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Amir S, Kumar M, Kumar V, Mohanty D. HgutMgene-Miner: In silico genome mining tool for deciphering the drug-metabolizing potential of human gut microbiome. Comput Biol Med 2025; 186:109679. [PMID: 39862468 DOI: 10.1016/j.compbiomed.2025.109679] [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: 08/23/2024] [Revised: 01/05/2025] [Accepted: 01/12/2025] [Indexed: 01/27/2025]
Abstract
The biotransformation of drugs by enzymes from the human microbiome can produce active or inactive products, impacting the bioactivity and function of these drugs inside the human host. However, understanding the biotransformation reactions of drug molecules catalyzed by bacterial enzymes in human microbiota is still limited. Hence, to characterize drug utilization capabilities across all the microbial phyla inside the human gut, we have used a knowledge-based approach to develop HgutMgene-Miner software which predicts xenobiotic metabolizing enzymes (XMEs) through genome mining. HgutMgene-Miner derives its predictive power from the MicrobiomeMetDB database, which systematically catalogs all known biotransformation reactions of xenobiotics and primary metabolites mediated by host-associated microbial enzymes. Over 10,000 isolate genomes from 830 different bacterial species found in the Unified Human Gastrointestinal Genome (UHGG) collection have been analyzed by HgutMgene-Miner. This led to the identification of 89,377 xenobiotic metabolizing enzymes (XMEs) across 13 phyla, with the greatest diversity in Bacteroidota, Firmicutes_A, Firmicutes, and Proteobacteria. Bacteroides, Clostridium, and Alitsipes were found to be the richest genera, while Actinomyces were found to encode the fewest XMEs, primarily metabolizing Diclofenac, a nonsteroidal anti-inflammatory drug. Overall, we discovered XMEs in 220 genera, exceeding the number experimentally reported in fewer than 10 genera. Notably, Eggerthella lenta's cgr2 involved in Digoxin inactivation was identified in very distant Holdemania genera, likewise Clostridium leptum's nitroreductase, involved in Nitrazepam metabolism, was found in Fusobacterium. These findings highlight the extensive and diverse distribution of XMEs across microbial taxa.
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Affiliation(s)
- Sana Amir
- National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
| | - Manish Kumar
- National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
| | - Vikas Kumar
- National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
| | - Debasisa Mohanty
- National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
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Charitos IA, Scacco S, Cotoia A, Castellaneta F, Castellana G, Pasqualotto F, Venneri M, Ferrulli A, Aliani M, Santacroce L, Carone M. Intestinal Microbiota Dysbiosis Role and Bacterial Translocation as a Factor for Septic Risk. Int J Mol Sci 2025; 26:2028. [PMID: 40076650 PMCID: PMC11900423 DOI: 10.3390/ijms26052028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 02/18/2025] [Accepted: 02/22/2025] [Indexed: 03/14/2025] Open
Abstract
The human immune system is closely linked to microbiota such as a complex symbiotic relationship during the coevolution of vertebrates and microorganisms. The transfer of microorganisms from the mother's microbiota to the newborn begins before birth during gestation and is considered the initial phase of the intestinal microbiota (IM). The gut is an important site where microorganisms can establish colonies. The IM contains polymicrobial communities, which show complex interactions with diet and host immunity. The tendency towards dysbiosis of the intestinal microbiota is influenced by local but also extra-intestinal factors such as inflammatory processes, infections, or a septic state that can aggravate it. Pathogens could trigger an immune response, such as proinflammatory responses. In addition, changes in the host immune system also influence the intestinal community and structure with additional translocation of pathogenic and non-pathogenic bacteria. Finally, local intestinal inflammation has been found to be an important factor in the growth of pathogenic microorganisms, particularly in its role in sepsis. The aim of this article is to be able to detect the current knowledge of the mechanisms that can lead to dysbiosis of the intestinal microbiota and that can cause bacterial translocation with a risk of infection or septic state and vice versa.
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Affiliation(s)
- Ioannis Alexandros Charitos
- Pneumology and Respiratory Rehabilitation Unit, Istituti Clinici Scientifici Maugeri IRCCS, “Istitute” of Bari, 70124 Bari, Italy; (I.A.C.); (G.C.); (F.P.); (M.A.); (M.C.)
- Doctoral School, Applied Neurosciences, University of Bari (UNIBA), 70124 Bari, Italy
| | - Salvatore Scacco
- Dipartimento di Biomedicina Traslazionale e Neuroscienze (DiBraiN), Scuola di Medicina, Università Degli Studi di Bari, Aldo Moro, 70124 Bari, Italy;
- U.O. Medicina, Ospedale Mater Dei-CBH, 70125 Bari, Italy
| | - Antonella Cotoia
- Department of Intensive Care, University Hospital of Foggia, 71121 Foggia, Italy
| | - Francesca Castellaneta
- U.O.C. Servizio di Immunoematologia e Medicina Trasfusionale—S.I.M.T. Ospedale Di Venere, 70131 Bari, Italy;
| | - Giorgio Castellana
- Pneumology and Respiratory Rehabilitation Unit, Istituti Clinici Scientifici Maugeri IRCCS, “Istitute” of Bari, 70124 Bari, Italy; (I.A.C.); (G.C.); (F.P.); (M.A.); (M.C.)
| | - Federico Pasqualotto
- Pneumology and Respiratory Rehabilitation Unit, Istituti Clinici Scientifici Maugeri IRCCS, “Istitute” of Bari, 70124 Bari, Italy; (I.A.C.); (G.C.); (F.P.); (M.A.); (M.C.)
- Department of Public Health and Infectious Diseases, Pulmonary Division, Sapienza University of Rome, Policlinico Umberto I Hospital, Rome, Via del Policlinico 155, 00155 Rome, Italy
| | - Maria Venneri
- Genomics and Proteomics Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, “Istitute” of Bari, 70124 Bari, Italy; (M.V.); (A.F.)
| | - Angela Ferrulli
- Genomics and Proteomics Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, “Istitute” of Bari, 70124 Bari, Italy; (M.V.); (A.F.)
| | - Maria Aliani
- Pneumology and Respiratory Rehabilitation Unit, Istituti Clinici Scientifici Maugeri IRCCS, “Istitute” of Bari, 70124 Bari, Italy; (I.A.C.); (G.C.); (F.P.); (M.A.); (M.C.)
| | - Luigi Santacroce
- Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, The University of Bari, 70124 Bari, Italy;
| | - Mauro Carone
- Pneumology and Respiratory Rehabilitation Unit, Istituti Clinici Scientifici Maugeri IRCCS, “Istitute” of Bari, 70124 Bari, Italy; (I.A.C.); (G.C.); (F.P.); (M.A.); (M.C.)
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Davias A, Lyon-Caen S, Rolland M, Iszatt N, Thomsen C, Haug LS, Sakhi AK, Monot C, Rayah Y, Ilhan ZE, Jovanovic N, Philippat C, Eggesbo M, Lepage P, Slama R. Perinatal Exposure to Phenols and Poly- and Perfluoroalkyl Substances and Gut Microbiota in One-Year-Old Children. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:15395-15414. [PMID: 39173114 DOI: 10.1021/acs.est.3c09927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/24/2024]
Abstract
The role of the gut microbiota in human health calls for a better understanding of its determinants. In particular, the possible effects of chemicals with widespread exposure other than pharmaceuticals are little known. Our aim was to characterize the sensitivity of the early-life gut microbiota to specific chemicals with possible antimicrobial action. Within the SEPAGES French couple-child cohort, we assessed 12 phenols in repeated urine samples from 356 pregnant women and their offspring and 19 poly- and perfluoroalkyl substances (PFASs) in serum from the pregnant women. We collected stool samples from the children at one year of age, in which the V3-V4 region of the 16S rRNA gene was sequenced, allowing for gut bacterial profiling. Associations of each chemical with α- and β-diversity indices of the gut microbiota and with the relative abundance of the most abundant taxa were assessed using single-pollutant and mixture (BKMR) models. Perinatal exposure to certain parabens was associated with gut microbiota α- and β-diversity and with Firmicutes and Proteobacteria. Suggestive associations of certain phenols with genera of the Lachnospiraceae and Enterobacteriaceae families were observed, but these were not maintained after correction for multiple testing. Parabens, which have known antimicrobial properties, might disrupt the child gut microbiota, but larger studies are required to confirm these findings.
