelona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain
| | - Aleix Sala-Vila
- Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, 08003, Spain.
- Hospital del Mar Medical Research Institute, IMIM, Dr. Aiguader 88, 08003, Barcelona, Spain.
| | - Alberto Dávalos
- Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
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28
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Dowis K, Banga S. The Potential Health Benefits of the Ketogenic Diet: A Narrative Review. Nutrients 2021; 13:nu13051654. [PMID: 34068325 PMCID: PMC8153354 DOI: 10.3390/nu13051654] [Citation(s) in RCA: 98] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 04/30/2021] [Accepted: 05/09/2021] [Indexed: 02/07/2023] Open
Abstract
Considering the lack of a comprehensive, multi-faceted overview of the ketogenic diet (KD) in relation to health issues, we compiled the evidence related to the use of the ketogenic diet in relation to its impact on the microbiome, the epigenome, diabetes, weight loss, cardiovascular health, and cancer. The KD diet could potentially increase genetic diversity of the microbiome and increase the ratio of Bacteroidetes to Firmicutes. The epigenome might be positively affected by the KD since it creates a signaling molecule known as β-hydroxybutyrate (BHB). KD has helped patients with diabetes reduce their HbA1c and reduce the need for insulin. There is evidence to suggest that a KD can help with weight loss, visceral adiposity, and appetite control. The evidence also suggests that eating a high-fat diet improves lipid profiles by lowering low-density lipoprotein (LDL), increasing high-density lipoprotein (HDL), and lowering triglycerides (TG). Due to the Warburg effect, the KD is used as an adjuvant treatment to starve cancer cells, making them more vulnerable to chemotherapy and radiation. The potential positive impacts of a KD on each of these areas warrant further analysis, improved studies, and well-designed randomized controlled trials to further illuminate the therapeutic possibilities provided by this dietary intervention.
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29
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Kobayashi S, Phung HT, Tayama S, Kagawa Y, Miyazaki H, Yamamoto Y, Maruyama T, Ishii N, Owada Y. Fatty acid-binding protein 3 regulates differentiation of IgM-producing plasma cells. FEBS J 2021; 288:1130-1141. [PMID: 32578350 DOI: 10.1111/febs.15460] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/26/2020] [Accepted: 06/09/2020] [Indexed: 01/02/2023]
Abstract
Plasma cells (PCs), which aim to protect host health, produce various subsets of immunoglobulin (Ig) in response to extracellular pathogens. Blimp-1 (encoded by Prdm1)-a protein that is highly expressed by PCs-is important for PC functions, including the generation of Igs. Fatty acid-binding protein 3 (FABP3) is a carrier protein of polyunsaturated fatty acids (PUFAs) and participates in multiple cellular functions. Although the functions of FABP3 in neurons and cardiac myocytes are well-noted, their roles in immune cells remain to be fully elucidated. In this study, we demonstrate that FABP3 is expressed in activated B cells and that FABP3 promotes PC development and IgM secretion. Moreover, we provide the first evidence that FABP3 is necessary for Blimp-1 expression, by regulating the histone modification of its promoter region. Taken together, our findings reveal that FABP3 acts as a positive regulator of B-cell activation by controlling histone acetylation of the Blimp-1 gene, thereby playing a role in host defense against pathogens.
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Affiliation(s)
- Shuhei Kobayashi
- Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hai The Phung
- Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Shunichi Tayama
- Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yoshiteru Kagawa
- Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hirofumi Miyazaki
- Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yui Yamamoto
- Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takashi Maruyama
- Mucosal Immunology Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
| | - Naoto Ishii
- Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yuji Owada
- Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan
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30
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Bellavia D, Dimarco E, Costa V, Carina V, De Luca A, Raimondi L, Fini M, Gentile C, Caradonna F, Giavaresi G. Flavonoids in Bone Erosive Diseases: Perspectives in Osteoporosis Treatment. Trends Endocrinol Metab 2021; 32:76-94. [PMID: 33288387 DOI: 10.1016/j.tem.2020.11.007] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 10/26/2020] [Accepted: 11/10/2020] [Indexed: 01/04/2023]
Abstract
Imbalance of bone homeostasis, with excessive bone resorption compared with bone formation, leads to the development of progressive osteopenia leading to lower bone resistance to load, with consequent pain and functional limitations. Phytochemicals with therapeutic and preventive effects against bone resorption have recently received increasing attention since they are potentially more suitable for long-term use than traditional therapeutic chemical compounds. In this systematic review of the literature of the past 5 years, comprehensive information is provided on flavonoids with potential antiresorption and pro-osteogenic effects. It aims to highlight the molecular mechanisms of these molecules, often epigenetic, and their possible pharmacological use, which is of great importance for the prevention and treatment of osteoporosis (OP).
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Affiliation(s)
- Daniele Bellavia
- IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche - SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, Bologna, Italy.
| | - Eufrosina Dimarco
- University of Palermo, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Section of Cellular Biology, Palermo, Italy
| | - Viviana Costa
- IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche - SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, Bologna, Italy
| | - Valeria Carina
- IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche - SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, Bologna, Italy
| | - Angela De Luca
- IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche - SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, Bologna, Italy
| | - Lavinia Raimondi
- IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche - SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, Bologna, Italy
| | - Milena Fini
- IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche - SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, Bologna, Italy
| | - Carla Gentile
- University of Palermo, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Section of Cellular Biology, Palermo, Italy
| | - Fabio Caradonna
- University of Palermo, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Section of Cellular Biology, Palermo, Italy
| | - Gianluca Giavaresi
- IRCCS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche - SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, Bologna, Italy
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Barański M, Średnicka-Tober D, Rempelos L, Hasanaliyeva G, Gromadzka-Ostrowska J, Skwarło-Sońta K, Królikowski T, Rembiałkowska E, Hajslova J, Schulzova V, Cakmak I, Ozturk L, Hallmann E, Seal C, Iversen PO, Vigar V, Leifert C. Feed Composition Differences Resulting from Organic and Conventional Farming Practices Affect Physiological Parameters in Wistar Rats-Results from a Factorial, Two-Generation Dietary Intervention Trial. Nutrients 2021; 13:377. [PMID: 33530419 PMCID: PMC7911726 DOI: 10.3390/nu13020377] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 01/15/2021] [Accepted: 01/21/2021] [Indexed: 12/18/2022] Open
Abstract
Recent human cohort studies reported positive associations between organic food consumption and a lower incidence of obesity, cancer, and several other diseases. However, there are very few animal and human dietary intervention studies that provide supporting evidence or a mechanistic understanding of these associations. Here we report results from a two-generation, dietary intervention study with male Wistar rats to identify the effects of feeds made from organic and conventional crops on growth, hormonal, and immune system parameters that are known to affect the risk of a number of chronic, non-communicable diseases in animals and humans. A 2 × 2 factorial design was used to separate the effects of contrasting crop protection methods (use or non-use of synthetic chemical pesticides) and fertilizers (mineral nitrogen, phosphorus and potassium (NPK) fertilizers vs. manure use) applied in conventional and organic crop production. Conventional, pesticide-based crop protection resulted in significantly lower fiber, polyphenol, flavonoid, and lutein, but higher lipid, aldicarb, and diquat concentrations in animal feeds. Conventional, mineral NPK-based fertilization resulted in significantly lower polyphenol, but higher cadmium and protein concentrations in feeds. Feed composition differences resulting from the use of pesticides and/or mineral NPK-fertilizer had a significant effect on feed intake, weight gain, plasma hormone, and immunoglobulin concentrations, and lymphocyte proliferation in both generations of rats and in the second generation also on the body weight at weaning. Results suggest that relatively small changes in dietary intakes of (a) protein, lipids, and fiber, (b) toxic and/or endocrine-disrupting pesticides and metals, and (c) polyphenols and other antioxidants (resulting from pesticide and/or mineral NPK-fertilizer use) had complex and often interactive effects on endocrine, immune systems and growth parameters in rats. However, the physiological responses to contrasting feed composition/intake profiles differed substantially between the first and second generations of rats. This may indicate epigenetic programming and/or the generation of "adaptive" phenotypes and should be investigated further.