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Affiliation(s)
- Aline Davias
- Environmental Epidemiology Applied to Development and Respiratory Health Team, Institute for Advanced Biosciences, University Grenoble Alpes, Inserm, CNRS, La Tronche 38700, France
| | - Sarah Lyon-Caen
- Environmental Epidemiology Applied to Development and Respiratory Health Team, Institute for Advanced Biosciences, University Grenoble Alpes, Inserm, CNRS, La Tronche 38700, France
| | - Matthieu Rolland
- Environmental Epidemiology Applied to Development and Respiratory Health Team, Institute for Advanced Biosciences, University Grenoble Alpes, Inserm, CNRS, La Tronche 38700, France
| | - Nina Iszatt
- Division of Climate and Environmental Health, Norwegian Institute of Public Health (NIPH), Oslo 0213, Norway
| | - Cathrine Thomsen
- Division of Climate and Environmental Health, Norwegian Institute of Public Health (NIPH), Oslo 0213, Norway
| | - Line Småstuen Haug
- Division of Climate and Environmental Health, Norwegian Institute of Public Health (NIPH), Oslo 0213, Norway
| | - Amrit Kaur Sakhi
- Division of Climate and Environmental Health, Norwegian Institute of Public Health (NIPH), Oslo 0213, Norway
| | - Celine Monot
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas 78350, France
| | - Yamina Rayah
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas 78350, France
| | - Zehra Esra Ilhan
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas 78350, France
| | - Nicolas Jovanovic
- Environmental Epidemiology Applied to Development and Respiratory Health Team, Institute for Advanced Biosciences, University Grenoble Alpes, Inserm, CNRS, La Tronche 38700, France
| | - Claire Philippat
- Environmental Epidemiology Applied to Development and Respiratory Health Team, Institute for Advanced Biosciences, University Grenoble Alpes, Inserm, CNRS, La Tronche 38700, France
| | - Merete Eggesbo
- Division of Climate and Environmental Health, Norwegian Institute of Public Health (NIPH), Oslo 0213, Norway
| | - Patricia Lepage
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas 78350, France
| | - Rémy Slama
- Environmental Epidemiology Applied to Development and Respiratory Health Team, Institute for Advanced Biosciences, University Grenoble Alpes, Inserm, CNRS, La Tronche 38700, France
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Li Y, Ma H, Wang J. Effects of polycyclic aromatic hydrocarbons on the gut-testis axis. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 280:116539. [PMID: 38870734 DOI: 10.1016/j.ecoenv.2024.116539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/24/2024] [Accepted: 05/31/2024] [Indexed: 06/15/2024]
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds which are comprised of two or more fused benzene rings. As a typical environmental pollutant, PAHs are widely distributed in water, soil, atmosphere and food. Despite extensive researches on the mechanisms of health damage caused by PAHs, especially their carcinogenic and mutagenic toxicity, there is still a lack of comprehensive summarization and synthesis regarding the mechanisms of PAHs on the gut-testis axis, which represents an intricate interplay between the gastrointestinal and reproductive systems. Thus, this review primarily focuses on the potential forms of interaction between PAHs and the gut microbiota and summarizes their adverse outcomes that may lead to gut microbiota dysbiosis, then compiles the possible mechanistic pathways on dysbiosis of the gut microbiota impairing the male reproductive function, in order to provide valuable insights for future research and guide further exploration into the intricate mechanisms underlying the impact of gut microbiota dysbiosis caused by PAHs on male reproductive function.
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Affiliation(s)
- Yuanjie Li
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China
| | - Haitao Ma
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China
| | - Junling Wang
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China.
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Stoeltje L, Luc JK, Haddad T, Schrankel CS. The roles of ABCB1/P-glycoprotein drug transporters in regulating gut microbes and inflammation: insights from animal models, old and new. Philos Trans R Soc Lond B Biol Sci 2024; 379:20230074. [PMID: 38497255 PMCID: PMC10945405 DOI: 10.1098/rstb.2023.0074] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 02/13/2024] [Indexed: 03/19/2024] Open
Abstract
Commensal enteric bacteria have evolved systems that enable growth in the ecologic niche of the host gastrointestinal tract. Animals evolved parallel mechanisms to survive the constant exposure to bacteria and their metabolic by-products. We propose that drug transporters encompass a crucial system to managing the gut microbiome. Drug transporters are present in the apical surface of gut epithelia. They detoxify cells from small molecules and toxins (xenobiotics) in the lumen. Here, we review what is known about commensal structure in the absence of the transporter ABCB1/P-glycoprotein in mammalian models. Knockout or low-activity alleles of ABCB1 lead to dysbiosis, Crohn's disease and ulcerative colitis in mammals. However, the exact function of ABCB1 in these contexts remain unclear. We highlight emerging models-the zebrafish Danio rerio and sea urchin Lytechinus pictus-that are poised to help dissect the fundamental mechanisms of ATP-binding cassette (ABC) transporters in the tolerance of commensal and pathogenic communities in the gut. We and others hypothesize that ABCB1 plays a direct role in exporting inflammatory bacterial products from host epithelia. Interdisciplinary work in this research area will lend novel insight to the transporter-mediated pathways that impact microbiome community structure and accelerate the pathogenesis of inflammatory bowel disease when perturbed. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.
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Affiliation(s)
- Lauren Stoeltje
- Department of Biology, San Diego State University, 5500 Campanile Drive, Life Sciences North, Room 321, San Diego, CA 92182, USA
| | - Jenna K. Luc
- Department of Biology, San Diego State University, 5500 Campanile Drive, Life Sciences North, Room 321, San Diego, CA 92182, USA
| | - Timothaus Haddad
- Department of Biology, San Diego State University, 5500 Campanile Drive, Life Sciences North, Room 321, San Diego, CA 92182, USA
| | - Catherine S. Schrankel
- Department of Biology, San Diego State University, 5500 Campanile Drive, Life Sciences North, Room 321, San Diego, CA 92182, USA
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Yu J, Chen Y, Wang J, Wu H. Research progress on the relationship between traumatic brain injury and brain-gut-microbial axis. IBRAIN 2024; 10:477-487. [PMID: 39691426 PMCID: PMC11649388 DOI: 10.1002/ibra.12153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 03/12/2024] [Accepted: 03/14/2024] [Indexed: 12/19/2024]
Abstract
Traumatic brain injury (TBI) is a common disease with a high rate of death and disability, which poses a serious threat to human health; thus, the effective treatment of TBI has been a high priority. The brain-gut-microbial (BGM) axis, as a bidirectional communication network for information exchange between the brain and gut, plays a crucial role in neurological diseases. This article comprehensively explores the interrelationship between the BGM axis and TBI, including its physiological effects, basic pathophysiology, and potential therapeutic strategies. It highlights how the bidirectional regulatory pathways of the BGM axis could provide new insights into clinical TBI treatment and underscores the necessity for advanced research and development of innovative clinical treatments for TBI.
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Affiliation(s)
- Jie Yu
- Department of NeurosurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiGuizhouChina
| | - Yun‐Xin Chen
- Department of NeurosurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiGuizhouChina
| | - Jin‐Wei Wang
- Department of NeurosurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiGuizhouChina
| | - Hai‐Tao Wu
- Department of NeurosurgeryAffiliated Hospital of Zunyi Medical UniversityZunyiGuizhouChina
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Hariti M, Kamel A, Ghozlani A, Djennane N, Djenouhat K, Aksas K, Hamouli-Saïd Z. Disruption of spermatogenesis in testicular adult Wistar rats after short-term exposure to high dose of glyphosate based-herbicide: Histopathological and biochemical changes. Reprod Biol 2024; 24:100865. [PMID: 38402720 DOI: 10.1016/j.repbio.2024.100865] [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: 10/10/2023] [Revised: 01/30/2024] [Accepted: 02/12/2024] [Indexed: 02/27/2024]
Abstract
Glyphosate is an endocrine disruptor and can act on the activity of certain enzymes of metabolism subsequently altering some functions such as reproduction. The goal of the present study is to evaluate the involvement of glyphosate based-herbicide (GBH) in spermatogenesis disruption and to investigate which cells of the adult Wistar rat testis are most affected by short-term exposure to GBH. Treated groups received a diluted solution of GBH orally for 21 days (D1: 102.5 mg/Kg; D2: 200 mg/Kg; D3: 400 mg/Kg). The control group (C) received water in the same manner. Hormone levels, oxidative stress markers were evaluated, histological and morphometric analysis were performed, AR and p53 expression was conducted. Seminiferious epithelium sloughing associated to erosion of Sertoli and spermatogonia from the basement of the seminiferous tubules, with intraluminal exfoliated cells among with immature spermatids were observed. A significant change in morphometric measurement and significant decrease in AR expression in Sertoli cells were noted for all treated groups. A significant increase in NO level and p53 expression in Leydig cells were showed for animals treated with 200 and 400 mg/kg BW/day. These data demonstrate that short-term exposure to high doses of GBH has led to a disruption of certain parameters that could disturb spermatogenesis. The treatment showed that both Leydig and Sertoli cells are affected in the same manner by GBH, the activation of p53 expression in both Leydig cells and peritubular myloid cells nuclei, and the reduction in AR expression in Sertoli cells, which resulted in important testicular damage.