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Affiliation(s)
- Marcin Barański
- Department of Animal Physiology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland
- Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland
- Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776 Warsaw, Poland
- Nafferton Ecological Farming Group, Food and Rural Development, School of Agriculture, Newcastle University, Newcastle upon Tyne, Tyne and Wear NE1 7RU, UK
| | - Dominika Średnicka-Tober
- Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776 Warsaw, Poland
- Nafferton Ecological Farming Group, Food and Rural Development, School of Agriculture, Newcastle University, Newcastle upon Tyne, Tyne and Wear NE1 7RU, UK
| | - Leonidas Rempelos
- Nafferton Ecological Farming Group, Food and Rural Development, School of Agriculture, Newcastle University, Newcastle upon Tyne, Tyne and Wear NE1 7RU, UK
| | - Gultakin Hasanaliyeva
- Nafferton Ecological Farming Group, Food and Rural Development, School of Agriculture, Newcastle University, Newcastle upon Tyne, Tyne and Wear NE1 7RU, UK
- Department of Sustainable Crop and Food Protection, Food and Environmental Sciences, Faculty of Agriculture, Universita Catollica del Sacro Cuore, I-29122 Piacenza, Italy
| | - Joanna Gromadzka-Ostrowska
- Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776 Warsaw, Poland
| | - Krystyna Skwarło-Sońta
- Department of Animal Physiology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland
| | - Tomasz Królikowski
- Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776 Warsaw, Poland
| | - Ewa Rembiałkowska
- Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776 Warsaw, Poland
| | - Jana Hajslova
- Department of Food Analysis and Nutrition, Institute of Chemical Technology, UCT Prague, 166 28 Prague, Czech Republic
| | - Vera Schulzova
- Department of Food Analysis and Nutrition, Institute of Chemical Technology, UCT Prague, 166 28 Prague, Czech Republic
| | - Ismail Cakmak
- Faculty of Engineering and Natural Sciences, Sabanci University, 34956 Istanbul, Turkey
| | - Levent Ozturk
- Faculty of Engineering and Natural Sciences, Sabanci University, 34956 Istanbul, Turkey
| | - Ewelina Hallmann
- Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776 Warsaw, Poland
| | - Chris Seal
- Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle upon Tyne NE2 4HH, UK
| | - Per Ole Iversen
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway
- Department of Haematology, Oslo University Hospital, 0424 Oslo, Norway
| | - Vanessa Vigar
- NatMed, Southern Cross University, Military Rd., Lismore, NSW 2480, Australia
| | - Carlo Leifert
- Nafferton Ecological Farming Group, Food and Rural Development, School of Agriculture, Newcastle University, Newcastle upon Tyne, Tyne and Wear NE1 7RU, UK
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway
- SCU Plant Science, Southern Cross University, Military Rd., Lismore, NSW 2480, Australia
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32
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Fatty acid-binding protein 5 limits ILC2-mediated allergic lung inflammation in a murine asthma model. Sci Rep 2020; 10:16617. [PMID: 33024217 PMCID: PMC7538993 DOI: 10.1038/s41598-020-73935-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Accepted: 09/09/2020] [Indexed: 12/24/2022] Open
Abstract
Dietary obesity is regarded as a problem worldwide, and it has been revealed the strong linkage between obesity and allergic inflammation. Fatty acid-binding protein 5 (FABP5) is expressed in lung cells, such as alveolar epithelial cells (ECs) and alveolar macrophages, and plays an important role in infectious lung inflammation. However, we do not know precise mechanisms on how lipid metabolic change in the lung affects allergic lung inflammation. In this study, we showed that Fabp5−/− mice exhibited a severe symptom of allergic lung inflammation. We sought to examine the role of FABP5 in the allergic lung inflammation and demonstrated that the expression of FABP5 acts as a novel positive regulator of ST2 expression in alveolar ECs to generate retinoic acid (RA) and supports the synthesis of RA from type II alveolar ECs to suppress excessive activation of innate lymphoid cell (ILC) 2 during allergic lung inflammation. Furthermore, high-fat diet (HFD)-fed mice exhibit the downregulation of FABP5 and ST2 expression in the lung tissue compared with normal diet (ND)-fed mice. These phenomena might be the reason why obese people are more susceptible to allergic lung inflammation. Thus, FABP5 is potentially a therapeutic target for treating ILC2-mediated allergic lung inflammation.
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33
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Al Theyab A, Almutairi T, Al-Suwaidi AM, Bendriss G, McVeigh C, Chaari A. Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes. Front Nutr 2020; 7:563605. [PMID: 33072796 PMCID: PMC7541812 DOI: 10.3389/fnut.2020.563605] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 08/26/2020] [Indexed: 12/12/2022] Open
Abstract
Type 1 diabetes (T1D) has increased over the past half century and has now become the second most frequent autoimmune disease in childhood and one of major public health concern worldwide. Evidence suggests that modern lifestyles and rapid environmental changes are driving factors that underlie this increase. The integration of these two factors brings about changes in food intake. This, in turn, alters epigenetic regulations of the genome and intestinal microbiota composition, which may ultimately play a role in pathogenesis of T1D. Recent evidence shows that dysbiosis of the gut microbiota is closely associated with T1D and that a dietary intervention can influence epigenetic changes associated with this disease and may modify gene expression patterns through epigenetic mechanisms. In this review focus on how a diet can shape the gut microbiome, its effect on the epigenome in T1D, and the future of T1D management by microbiome therapy.