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Affiliation(s)
- Meriem Hariti
- L.B.P.O/Section Endocrinology, Faculty of Biological Sciences, USTHB, BP 32 El-Alia, Bab Ezzouar, 16 111 Algiers, Algeria.
| | - Assia Kamel
- L.B.P.O/Section Endocrinology, Faculty of Biological Sciences, USTHB, BP 32 El-Alia, Bab Ezzouar, 16 111 Algiers, Algeria
| | - Amel Ghozlani
- L.B.P.O/Section Endocrinology, Faculty of Biological Sciences, USTHB, BP 32 El-Alia, Bab Ezzouar, 16 111 Algiers, Algeria
| | - Nacima Djennane
- Faculty of Medicine - University of Algiers1 / Pathological Anatomy and Cytology Department, Mohammed Lamine Debaghine Hospital, Bab El Oued, Algeria
| | - Kamel Djenouhat
- Faculty of Medicine - University of Algiers1 / Central Laboratory, Public Hospital Etablishment of Rouiba, Algeria
| | - Kahina Aksas
- Faculty of Medicine - University of Algiers1 / Central Laboratory, Mohammed Lamine Debaghine Hospital, Bab El Oued, Algeria
| | - Zohra Hamouli-Saïd
- L.B.P.O/Section Endocrinology, Faculty of Biological Sciences, USTHB, BP 32 El-Alia, Bab Ezzouar, 16 111 Algiers, Algeria
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Magnuson JT, Monticelli G, Schlenk D, Bisesi JH, Pampanin DM. Connecting gut microbiome changes with fish health conditions in juvenile Atlantic cod (Gadus morhua) exposed to dispersed crude oil. ENVIRONMENTAL RESEARCH 2023; 234:116516. [PMID: 37399986 DOI: 10.1016/j.envres.2023.116516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/23/2023] [Accepted: 06/25/2023] [Indexed: 07/05/2023]
Abstract
Polycyclic aromatic hydrocarbons found in crude oil can impair fish health following sublethal exposure. However, the dysbiosis of microbial communities within the fish host and influence it has on the toxic response of fish following exposure has been less characterized, particularly in marine species. To better understand the effect of dispersed crude oil (DCO) on juvenile Atlantic cod (Gadus morhua) microbiota composition and potential targets of exposure within the gut, fish were exposed to 0.05 ppm DCO for 1, 3, 7, or 28 days and 16 S metagenomic and metatranscriptomic sequencing on the gut and RNA sequencing on intestinal content were conducted. In addition to assessing species composition, richness, and diversity from microbial gut community analysis and transcriptomic profiling, the functional capacity of the microbiome was determined. Mycoplasma and Aliivibrio were the two most abundant genera after DCO exposure and Photobacterium the most abundant genus in controls, after 28 days. Metagenomic profiles were only significantly different between treatments after a 28-day exposure. The top identified pathways were involved in energy and the biosynthesis of carbohydrates, fatty acids, amino acids, and cellular structure. Biological processes following fish transcriptomic profiling shared common pathways with microbial functional annotations such as energy, translation, amide biosynthetic process, and proteolysis. There were 58 differently expressed genes determined from metatranscriptomic profiling after 7 days of exposure. Predicted pathways that were altered included those involved in translation, signal transduction, and Wnt signaling. EIF2 signaling was consistently dysregulated following exposure to DCO, regardless of exposure duration, with impairments in IL-22 signaling and spermine and spermidine biosynthesis in fish after 28 days. Data were consistent with predictions of a potentially reduced immune response related to gastrointestinal disease. Herein, transcriptomic-level responses helped explain the relevance of differences in gut microbial communities in fish following DCO exposure.
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Affiliation(s)
- Jason T Magnuson
- Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway.
| | - Giovanna Monticelli
- Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway
| | - Daniel Schlenk
- Department of Environmental Sciences, University of California, Riverside, Riverside, CA, USA
| | - Joseph H Bisesi
- Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA
| | - Daniela M Pampanin
- Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway
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Hou R, Zhang S, Huang Q, Lin L, Li H, Li J, Liu S, Sun C, Xu X. Role of Gastrointestinal Microbiota from Crucian Carp in Microbial Transformation and Estrogenicity Modification of Novel Plastic Additives. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2023; 57:11476-11488. [PMID: 37462611 DOI: 10.1021/acs.est.3c03595] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/09/2023]
Abstract
Ingestion is a major exposure route for hydrophobic organic pollutants in fish, but the microbial transformation and estrogenic modification of the novel plastic additives by the gut microbiota of fish remain obscure. Using an in vitro approach, we provide evidence that structure-related transformation of various plastic additives by the gastric and intestinal (GI) microbiota from crucian carp, with the degradation ratio of bisphenols and triphenyl phosphate faster than those of brominated compounds. The degradation kinetics for these pollutants could be limited by oxygen and cometabolic substrates (i.e., glucose). The fish GI microbiota could utilize the vast majority of carbon sources in a Biolog EcoPlate, suggesting their high metabolic potential and ability to transform various organic compounds. Unique microorganisms associated with transformation of the plastic additives including genera of Citrobacter, Klebsiella, and some unclassified genera in Enterobacteriaceae were identified by combining high-throughput genetic analyses and metagenomic analyses. Through identification of anaerobic transformation products by high-resolution mass spectrometry, alkyl-cleavage was found the common transformation mechanism, and hydrolysis was the major pathway for ester-containing pollutants. After anaerobic incubation, the estrogenic activities of triphenyl phosphate and bisphenols A, F, and AF declined, whereas that of bisphenol AP increased.
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Affiliation(s)
- Rui Hou
- Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
| | - Siqi Zhang
- Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Qianyi Huang
- Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Lang Lin
- Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
| | - Hengxiang Li
- Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
- Sanya Institute of Ocean Eco-Environmental Engineering, Sanya 572100, China
| | - Jingxi Li
- Key Laboratory of Marine Eco-environmental Science and Technology, Marine Bioresource and Environment Research Center, First Institute of Oceanography, Ministry of Natural Resources, Qingdao, 266061, China
| | - Shan Liu
- Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
- Sanya Institute of Ocean Eco-Environmental Engineering, Sanya 572100, China
| | - Chengjun Sun
- Key Laboratory of Marine Eco-environmental Science and Technology, Marine Bioresource and Environment Research Center, First Institute of Oceanography, Ministry of Natural Resources, Qingdao, 266061, China
| | - Xiangrong Xu
- Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
- Sanya Institute of Ocean Eco-Environmental Engineering, Sanya 572100, China
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Li J, Chen X, Zhao S, Chen J. Arsenic-Containing Medicine Treatment Disturbed the Human Intestinal Microbial Flora. TOXICS 2023; 11:toxics11050458. [PMID: 37235272 DOI: 10.3390/toxics11050458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/07/2023] [Accepted: 05/09/2023] [Indexed: 05/28/2023]
Abstract
Human intestinal microbiome plays vital role in maintaining intestinal homeostasis and interacting with xenobiotics. Few investigations have been conducted to understand the effect of arsenic-containing medicine exposure on gut microbiome. Most animal experiments are onerous in terms of time and resources and not in line with the international effort to reduce animal experiments. We explored the overall microbial flora by 16S rRNA genes analysis in fecal samples from acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA). Gut microbiomes were found to be overwhelmingly dominated by Firmicutes and Bacteroidetes after taking medicines containing arsenic in APL patients. The fecal microbiota composition of APL patients after treatment showed lower diversity and uniformity shown by the alpha diversity indices of Chao, Shannon, and Simpson. Gut microbiome operational taxonomic unit (OTU) numbers were associated with arsenic in the feces. We evaluated Bifidobacterium adolescentis and Lactobacillus mucosae to be a keystone in APL patients after treatment. Bacteroides at phylum or genus taxonomic levels were consistently affected after treatment. In the most common gut bacteria Bacteroides fragilis, arsenic resistance genes were significantly induced by arsenic exposure in anaerobic pure culture experiments. Without an animal model, without taking arsenicals passively, the results evidence that arsenic exposure by drug treatment is not only associated with alterations in intestinal microbiome development at the abundance and diversity level, but also induced arsenic biotransformation genes (ABGs) at the function levels which may even extend to arsenic-related health outcomes in APL.