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Affiliation(s)
| | | | | | | | | | - Ali Chaari
- Premedical Division, Weill Cornell Medicine Qatar, Doha, Qatar
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34
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Peiffer DS. Modulation of the host microbiome by black raspberries or their components and the therapeutic implications in cancer. FOOD FRONTIERS 2020. [DOI: 10.1002/fft2.40] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Daniel S Peiffer
- Health Sciences Division Loyola University Chicago Maywood Illinois
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35
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Topart C, Werner E, Arimondo PB. Wandering along the epigenetic timeline. Clin Epigenetics 2020; 12:97. [PMID: 32616071 PMCID: PMC7330981 DOI: 10.1186/s13148-020-00893-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 06/23/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Increasing life expectancy but also healthspan seems inaccessible as of yet but it may become a reality in the foreseeable future. To extend lifespan, it is essential to unveil molecular mechanisms involved in ageing. As for healthspan, a better understanding of the mechanisms involved in age-related pathologies is crucial. MAIN BODY We focus on the epigenetic side of ageing as ageing is traced by specific epigenetic patterns and can be measured by epigenetic clocks. We discuss to what extent exposure to environmental factor, such as alcohol use, unhealthy diet, tobacco and stress, promotes age-related conditions. We focused on inflammation, cancer and Alzheimer's disease. Finally, we discuss strategies to reverse time based on epigenetic reprogramming. CONCLUSIONS Reversibility of the epigenetic marks makes them promising targets for rejuvenation. For this purpose, a better understanding of the epigenetic mechanisms underlying ageing is essential. Epigenetic clocks were successfully designed to monitor these mechanisms and the influence of environmental factors. Further studies on age-related diseases should be conducted to determine their epigenetic signature, but also to pinpoint the defect in the epigenetic machinery and thereby identify potential therapeutic targets. As for rejuvenation, epigenetic reprogramming is still at an early stage.
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Affiliation(s)
- Clémence Topart
- Department of Chemistry, Ecole Normale Supérieure, 24 rue Lhomond, 75005, Paris, France
- PSL Research University, 60 Rue Mazarine, 75006, Paris, France
| | - Emilie Werner
- Department of Chemistry, Ecole Normale Supérieure, 24 rue Lhomond, 75005, Paris, France
- PSL Research University, 60 Rue Mazarine, 75006, Paris, France
| | - Paola B Arimondo
- EpiCBio, Epigenetic Chemical Biology, Department Structural Biology and Chemistry, Institut Pasteur, CNRS UMR n°3523, 28 rue du Dr Roux, 75015, Paris, France.
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36
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Derome N, Filteau M. A continuously changing selective context on microbial communities associated with fish, from egg to fork. Evol Appl 2020; 13:1298-1319. [PMID: 32684960 PMCID: PMC7359827 DOI: 10.1111/eva.13027] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 05/13/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
Fast increase of fish aquaculture production to meet consumer demands is accompanied by important ecological concerns such as disease outbreaks. Meanwhile, food waste is an important concern with fish products since they are highly perishable. Recent aquaculture and fish product microbiology, and more recently, microbiota research, paved the way to a highly integrated approach to understand complex relationships between host fish, product and their associated microbial communities at health/disease and preservation/spoilage frontiers. Microbial manipulation strategies are increasingly validated as promising tools either to replace or to complement traditional veterinary and preservation methods. In this review, we consider evolutionary forces driving fish microbiota assembly, in particular the changes in the selective context along the production chain. We summarize the current knowledge concerning factors governing assembly and dynamics of fish hosts and food microbial communities. Then, we discuss the current microbial community manipulation strategies from an evolutionary standpoint to provide a perspective on the potential for risks, conflict and opportunities. Finally, we conclude that to harness evolutionary forces in the development of sustainable microbiota manipulation applications in the fish industry, an integrated knowledge of the controlling abiotic and especially biotic factors is required.
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Affiliation(s)
- Nicolas Derome
- Institut de Biologie Intégrative et des Systèmes (IBIS)Université LavalQuébecQCCanada
- Département de BiologieUniversité LavalQuébecQCCanada
| | - Marie Filteau
- Département de BiologieUniversité LavalQuébecQCCanada
- Département des Sciences des alimentsInstitut sur la nutrition et les aliments fonctionnels (INAF)Université LavalQuébecQCCanada
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37
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Obri A, Serra D, Herrero L, Mera P. The role of epigenetics in the development of obesity. Biochem Pharmacol 2020; 177:113973. [DOI: 10.1016/j.bcp.2020.113973] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 04/08/2020] [Indexed: 12/13/2022]
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38
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Kujawska M, Jodynis-Liebert J. Potential of the ellagic acid-derived gut microbiota metabolite - Urolithin A in gastrointestinal protection. World J Gastroenterol 2020; 26:3170-3181. [PMID: 32684733 PMCID: PMC7336321 DOI: 10.3748/wjg.v26.i23.3170] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 05/19/2020] [Accepted: 05/23/2020] [Indexed: 02/06/2023] Open
Abstract
Urolithin A (UA) is a metabolic compound generated during the biotransformation of ellagitannins by the intestinal bacteria. The physiologically relevant micromolar concentrations of UA, achieved in the plasma and gastrointestinal tract (GI) after consumption of its dietary precursors, have been revealed to offer GI protection. The health benefit has been demonstrated to be principally related to anticancer and anti-inflammatory effects. UA has been shown to possess the capability to regulate multiple tumor and inflammatory signaling pathways and to modulate enzyme activity, including those involved in carcinogen biotransformation and antioxidant defense. The purpose of this review is to gather evidence from both in vitro and in vivo studies showing the potential of UA in GI protection alongside suggested mechanisms by which UA can protect against cancer and inflammatory diseases of the digestive tract. The data presented herein, covering both studies on the pure compound and in vivo generated UA form its natural precursor, support the potential of this metabolite in treatment interventions against GI ailments.
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Affiliation(s)
- Małgorzata Kujawska
- Department of Toxicology, Poznan University of Medical Sciences, Poznan 60631, Poland
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39
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Interactions of dietary fat with the gut microbiota: Evaluation of mechanisms and metabolic consequences. Clin Nutr 2020; 39:994-1018. [DOI: 10.1016/j.clnu.2019.05.003] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 04/25/2019] [Accepted: 05/01/2019] [Indexed: 12/12/2022]
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40
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D’Aquila P, Lynn Carelli L, De Rango F, Passarino G, Bellizzi D. Gut Microbiota as Important Mediator Between Diet and DNA Methylation and Histone Modifications in the Host. Nutrients 2020; 12:E597. [PMID: 32106534 PMCID: PMC7146473 DOI: 10.3390/nu12030597] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 02/21/2020] [Accepted: 02/21/2020] [Indexed: 12/14/2022] Open
Abstract
The human gut microbiota is a complex ecosystem consisting of trillions of microorganisms that inhabit symbiotically on and in the human intestine. They carry out, through the production of a series of metabolites, many important metabolic functions that complement the activity of mammalian enzymes and play an essential role in host digestion. Interindividual variability of microbiota structure, and consequently of the expression of its genes (microbiome), was largely ascribed to the nutritional regime. Diet influences microbiota composition and function with short- and long-term effects. In spite of the vast literature, molecular mechanisms underlying these effects still remain elusive. In this review, we summarized the current evidence on the role exerted by gut microbiota and, more specifically, by its metabolites in the establishment of the host epigenome. The interest in this topic stems from the fact that, by modulating DNA methylation and histone modifications, the gut microbiota does affect the cell activities of the hosting organism.
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Affiliation(s)
- Patrizia D’Aquila
- Department of Biology, Ecology and Earth Sciences (DIBEST), University of Calabria, 87036 Rende, Italy; (F.D.R.); (G.P.); (D.B.)
| | | | - Francesco De Rango
- Department of Biology, Ecology and Earth Sciences (DIBEST), University of Calabria, 87036 Rende, Italy; (F.D.R.); (G.P.); (D.B.)
| | - Giuseppe Passarino
- Department of Biology, Ecology and Earth Sciences (DIBEST), University of Calabria, 87036 Rende, Italy; (F.D.R.); (G.P.); (D.B.)
| | - Dina Bellizzi
- Department of Biology, Ecology and Earth Sciences (DIBEST), University of Calabria, 87036 Rende, Italy; (F.D.R.); (G.P.); (D.B.)
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41
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Neri-Numa IA, Pastore GM. Novel insights into prebiotic properties on human health: A review. Food Res Int 2020; 131:108973. [PMID: 32247494 DOI: 10.1016/j.foodres.2019.108973] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 10/05/2019] [Accepted: 12/30/2019] [Indexed: 02/07/2023]
Abstract
Dietary prebiotics can be metabolized by different colonic microorganisms and release several classes of metabolites, particularly SCFAs into the intestine lumen, influencing the host physiology. Thus, human microbiota has been the focus of one of the most dynamic research fields of our time and their efforts are directed to understand how prebiotics structures and the microbiota-derived metabolites acts on signaling cell pathways and epigenetic control. Therefore, the aim of this review is to provide an overview about the new concept of prebiotics and their mechanistic local and systemically insights related to the host health.
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Affiliation(s)
| | - Glaucia Maria Pastore
- Department of Food Science, Faculty of Food Engineering, University of Campinas, Brazil
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42
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Wu Y, Cheng Z, Bai Y, Ma X. Epigenetic Mechanisms of Maternal Dietary Protein and Amino Acids Affecting Growth and Development of Offspring. Curr Protein Pept Sci 2019; 20:727-735. [PMID: 30678627 DOI: 10.2174/1389203720666190125110150] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 12/30/2018] [Accepted: 01/10/2019] [Indexed: 12/16/2022]
Abstract
Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring's later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body's one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.