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Affiliation(s)
- Jiaojiao Li
- College of Ecology and Environmental Sciences & Yunnan Key Laboratory for Plateau Mountain Ecology and Restoration of Degraded Environments, Yunnan University, Kunming 650500, China
| | - Xinshuo Chen
- College of Ecology and Environmental Sciences & Yunnan Key Laboratory for Plateau Mountain Ecology and Restoration of Degraded Environments, Yunnan University, Kunming 650500, China
| | - Shixiang Zhao
- Hematology Department of First People's Hospital of Yunnan Province, Kunming 650032, China
| | - Jian Chen
- Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
- Institute of Environmental Remediation and Human Health, College of Ecology and Environment, Southwest Forestry University, Kunming 650224, China
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11
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Singh VK, Gunasekaran P, Kumari M, Krishnan D, Ramachandran VK. Animal sourced biopolymer for mitigating xenobiotics and hazardous materials. PHYSICAL SCIENCES REVIEWS 2023. [DOI: 10.1515/psr-2022-0221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2023]
Abstract
Abstract
Over the past several decades, xenobiotic chemicals have badly affected the environment including human health, ecosystem and environment. Animal-sourced biopolymers have been employed for the removal of heavy metals and organic dyes from the contaminated soil and waste waters. Animal-sourced biopolymers are biocompatible, cost-effective, eco-friendly, and sustainable in nature which make them a favorable choice for the mitigation of xenobiotic and hazardous compounds. Chitin/chitosan, collagen, gelatin, keratin, and silk fibroin-based biopolymers are the most commonly used biopolymers. This chapter reviews the current challenge faced in applying these animal-based biopolymers in eliminating/neutralizing various recalcitrant chemicals and dyes from the environment. This chapter ends with the discussion on the recent advancements and future development in the employability of these biopolymers in such environmental applications.
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Affiliation(s)
- Vipendra Kumar Singh
- School of Biosciences and Bioengineering , Indian Institute of Technology Mandi , VPO Kamand , Mandi , Himachal Pradesh , India
| | - Priya Gunasekaran
- Department of Biotechnology , College of Science and Humanities, SRM Institute of Science and Technology , Ramapuram , Chennai , Tamil Nadu , India
| | - Medha Kumari
- Brainology Research Fellow, Neuroscience and Microplastic Lab , Brainology Scientific Academy of Jharkhand , Ranchi , Jharkhand , India
| | - Dolly Krishnan
- Secretary cum Founder Director, Research Wing , Brainology Scientific Academy of Jharkhand , Ranchi , Jharkhand , India
| | - Vinoth Kumar Ramachandran
- Department of Biotechnology , College of Science and Humanities, SRM Institute of Science and Technology , Ramapuram , Chennai , Tamil Nadu , India
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12
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Qusa MH, Abdelwahed KS, Hill RA, El Sayed KA. S-(-)-Oleocanthal Ex Vivo Modulatory Effects on Gut Microbiota. Nutrients 2023; 15:618. [PMID: 36771326 PMCID: PMC9920009 DOI: 10.3390/nu15030618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/18/2023] [Accepted: 01/19/2023] [Indexed: 01/27/2023] Open
Abstract
Compelling evidence points to the critical role of bioactive extra-virgin olive oil (EVOO) phenolics and gut microbiota (GM) interplay, but reliable models for studying the consequences thereof remain to be developed. Herein, we report an optimized ex vivo fecal anaerobic fermentation model to study the modulation of GM by the most bioactive EVOO phenolic S-(-)-oleocanthal (OC), and impacts therefrom, focusing on OC biotransformation in the gut. This model will also be applicable for characterization of GM interactions with other EVOO phenolics, and moreover, for a broadly diverse range of bioactive natural products. The fecal fermentation media and time, and mouse type and gender, were the major factors varied and optimized to provide better understanding of GM-OC interplay. A novel resin entrapment technique (solid-phase extraction) served to selectively entrap OC metabolites, degradation products, and any remaining fraction of OC while excluding interfering complex fecal medium constituents. The effects of OC on GM compositions were investigated via shallow shotgun DNA sequencing. Robust metabolome analyses identified GM bacterial species selectively altered (population numbers/fraction) by OC. Finally, the topmost OC-affected gut bacterial species of the studied mice were compared with those known to be extant in humans and distributions of these bacteria at different human body sites. OC intake caused significant quantitative and qualitative changes to mice GM, which was also comparable with human GM. Results clearly highlight the potential positive health outcomes of OC as a prospective nutraceutical.
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Affiliation(s)
| | | | | | - Khalid A. El Sayed
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA
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13
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Campana AM, Laue HE, Shen Y, Shrubsole MJ, Baccarelli AA. Assessing the role of the gut microbiome at the interface between environmental chemical exposures and human health: Current knowledge and challenges. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2022; 315:120380. [PMID: 36220576 PMCID: PMC10239610 DOI: 10.1016/j.envpol.2022.120380] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 09/28/2022] [Accepted: 10/04/2022] [Indexed: 05/05/2023]
Abstract
The explosion of microbiome research over the past decade has shed light on the various ways that external factors interact with the human microbiome to drive health and disease. Each individual is exposed to more than 300 environmental chemicals every day. Accumulating evidence indicates that the microbiome is involved in the early response to environmental toxicants and biologically mediates their adverse effects on human health. However, few review articles to date provided a comprehensive framework for research and translation of the role of the gut microbiome in environmental health science. This review summarizes current evidence on environmental compounds and their effect on the gut microbiome, discusses the involved compound metabolic pathways, and covers environmental pollution-induced gut microbiota disorders and their long-term outcomes on host health. We conclude that the gut microbiota may crucially mediate and modify the disease-causing effects of environmental chemicals. Consequently, gut microbiota needs to be further studied to assess the complete toxicity of environmental exposures. Future research in this field is required to delineate the key interactions between intestinal microbiota and environmental pollutants and further to elucidate the long-term human health effects.
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Affiliation(s)
- Anna Maria Campana
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA.
| | - Hannah E Laue
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Yike Shen
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA
| | - Martha J Shrubsole
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, School of Medicine, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Andrea A Baccarelli
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA
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14
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Quazi S. Anti-cancer activity of human gastrointestinal bacteria. Med Oncol 2022; 39:220. [PMID: 36175586 DOI: 10.1007/s12032-022-01771-3] [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: 02/13/2022] [Accepted: 06/14/2022] [Indexed: 06/16/2023]
Abstract
Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human's gastrointestinal tract can create immune response against inflammation and also can develop diseases, including cancer. The bacteria of the gastrointestinal tract of human can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.
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Affiliation(s)
- Sameer Quazi
- GenLab Biosolutions Private Limited, Bangalore, 560043, Karnataka, India.
- Department of Biomedical Sciences, School of Life Sciences, Anglia Ruskin University, Cambridge, UK.
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15
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Góralczyk-Bińkowska A, Szmajda-Krygier D, Kozłowska E. The Microbiota-Gut-Brain Axis in Psychiatric Disorders. Int J Mol Sci 2022; 23:11245. [PMID: 36232548 PMCID: PMC9570195 DOI: 10.3390/ijms231911245] [Citation(s) in RCA: 180] [Impact Index Per Article: 60.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/10/2022] [Accepted: 09/20/2022] [Indexed: 11/16/2022] Open
Abstract
Modulating the gut microbiome and its influence on human health is the subject of intense research. The gut microbiota could be associated not only with gastroenterological diseases but also with psychiatric disorders. The importance of factors such as stress, mode of delivery, the role of probiotics, circadian clock system, diet, and occupational and environmental exposure in the relationship between the gut microbiota and brain function through bidirectional communication, described as "the microbiome-gut-brain axis", is especially underlined. In this review, we discuss the link between the intestinal microbiome and the brain and host response involving different pathways between the intestinal microbiota and the nervous system (e.g., neurotransmitters, endocrine system, immunological mechanisms, or bacterial metabolites). We review the microbiota alterations and their results in the development of psychiatric disorders, including major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD).