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Affiliation(s)
- Yi Wu
- State Key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Zhibin Cheng
- College of Animal Science and Technology, Yunnan Agricultural University, Kunming, Yunan 650201, China
| | - Yueyu Bai
- State Key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.,Animal Health Supervision of Henan province, Breeding Animal Genetic Performance Measurement Center of Henan Province, Zhengzhou, Henan 450008, China.,Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Xi Ma
- State Key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.,Department of Internal Medicine, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75230, United States
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43
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Sabit H, Cevik E, Tombuloglu H. Colorectal cancer: The epigenetic role of microbiome. World J Clin Cases 2019; 7:3683-3697. [PMID: 31799293 PMCID: PMC6887622 DOI: 10.12998/wjcc.v7.i22.3683] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 10/23/2019] [Accepted: 10/30/2019] [Indexed: 02/05/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer in men (746000 cases per year) and the second most common cancer in women globally (614000 cases per year). The incidence rate of CRC in developed countries (737000 cases per year) is higher than that in less developed countries (624000 cases per year). CRC can arise from genetic causes such as chromosomal instability and microsatellite instability. Several etiologic factors underlie CRC including age, diet, and lifestyle. Gut microbiota represent a proven cause of the disease, where they play pivotal roles in modulating and reshaping the host epigenome. Several active microbial metabolites have been found to drive carcinogenesis, invasion, and metastasis via modifying both the methylation landscape along with histone structure in intestinal cells. Gut microbiota, in response to diet, can exert both beneficial and harmful functions in humans, according to the intestinal balance of number and types of these bacteria. Although the intestinal microbial community is diverse among individuals, these microbes cumulatively produce 100-fold more proteins than the human genome itself, which calls for further studies to elaborate on the complicated interaction between these microorganisms and intestinal cells. Therefore, understanding the exact role that gut microbiota play in inducing CRC will help attain reliable strategies to precisely diagnose and treat this fatal disease.
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Affiliation(s)
- Hussein Sabit
- Department of Genetics, Institute for Medical Research and Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Emre Cevik
- Department of Genetics, Institute for Medical Research and Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Huseyin Tombuloglu
- Department of Genetics, Institute for Medical Research and Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
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44
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Cooperative and Escaping Mechanisms between Circulating Tumor Cells and Blood Constituents. Cells 2019; 8:cells8111382. [PMID: 31684193 PMCID: PMC6912439 DOI: 10.3390/cells8111382] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 10/29/2019] [Accepted: 11/01/2019] [Indexed: 12/21/2022] Open
Abstract
Metastasis is the leading cause of cancer-related deaths and despite measurable progress in the field, underlying mechanisms are still not fully understood. Circulating tumor cells (CTCs) disseminate within the bloodstream, where most of them die due to the attack of the immune system. On the other hand, recent evidence shows active interactions between CTCs and platelets, myeloid cells, macrophages, neutrophils, and other hematopoietic cells that secrete immunosuppressive cytokines, which aid CTCs to evade the immune system and enable metastasis. Platelets, for instance, regulate inflammation, recruit neutrophils, and cause fibrin clots, which may protect CTCs from the attack of Natural Killer cells or macrophages and facilitate extravasation. Recently, a correlation between the commensal microbiota and the inflammatory/immune tone of the organism has been stablished. Thus, the microbiota may affect the development of cancer-promoting conditions. Furthermore, CTCs may suffer phenotypic changes, as those caused by the epithelial–mesenchymal transition, that also contribute to the immune escape and resistance to immunotherapy. In this review, we discuss the findings regarding the collaborative biological events among CTCs, immune cells, and microbiome associated to immune escape and metastatic progression.
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45
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Kim KB, Lee S, Kim JH. Neuroprotective effects of urolithin A on H 2O 2-induced oxidative stress-mediated apoptosis in SK-N-MC cells. Nutr Res Pract 2019; 14:3-11. [PMID: 32042368 PMCID: PMC6997143 DOI: 10.4162/nrp.2020.14.1.3] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 07/11/2019] [Accepted: 09/06/2019] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND/OBJECTIVES Oxidative stress causes cell damage and death, which contribute to the pathogenesis of neurodegenerative diseases. Urolithin A (UA), a gut microbial-derived metabolite of ellagitannins and ellagic acid, has high bioavailability and various health benefits such as antioxidant and anti-inflammatory effects. However, it is unknown whether it has protective effects against oxidative stress-induced cell death. We investigated whether UA ameliorates H2O2-induced neuronal cell death. MATERIALS/METHODS We induced oxidative damage with 300 µM H2O2 after UA pretreatment at concentrations of 1.25, 2.5, and 5 µM in SK-N-MC cells. Cytotoxicity and cell viability were determined using the CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using a 2,7-dichlorofluorescein diacetate assay. Hoechst 33342 staining was used to characterize morphological changes in apoptotic cells. The expressions of apoptosis proteins were measured using Western blotting. RESULTS UA significantly increased cell viability and decreased intracellular ROS production in a dose-dependent manner in SK-N-MC cells. It also decreased the Bax/Bcl-2 ratio and the expressions of cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved PARP. In addition, it suppressed the phosphorylation of the p38 mitogen-activated protein kinase (MAPK) pathway. CONCLUSIONS UA attenuates oxidative stress-induced apoptosis via inhibiting the mitochondrial-related apoptosis pathway and modulating the p38 MAPK pathway, suggesting that it may be an effective neuroprotective agent.
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Affiliation(s)
- Kkot Byeol Kim
- Research Institute, Seoul Medical Center, Seoul 02053, Korea
| | - Seonah Lee
- Research Institute, Seoul Medical Center, Seoul 02053, Korea
| | - Jung Hee Kim
- Research Institute, Seoul Medical Center, Seoul 02053, Korea.,Department of Neurosurgery, Seoul Medical Center, 156 Shinnea-ro, Seoul 02053, Korea
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Lee HS. The interaction between gut microbiome and nutrients on development of human disease through epigenetic mechanisms. Genomics Inform 2019; 17:e24. [PMID: 31610620 PMCID: PMC6808642 DOI: 10.5808/gi.2019.17.3.e24] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 09/22/2019] [Indexed: 02/06/2023] Open
Abstract
Early environmental exposure is recognized as a key factor for long-term health based on the Developmental Origins of Health and Disease hypothesis. It considers that early-life nutrition is now being recognized as a major contributor that may permanently program change of organ structure and function toward the development of diseases, in which epigenetic mechanisms are involved. Recent researches indicate early-life environmental factors modulate the microbiome development and the microbiome might be mediate diet-epigenetic interaction. This review aims to define which nutrients involve microbiome development during the critical window of susceptibility to disease, and how microbiome modulation regulates epigenetic changes and influences human health and future prevention strategies.
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Affiliation(s)
- Ho-Sun Lee
- Forensic Toxicology Division, Daegu Institute, National Forensic Service, Chilgok 39872, Korea
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47
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Martínez-Cano J, Campos-Sánchez E, Cobaleda C. Epigenetic Priming in Immunodeficiencies. Front Cell Dev Biol 2019; 7:125. [PMID: 31355198 PMCID: PMC6635466 DOI: 10.3389/fcell.2019.00125] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 06/26/2019] [Indexed: 12/17/2022] Open
Abstract
Immunodeficiencies (IDs) are disorders of the immune system that increase susceptibility to infections and cancer, and are therefore associated with elevated morbidity and mortality. IDs can be primary (not caused by other condition or exposure) or secondary due to the exposure to different agents (infections, chemicals, aging, etc.). Most primary immunodeficiencies (PIDs) are of genetic origin, caused by mutations affecting genes with key roles in the development or function of the cells of the immune system. A large percentage of PIDs are associated with a defective development and/or function of lymphocytes and, especially, B cells, the ones in charge of generating the different types of antibodies. B-cell development is a tightly regulated process in which many different factors participate. Among the regulators of B-cell differentiation, a correct epigenetic control of cellular identity is essential for normal cell function. With the advent of next-generation sequencing (NGS) techniques, more and more alterations in different types of epigenetic regulators are being described at the root of PIDs, both in humans and in animal models. At the same time, it is becoming increasingly clear that epigenetic alterations triggered by the exposure to environmental agents have a key role in the development of secondary immunodeficiencies (SIDs). Due to their largely reversible nature, epigenetic modifications are quickly becoming key therapeutic targets in other diseases where their contribution has been known for more time, like cancer. Here, we establish a parallelism between IDs and the nowadays accepted role of epigenetics in cancer initiation and progression, and propose that epigenetics forms a "third axis" (together with genetics and external agents) to be considered in the etiology of IDs, and linking PIDs and SIDs at the molecular level. We therefore postulate that IDs arise due to a variable contribution of (i) genetic, (ii) environmental, and (iii) epigenetic causes, which in fact form a continuum landscape of all possible combinations of these factors. Additionally, this implies the possibility of a fully epigenetically triggered mechanism for some IDs. This concept would have important prophylactic and translational implications, and would also imply a more blurred frontier between primary and secondary immunodeficiencies.