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Affiliation(s)
- Aleksandra Góralczyk-Bińkowska
- Department of Microbiology and Experimental Immunology, MOLecoLAB: Lodz Centre of Molecular Studies on Civilisation Diseases, Medical University of Lodz, Mazowiecka 5 Street, 92-215 Lodz, Poland
| | - Dagmara Szmajda-Krygier
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1 Street, 90-151 Lodz, Poland
| | - Elżbieta Kozłowska
- Department of Microbiology and Experimental Immunology, MOLecoLAB: Lodz Centre of Molecular Studies on Civilisation Diseases, Medical University of Lodz, Mazowiecka 5 Street, 92-215 Lodz, Poland
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16
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Bolan S, Seshadri B, Kunhikrishnan A, Grainge I, Talley NJ, Bolan N, Naidu R. Differential toxicity of potentially toxic elements to human gut microbes. CHEMOSPHERE 2022; 303:134958. [PMID: 35595114 DOI: 10.1016/j.chemosphere.2022.134958] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 04/23/2022] [Accepted: 05/10/2022] [Indexed: 06/15/2023]
Abstract
Specific microorganisms in the human gut (i.e., gut microbes) provide mutually beneficial outcomes such as microbial balance by inhibiting the growth of pathogenic organisms, immune system modulation, fermentation of ingested products, and vitamin production. The intake of contaminants including potenially toxic elements (PTEs) can occur through food, air, water and some medicines. The gut microbes not only can be affected by environmental contaminants but they themselves can alter the speciation and bioavailability of these contaminants. This research work was designed to demonstrate the relationship between increasing level of selected PTEs including As, Cd, Pb and Hg on the growth of selected gut microbes. The toxicity of above mentioned PTEs to three gut bacteria (Lactobacillus rhamnosus, Lactobacillus acidophilus and Escherichia coli) was examined. While the toxicity of all the cationic PTEs including Cd, Pb and Hg towards gut bacteria decreased with increasing pH, the anionic As species exhibited an opposite effect. The order of toxicity was Hg > Cd > Pb > As(III)>As(V) for E. coli; and Hg > Cd > As(III)>Pb > As(V) for the two Lactobacillus sp. Arsenite (AsIII) showed higher toxicity than arsenate (AsV) to gut bacteria. While As is an anion, Cd, Pb and Hg are cations and hence their binding capacity to the bacterial cell wall varied based on the charge dependent functional groups. However, the toxic effects of PTEs for a bacteria are controlled by their speciation and bioavailability.
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Affiliation(s)
- Shiv Bolan
- Global Centre for Environmental Remediation, The University of Newcastle, Callaghan, Australia; School of Agriculture and Environment, The University of Western Australia, Perth, WA, 6001, Australia.
| | - Balaji Seshadri
- Global Centre for Environmental Remediation, The University of Newcastle, Callaghan, Australia
| | - Anitha Kunhikrishnan
- Global Centre for Environmental Remediation, The University of Newcastle, Callaghan, Australia
| | - Ian Grainge
- School of Environmental and Life Sciences, The University of Newcastle, Callaghan, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, The University of Newcastle, Callaghan, Australia
| | - Nanthi Bolan
- School of Agriculture and Environment, The University of Western Australia, Perth, WA, 6001, Australia
| | - Ravi Naidu
- Global Centre for Environmental Remediation, The University of Newcastle, Callaghan, Australia
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17
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Ge Y, Ma Y, Zhao M, Wei J, Wu X, Zhang Z, Yang H, Lei H, Wu B. Exploring gabosine and chlorogentisyl alcohol derivatives from a marine-derived fungus as EcGUS inhibitors with informatic assisted approaches. Eur J Med Chem 2022; 242:114699. [PMID: 36001934 DOI: 10.1016/j.ejmech.2022.114699] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 08/02/2022] [Accepted: 08/15/2022] [Indexed: 11/04/2022]
Abstract
β-Glucuronidase catalyzes the cleavage of glucuronosyl-O-bonds, whose inhibitors reduce the level of toxic substances present in the intestine caused by anti-cancer and anti-inflammatory therapies. Herein, we presented a new tool, Bioactive Fractions Filtering Platform (BFFP), which is able to reliably discern active candidate node from crude extracts. The source code for the BFFP is available on GitHub (https://github.com/BioGavin/msbff). With the assistant of BFFP, 25 gabosine and chlorogentisyl alcohol derivatives including 19 new compounds were isolated from a marine-derived fungus Epicoccum sp. GST-5. Compounds 7, 9-15 possessed an unusual hybrid skeleton of gabosine and chlorogentisyl alcohol units. Compounds 9-12, 16 and 17 possessed a novel three-membered spiral ring skeleton with one/two gabosine and one/two chlorogentisyl alcohol units. Compound 25 represented new gabosine-derived skeleton possessing an unusual 6/6/6/5/6 condensed ring system. All isolates were evaluated for in vitro E. coli β-glucuronidase (EcGUS) inhibitory activity. 14 Compounds demonstrated superior inhibitory activity (IC50 = 0.24-4.61 μM) to that of standard d-saccharic acid 1,4-lactone (DSL, IC50 = 56.74 ± 4.01 μM). Compounds with chlorogentisyl alcohol moiety, such as 17 (IC50 = 0.24 ± 0.02 μM) and 1 (IC50 = 0.74 ± 0.03 μM), exhibited the most potent inhibitory activity. Furthermore, literature based QSAR profiling by applying PCA and OPLS analysis was carried out to analyze the features of compounds against EcGUS, revealing that the introduction of substituents able to form polar interactions with binding sites of receptor would lead to more active structures.
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Affiliation(s)
- Yichao Ge
- Ocean College, Zhejiang University, Zhoushan, 321000, China.
| | - Yihan Ma
- Ocean College, Zhejiang University, Zhoushan, 321000, China.
| | - Meilu Zhao
- Ocean College, Zhejiang University, Zhoushan, 321000, China.
| | - Jihua Wei
- Ocean College, Zhejiang University, Zhoushan, 321000, China.
| | - Xiaodan Wu
- Center of Analysis, Zhejiang University, Hangzhou, 310058, China.
| | - Zunjing Zhang
- Lishui Hospital of Traditional Chinese Medicine, Lishui, 323000, China.
| | - Han Yang
- Ocean College, Zhejiang University, Zhoushan, 321000, China.
| | - Houxing Lei
- Lishui Hospital of Traditional Chinese Medicine, Lishui, 323000, China.
| | - Bin Wu
- Ocean College, Zhejiang University, Zhoushan, 321000, China.
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18
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Bixby M, Gennings C, Malecki KMC, Sethi AK, Safdar N, Peppard PE, Eggers S. Individual Nutrition Is Associated with Altered Gut Microbiome Composition for Adults with Food Insecurity. Nutrients 2022; 14:3407. [PMID: 36014913 PMCID: PMC9416073 DOI: 10.3390/nu14163407] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/13/2022] [Accepted: 08/14/2022] [Indexed: 11/17/2022] Open
Abstract
Diet is widely recognized as a key contributor to human gut microbiome composition and function. However, overall nutrition can be difficult to compare across a population with varying diets. Moreover, the role of food security in the relationship with overall nutrition and the gut microbiome is unclear. This study aims to investigate the association between personalized nutrition scores, variation in the adult gut microbiome, and modification by food insecurity. The data originate from the Survey of the Health of Wisconsin and the Wisconsin Microbiome Study. Individual nutrition scores were assessed using My Nutrition Index (MNI), calculated using data from food frequency questionnaires, and additional health history and demographic surveys. Food security and covariate data were measured through self-reported questionnaires. The gut microbiome was assessed using 16S amplicon sequencing of DNA extracted from stool samples. Associations, adjusted for confounding and interaction by food security, were estimated using Weighted Quantile Sum (WQS) regression models with Random Subset and Repeated Holdout extensions (WQSRSRH), with bacterial taxa used as components in the weighted index. Of 643 participants, the average MNI was 66.5 (SD = 31.9), and 22.8% of participants were food insecure. Increased MNI was significantly associated with altered gut microbial composition (β = 2.56, 95% CI = 0.52−4.61), with Ruminococcus, Oscillospira, and Blautia among the most heavily weighted of the 21 genera associated with the MNI score. In the stratified interaction WQSRSRH models, the bacterial taxa most heavily weighted in the association with MNI differed by food security, but the level of association between MNI and the gut microbiome was not significantly different. More bacterial genera are important in the association with higher nutrition scores for people with food insecurity versus food security, including Streptococcus, Parabacteroides Faecalibacterium, and Desulfovibrio. Individual nutrition scores are associated with differences in adult gut microbiome composition. The bacterial taxa most associated with nutrition vary by level of food security. While further investigation is needed, results showed a higher nutrition score was associated with a wider range of bacterial taxa for food insecure vs. secure, suggesting nutritional quality in food insecure individuals is important in maintaining health and reducing disparities.