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Affiliation(s)
| | | | - César Cobaleda
- Department of Cell Biology and Immunology, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas –Universidad Autónoma de Madrid), Madrid, Spain
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48
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Murgier J, Everaerts C, Farine JP, Ferveur JF. Live yeast in juvenile diet induces species-specific effects on Drosophila adult behaviour and fitness. Sci Rep 2019; 9:8873. [PMID: 31222019 PMCID: PMC6586853 DOI: 10.1038/s41598-019-45140-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Accepted: 05/24/2019] [Indexed: 02/07/2023] Open
Abstract
The presence and the amount of specific yeasts in the diet of saprophagous insects such as Drosophila can affect their development and fitness. However, the impact of different yeast species in the juvenile diet has rarely been investigated. Here, we measured the behavioural and fitness effects of three live yeasts (Saccharomyces cerevisiae = SC; Hanseniaspora uvarum = HU; Metschnikowia pulcherrima = MP) added to the diet of Drosophila melanogaster larvae. Beside these live yeast species naturally found in natural Drosophila populations or in their food sources, we tested the inactivated "drySC" yeast widely used in Drosophila research laboratories. All flies were transferred to drySC medium immediately after adult emergence, and several life traits and behaviours were measured. These four yeast diets had different effects on pre-imaginal development: HU-rich diet tended to shorten the "egg-to-pupa" period of development while MP-rich diet induced higher larval lethality compared to other diets. Pre- and postzygotic reproduction-related characters (copulatory ability, fecundity, cuticular pheromones) varied according to juvenile diet and sex. Juvenile diet also changed adult food choice preference and longevity. These results indicate that specific yeast species present in natural food sources and ingested by larvae can affect their adult characters crucial for fitness.
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Affiliation(s)
- Juliette Murgier
- Université de Bourgogne Franche-Comté, Centre des Sciences du Goût et de l'Alimentation, AgroSup-UMR 6265 CNRS, UMR 1324 INRA, 6, Bd Gabriel, F-21000, Dijon, France
| | - Claude Everaerts
- Université de Bourgogne Franche-Comté, Centre des Sciences du Goût et de l'Alimentation, AgroSup-UMR 6265 CNRS, UMR 1324 INRA, 6, Bd Gabriel, F-21000, Dijon, France
| | - Jean-Pierre Farine
- Université de Bourgogne Franche-Comté, Centre des Sciences du Goût et de l'Alimentation, AgroSup-UMR 6265 CNRS, UMR 1324 INRA, 6, Bd Gabriel, F-21000, Dijon, France
| | - Jean-François Ferveur
- Université de Bourgogne Franche-Comté, Centre des Sciences du Goût et de l'Alimentation, AgroSup-UMR 6265 CNRS, UMR 1324 INRA, 6, Bd Gabriel, F-21000, Dijon, France.
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Jaskiw GE, Obrenovich ME, Donskey CJ. The phenolic interactome and gut microbiota: opportunities and challenges in developing applications for schizophrenia and autism. Psychopharmacology (Berl) 2019; 236:1471-1489. [PMID: 31197432 DOI: 10.1007/s00213-019-05267-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 05/01/2019] [Indexed: 12/14/2022]
Abstract
Schizophrenia and autism spectrum disorder have long been associated with elevated levels of various small phenolic molecules (SPMs). In turn, the gut microbiota (GMB) has been implicated in the kinetics of many of these analytes. Unfortunately, research into the possible relevance of GMB-mediated SPMs to neuropsychiatry continues to be limited by heterogeneous study design, numerous sources of variance and technical challenges. Some SPMs have multiple structural isomers and most have conjugates. Without specialized approaches, SPMs can be incorrectly assigned or inaccurately quantified. In addition, SPM levels can be affected by dietary polyphenol or protein consumption and by various medications and diseases. Nonetheless, heterotypical excretion of various SPMs in association with schizophrenia or autism continues to be reported in independent samples. Recent studies in human cerebrospinal fluid demonstrate the presence of many SPMs A large number of these are bioactive in experimental models. Whether such mechanisms are relevant to the human brain in health or disease is not known. Systematic metabolomic and microbiome studies of well-characterized populations, an appreciation of multiple confounds, and implementation of standardized approaches across platforms and sites are needed to delineate the potential utility of the phenolic interactome in neuropsychiatry.
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Affiliation(s)
- George E Jaskiw
- Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA. .,School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
| | - Mark E Obrenovich
- Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA.,Department of Chemistry, Case Western Reserve University, Cleveland, OH, USA.,Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, USA.,Department of Chemistry, Cleveland State University, Cleveland, OH, USA
| | - Curtis J Donskey
- Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA.,School of Medicine, Case Western Reserve University, Cleveland, OH, USA
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50
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Ganesan A. Epigenetics: the first 25 centuries. Philos Trans R Soc Lond B Biol Sci 2019; 373:rstb.2017.0067. [PMID: 29685971 DOI: 10.1098/rstb.2017.0067] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/01/2018] [Indexed: 02/06/2023] Open
Abstract
Epigenetics is a natural progression of genetics as it aims to understand how genes and other heritable elements are regulated in eukaryotic organisms. The history of epigenetics is briefly reviewed, together with the key issues in the field today. This themed issue brings together a diverse collection of interdisciplinary reviews and research articles that showcase the tremendous recent advances in epigenetic chemical biology and translational research into epigenetic drug discovery.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.
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Affiliation(s)
- A Ganesan
- School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK .,Freiburg Institute of Advanced Studies (FRIAS), University of Freiburg, 79104 Freiburg im Breisgau, Germany
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