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Affiliation(s)
- Moira Bixby
- Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA
| | - Chris Gennings
- Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA
| | - Kristen M. C. Malecki
- Population Health Sciences, University of Wisconsin School of Medicine and Public Health, 610 Walnut St., WARF 707, Madison, WI 53726, USA
| | - Ajay K. Sethi
- Population Health Sciences, University of Wisconsin School of Medicine and Public Health, 610 Walnut St., WARF 707, Madison, WI 53726, USA
| | - Nasia Safdar
- Department of Medicine, Division of Infectious Disease, School of Medicine and Public Health, University of Wisconsin-Madison, UW Med. Fndtn. Centennial Bldg., 1685 Highland Ave, Madison, WI 53705, USA
- William S. Middleton Veterans Affairs Medical Center, 2500 Overlook Terrace, Madison, WI 53705, USA
| | - Paul E. Peppard
- Population Health Sciences, University of Wisconsin School of Medicine and Public Health, 610 Walnut St., WARF 707, Madison, WI 53726, USA
| | - Shoshannah Eggers
- Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA
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19
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Patel SM, Young MC. The Identification and Management of Small Intestinal Bacterial Overgrowth. Phys Med Rehabil Clin N Am 2022; 33:587-603. [PMID: 35989053 DOI: 10.1016/j.pmr.2022.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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20
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El Houari A, Ecale F, Mercier A, Crapart S, Laparre J, Soulard B, Ramnath M, Berjeaud JM, Rodier MH, Crépin A. Development of an in vitro Model of Human Gut Microbiota for Screening the Reciprocal Interactions With Antibiotics, Drugs, and Xenobiotics. Front Microbiol 2022; 13:828359. [PMID: 35495704 PMCID: PMC9042397 DOI: 10.3389/fmicb.2022.828359] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 02/09/2022] [Indexed: 11/17/2022] Open
Abstract
Altering the gut microbiota can negatively affect human health. Efforts may be sustained to predict the intended or unintended effects of molecules not naturally produced or expected to be present within the organism on the gut microbiota. Here, culture-dependent and DNA-based approaches were combined to UHPLC-MS/MS analyses in order to investigate the reciprocal interactions between a constructed Human Gut Microbiota Model (HGMM) and molecules including antibiotics, drugs, and xenobiotics. Our HGMM was composed of strains from the five phyla commonly described in human gut microbiota and belonging to Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, and Actinobacteria. Relevantly, the bacterial diversity was conserved in our constructed human gut model through subcultures. Uneven richness distribution was revealed and the sensitivity of the HGMM was mainly affected by antibiotic exposure rather than by drugs or xenobiotics. Interestingly, the constructed model and the individual cultured strains respond with the same sensitivity to the different molecules. UHPLC-MS/MS analyses revealed the disappearance of some native molecules in the supernatants of the HGMM as well as in those of the individual strains. These results suggest that biotransformation of molecules occurred in the presence of our gut microbiota model and the coupled approaches performed on the individual cultures may emphasize new bacterial strains active in these metabolic processes. From this study, the new HGMM appears as a simple, fast, stable, and inexpensive model for screening the reciprocal interactions between the intestinal microbiota and molecules of interest.
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Affiliation(s)
- Abdelaziz El Houari
- UMR CNRS 7267, Laboratoire Ecologie and Biologie des Interactions, Université de Poitiers, Poitiers, France
| | - Florine Ecale
- UMR CNRS 7267, Laboratoire Ecologie and Biologie des Interactions, Université de Poitiers, Poitiers, France
| | - Anne Mercier
- UMR CNRS 7267, Laboratoire Ecologie and Biologie des Interactions, Université de Poitiers, Poitiers, France
| | - Stéphanie Crapart
- UMR CNRS 7267, Laboratoire Ecologie and Biologie des Interactions, Université de Poitiers, Poitiers, France
| | | | | | | | - Jean-Marc Berjeaud
- UMR CNRS 7267, Laboratoire Ecologie and Biologie des Interactions, Université de Poitiers, Poitiers, France
| | - Marie-Hélène Rodier
- UMR CNRS 7267, Laboratoire Ecologie and Biologie des Interactions, Université de Poitiers, Poitiers, France.,Laboratoire de Parasitologie et Mycologie, CHU de Poitiers, Poitiers, France
| | - Alexandre Crépin
- UMR CNRS 7267, Laboratoire Ecologie and Biologie des Interactions, Université de Poitiers, Poitiers, France
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21
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Domestic Environment and Gut Microbiota: Lessons from Pet Dogs. Microorganisms 2022; 10:microorganisms10050949. [PMID: 35630391 PMCID: PMC9143008 DOI: 10.3390/microorganisms10050949] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 04/25/2022] [Accepted: 04/26/2022] [Indexed: 12/12/2022] Open
Abstract
Accumulating data show the involvement of intestinal microbiota in the development and maintenance of numerous diseases. Many environmental factors influence the composition and function of the gut microbiota. An animal model subjected to the same environmental constraints that will allow better characterization of the microbiota–host dialogue is awaited. The domestic dog has physiological, dietary and pathological characteristics similar to those of humans and shares the domestic environment and lifestyle of its owner. This review exposes how the domestication of dogs has brought them closer to humans based on their intrinsic and extrinsic similarities which were discerned through examining and comparing the current knowledge and data on the intestinal microbiota of humans and canines in the context of several spontaneous pathologies, including inflammatory bowel disease, obesity and diabetes mellitus.
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22
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Mousavi SE, Delgado-Saborit JM, Adivi A, Pauwels S, Godderis L. Air pollution and endocrine disruptors induce human microbiome imbalances: A systematic review of recent evidence and possible biological mechanisms. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 816:151654. [PMID: 34785217 DOI: 10.1016/j.scitotenv.2021.151654] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/26/2021] [Accepted: 11/09/2021] [Indexed: 05/25/2023]
Abstract
A rich body of literature indicates that environmental factors interact with the human microbiome and influence its composition and functions contributing to the pathogenesis of diseases in distal sites of the body. This systematic review examines the scientific evidence on the effect of environmental toxicants, air pollutants and endocrine disruptors (EDCs), on compositional and diversity of human microbiota. Articles from PubMed, Embase, WoS and Google Scholar where included if they focused on human populations or the SHIME® model, and assessed the effects of air pollutants and EDCs on human microbiome. Non-human studies, not written in English and not displaying original research were excluded. The Newcastle-Ottawa Scale was used to assess the quality of individual studies. Results were extracted and presented in tables. 31 studies were selected, including 24 related to air pollutants, 5 related to EDCs, and 2 related to EDC using the SHIME® model. 19 studies focussed on the respiratory system (19), gut (8), skin (2), vaginal (1) and mammary (1) microbiomes. No sufficient number of studies are available to observe a consistent trend for most of the microbiota, except for streptococcus and veillionellales for which 9 out of 10, and 3 out of 4 studies suggest an increase of abundance with exposure to air pollution. A limitation of the evidence reviewed is the scarcity of existing studies assessing microbiomes from individual systems. Growing evidence suggests that exposure to environmental contaminants could change the diversity and abundance of resident microbiota, e.g. in the upper and lower respiratory, gastrointestinal, and female reproductive system. Microbial dysbiosis might lead to colonization of pathogens and outgrowth of pathobionts facilitating infectious diseases. It also might prime metabolic dysfunctions disrupting the production of beneficial metabolites. Further studies should elucidate the role of environmental pollutants in the development of dysbiosis and dysregulation of microbiota-related immunological processes.
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Affiliation(s)
- Sayed Esmaeil Mousavi
- Department of Water and Wastewater Treatment, Water and Wastewater Consulting Engineers (Design & Research), Isfahan, Iran
| | - Juana Maria Delgado-Saborit
- Perinatal Epidemiology, Environmental Health and Clinical Research, School of Medicine, Universitat Jaume I, Castellon, Spain; Environmental Research Group, MRC Centre for Environment and Health, Imperial College London, United Kingdom; School of Geography, Earth & Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
| | - Anna Adivi
- Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX 76201, USA
| | - Sara Pauwels
- Department of Public Health and Primary Care, Centre Environment & Health, KU Leuven, Belgium
| | - Lode Godderis
- Department of Public Health and Primary Care, Centre Environment & Health, KU Leuven, Belgium; IDEWE, External Service for Prevention and Protection at work, Interleuvenlaan 58, 3001 Heverlee, Belgium.
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Cheng Y, Zhang J, Gao F, Xu Y, Wang C. Protective effects of 5-aminolevulinic acid against toxicity induced by alpha-cypermethrin to the liver-gut-microbiota axis in zebrafish. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2022; 234:113422. [PMID: 35305352 DOI: 10.1016/j.ecoenv.2022.113422] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 02/24/2022] [Accepted: 03/13/2022] [Indexed: 06/14/2023]
Abstract
To explore whether and how 5-aminolevulinic acid (ALA) can relieve the toxicity to the liver-gut-microbiota axis caused by alpha-cypermethrin (α-CP), adult zebrafish were exposed to α-CP (1.0 µg L-1) with or without 5.0 mg L-1 ALA supplementation. In the present work, the calculated LC50 of α-CP+ALA was 1.15 μg L-1, increasing about 1.16-fold compared with that of α-CP group (0.99 μg L-1), which indicated that ALA can alleviate the toxicity of α-CP. ALA also alleviated the histopathological lesions in the liver and gut induced by α-CP. Transcriptome sequencing of the liver showed that ALA rescues the differential expression of genes involved in the oxidation-reduction, heme metabolism, and complement activation pathways associated with dysfunctions induced by α-CP, and these findings were verified by RT-qPCR analysis and detection of the activities of enzymes in the liver-gut axis. The gut microbiota 16S rRNA sequencing results showed that α-CP alone induced gut microbial dysbiosis, which was efficiently antagonized by ALA due to decreasing the relative abundances of Cetobacterium and 3 major pathogens, and increasing the relative abundances of beneficial genera. Taken together, the results indicate that ALA might be a promising candidate for attenuating the adverse effects caused by pesticide-induced environmental pollution.
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Affiliation(s)
- Yi Cheng
- Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Sciences, China Agricultural University, Beijing 100193, China.
| | - Jie Zhang
- Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Sciences, China Agricultural University, Beijing 100193, China.
| | - Fei Gao
- Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Sciences, China Agricultural University, Beijing 100193, China.
| | - Yong Xu
- Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Sciences, China Agricultural University, Beijing 100193, China.
| | - Chengju Wang
- Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Sciences, China Agricultural University, Beijing 100193, China.
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Palma-Morales M, Mateos A, Rodríguez J, Casuso RA, Huertas JR. Food made us humans: Recent genetic variability and its relevance 2 to the current distribution of macronutrients 3. Nutrition 2022; 101:111702. [DOI: 10.1016/j.nut.2022.111702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 03/09/2022] [Accepted: 04/11/2022] [Indexed: 11/30/2022]
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Li W, Chen X, Li M, Cai Z, Gong H, Yan M. Microplastics as an aquatic pollutant affect gut microbiota within aquatic animals. JOURNAL OF HAZARDOUS MATERIALS 2022; 423:127094. [PMID: 34530278 DOI: 10.1016/j.jhazmat.2021.127094] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 08/18/2021] [Accepted: 08/29/2021] [Indexed: 05/27/2023]
Abstract
The adverse impact of microplastics (MPs) on gut microbiota within aquatic animals depends on the overall effect of chemicals and biofilm of MPs. Thus, it is ideal to fully understand the influences that arise from each or even all of these characteristics, which should give us a whole picture of consequences that are brought by MPs. Harmful effects of MPs on gut microbiota within aquatic organisms start from the ingestion of MPs by aquatic organisms. According to this, the present review will discuss the ingestion of MPs and its following results on gut microbial communities within aquatic animals, in which chemical components, such as plastic polymers, heavy metals and POPs, and the biofilm of MPs would be involved. This review firstly analyzed the impacts of MPs on aquatic organisms in detail about its chemical components and biofilm based on previous relevant studies. At last, the significance of field studies, functional studies and complex dynamics of gut microbial ecology in the future research of MPs affecting gut microbiota is discussed.
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Affiliation(s)
- Weixin Li
- College of Marine Sciences, South China Agricultural University, Guangzhou 510641, China
| | - Xiaofeng Chen
- College of Marine Sciences, South China Agricultural University, Guangzhou 510641, China
| | - Minqian Li
- College of Marine Sciences, South China Agricultural University, Guangzhou 510641, China
| | - Zeming Cai
- College of Marine Sciences, South China Agricultural University, Guangzhou 510641, China
| | - Han Gong
- College of Marine Sciences, South China Agricultural University, Guangzhou 510641, China.
| | - Muting Yan
- College of Marine Sciences, South China Agricultural University, Guangzhou 510641, China; Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
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26
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Zhang P, Zheng L, Duan Y, Gao Y, Gao H, Mao D, Luo Y. Gut microbiota exaggerates triclosan-induced liver injury via gut-liver axis. JOURNAL OF HAZARDOUS MATERIALS 2022; 421:126707. [PMID: 34315018 DOI: 10.1016/j.jhazmat.2021.126707] [Citation(s) in RCA: 96] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 06/26/2021] [Accepted: 07/18/2021] [Indexed: 06/13/2023]
Abstract
Triclosan (TCS) is an antimicrobial ingredient that has been widely incorporated in consumer products. TCS can cause hepatic damage by disturbing lipid metabolism, which is often accompanied with gut microbiota dysbiosis. However, the effects of gut microbiota on the TCS-induced liver injury are still unknown. Therefore, we constructed a mouse model based on five-week-old male C57BL/6 mice to investigate the effects of dietary TCS exposure (40 ppm) on liver injury. We found that TCS treatment for 4 weeks dramatically disturbed gut microbiota homeostasis, resulting in overproduction of lipopolysaccharides (LPS) and deficiency of secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA). In addition, TCS considerably increased intestinal permeability by reducing mucus excretion and expression of tight junction proteins (ZO-1, occludin and claudin 4), which facilitated translocation of LPS. The LPS accumulation in blood contributed to liver injury by triggering the inflammatory response via TLR4 pathway. In summary, this study provides novel insights into the underlying mechanisms of TCS-associated liver injury induced by gut microbiota via the gut-liver axis, and contributes to better interpretation of the health impact of the environmentally emerging contaminant TCS.
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Affiliation(s)
- Peng Zhang
- College of Environmental Sciences and Engineering, Nankai University, Tianjin 300350, China; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046, China
| | - Liyang Zheng
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Yitao Duan
- College of Environmental Sciences and Engineering, Nankai University, Tianjin 300350, China
| | - Yuting Gao
- College of Environmental Sciences and Engineering, Nankai University, Tianjin 300350, China
| | - Huihui Gao
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Daqing Mao
- School of Medicine, Nankai University, Tianjin 300071, China.
| | - Yi Luo
- College of Environmental Sciences and Engineering, Nankai University, Tianjin 300350, China; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046, China.
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27
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Bennett A. Investigating Novel Genetic Markers for Fluoroquinolone Associated Disorders. Cancer Treat Res 2022; 184:161-166. [PMID: 36449196 DOI: 10.1007/978-3-031-04402-1_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Fluoroquinolones (FQs) are among the most commonly prescribed class of antibiotics and have regulatory approval to treat anthrax, pneumonia, unitary tract infections, and sinus infection among other uses.
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Affiliation(s)
- Andrew Bennett
- SONAR (Southern Network on Adverse Reactions) Program, University of South Carolina College of Pharmacy, Columbia, SC, 29208, USA.
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28
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Fu ZD, Selwyn FP, Cui JY, Klaassen CD. RNA-Seq unveiled section-specific host response to lack of gut microbiota in mouse intestine. Toxicol Appl Pharmacol 2021; 433:115775. [PMID: 34715074 DOI: 10.1016/j.taap.2021.115775] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 10/20/2021] [Accepted: 10/21/2021] [Indexed: 01/07/2023]
Abstract
To identify host responses induced by commensal microbiota in intestine, transcriptomes of four sections of the intestine were compared between germ-free (GF) mice and conventional (CV) controls using RNA-Seq. Cuffdiff revealed that jejunum had the highest number of differentially expressed genes (over 2000) between CV and GF mice, followed by large intestine (LI), duodenum, and ileum. Gene set association analysis identified section-specific alterations in pathways associated with the absence of commensal microbiota. For example, in GF mice, cytochrome P450 (Cyp)-mediated xenobiotic metabolism was preferably down-regulated in duodenum and ileum, whereas intermediary metabolism pathways such as protein digestion and amino acid metabolism were preferably up-regulated in duodenum, jejunum, and LI. In GF mice, carboxypeptidase A1 (Cpa1), which is important for protein digestion, was the top most up-regulated gene within the entire transcriptome in duodenum (53-fold) and LI (142-fold). Conversely, fatty acid binding protein 6 (Fabp6/Ibabp), which is important for bile acid intestinal reabsorption, was the top most down-regulated gene in jejunum (358-fold), and the drug-metabolizing enzyme Cyp1a1 was the top most down-regulated gene in ileum (40-fold). Section-specific host transcriptomic response to the absence of intestinal microbiota was also observed for other important physiological pathways such as cell junction, the absorption of small molecules, bile acid homeostasis, and immune response. In conclusion, the present study has revealed section-specific host gene transcriptional alterations in GF mice, highlighting the importance of intestinal microbiota in facilitating the physiological and drug responses of the host intestine.
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Affiliation(s)
- Zidong Donna Fu
- Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA, United States of America
| | - Felcy Pavithra Selwyn
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States of America
| | - Julia Yue Cui
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States of America
| | - Curtis D Klaassen
- Department of Pharmacology, Toxicology, and Therapeutics, School of Medicine, University of Kansas, Kansas City, KS, United States of America.
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29
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Rodrigues ET, Nascimento SF, Pires CL, Godinho LP, Churro C, Moreno MJ, Pardal MA. Determination of intestinal absorption of the paralytic shellfish toxin GTX-5 using the Caco-2 human cell model. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:67256-67266. [PMID: 34247356 DOI: 10.1007/s11356-021-15342-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 07/03/2021] [Indexed: 06/13/2023]
Abstract
Contributing to the human health risk assessment, the present study aims to evaluate the ability of paralytic shellfish toxins (PSTs) to cross the human intestinal epithelium by using the Caco-2 permeability assay. A crude extract prepared from the PST producer dinoflagellate Gymnodinium catenatum strain, GCAT1_L2_16, and the PST analogue gonyautoxin-5 (GTX-5) prepared from a certified reference material (CRM) were tested. In the conditions of the assay, none of the compounds altered Caco-2 viability, or the integrity of cell monolayers. The GTX-5 apparent permeability coefficients are 0.9×10-7 and 0.6×10-7 cm s-1 for the crude extract and CRM, respectively, thus, <10-6 cm s-1, which indicates that humans absorb this PST analogue poorly. The present study also reveals that, during a 90-min exposure, GTX-5 is not metabolised to a high extent by Caco-2 or retained in the Caco-2 cytoplasm. Since it is known that GTX-5 can be found in the spleen, liver or kidney of the victims, as well as in the urine samples of patients who consumed contaminated seafood, further research is needed to clarify the transport mechanisms involved, permeation time and dose-dependence, and the possible role of intestinal microflora.
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Affiliation(s)
- Elsa T Rodrigues
- Centre for Functional Ecology (CFE), Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal.
| | - Susana F Nascimento
- Centre for Functional Ecology (CFE), Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal
| | - Cristiana L Pires
- Coimbra Chemistry Center (CQC), Department of Chemistry, University of Coimbra, 3004-535, Coimbra, Portugal
| | - Lia P Godinho
- Phytoplankton Laboratory, Division of Oceanography and Marine Environment, Department of the Sea and Marine Resources, Portuguese Institute for the Sea and Atmosphere (IPMA), Rua Alfredo Magalhães Ramalho, 6, 1449-006, Lisbon, Portugal
| | - Catarina Churro
- Phytoplankton Laboratory, Division of Oceanography and Marine Environment, Department of the Sea and Marine Resources, Portuguese Institute for the Sea and Atmosphere (IPMA), Rua Alfredo Magalhães Ramalho, 6, 1449-006, Lisbon, Portugal
- Blue Biotechnology and Ecotoxicology (BBE), Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, 4450-208, Matosinhos, Portugal
| | - Maria João Moreno
- Coimbra Chemistry Center (CQC), Department of Chemistry, University of Coimbra, 3004-535, Coimbra, Portugal
| | - Miguel A Pardal
- Centre for Functional Ecology (CFE), Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal
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30
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Next-generation microbial drugs developed from microbiome's natural products. ADVANCES IN GENETICS 2021; 108:341-382. [PMID: 34844715 DOI: 10.1016/bs.adgen.2021.08.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Scientists working in natural products chemistry have been enticed by the current advancements being made in the discovery of novel "magic bullets" from microbes homed to all conceivable environments. Even though researchers continue to face challenges funneling the novel bioactive compounds in the global therapeutic industries, it seems most likely that the discovery of some "hit molecules" with significant biomedical applications is not that far. We applaud novel natural products for their ability to combat the spread of superbugs and aid in the prevention of currently observed antibiotic resistance. This in-depth investigation covers a wide range of microbiomes with a proclivity for synthesizing novel compounds to combat the spread of superbugs. Furthermore, we use this opportunity to explore various groups of secondary metabolites and their biosynthetic pathways in various microbiota found in mammals, insects, and humans. This systematic study, when taken as a whole, offers detail understanding on the biomedical fate of various groups of compounds originated from diverse microbiomes. For gathering all information that has been uncovered and released so far, we have also presented the huge diversity of microbes that are associated with humans and their metabolic products. To conclude, this concrete review suggests novel ideas that will prove immensely helpful in reducing the danger posed by superbugs while also improving the efficacy of antibiotics.
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31
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Eggers S, Safdar N, Kates A, Sethi AK, Peppard PE, Kanarek MS, Malecki KMC. Urinary lead level and colonization by antibiotic resistant bacteria: Evidence from a population-based study. Environ Epidemiol 2021; 5:e175. [PMID: 34909555 PMCID: PMC8663876 DOI: 10.1097/ee9.0000000000000175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 09/28/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Infection by antibiotic resistant bacteria (ARB) is a global health crisis and asymptomatic colonization increases risk of infection. Nonhuman studies have linked heavy metal exposure to the selection of ARB; however, few epidemiologic studies have examined this relationship. This study analyzes the association between urinary lead level and colonization by ARB in a nonclinical human population. METHODS Data came from the Survey of the Health of Wisconsin 2016-2017, and its ancillary Wisconsin Microbiome Study. Urinary lead levels, adjusted for creatinine, were used to assess exposure. ARB included methicillin resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), fluoroquinolone resistant Gram-negative bacilli (RGNB), and Clostridium difficile (C. diff), from skin, nose, and mouth swabs, and saliva and stool samples. Logistic regression, adjusted for covariates, was used to evaluate associations between Pb and ARB. Secondary analysis investigated Pb resistance from ARB isolates. RESULTS Among 695 participants, 239 (34%) tested positive for ARB. Geometric mean urinary Pb (unadjusted) was 0.286 µg/L (95% confidence intervals [CI] = 0.263, 0.312) for ARB negative participants and 0.323 µg/L (95% CI = 0.287, 0.363) for ARB positive participants. Models adjusted for demographics, diet, and antibiotic use showed elevated odds of positive colonization for those in the 95th percentile (vs. below) of Pb exposure (odds ratio [OR] = 2.05, 95% CI = 0.95, 4.44), and associations were highest in urban residents (OR = 2.85, 95% CI = 1.07, 7.59). RGNB isolates were most resistant to Pb. DISCUSSION These novel results suggest that Pb exposure is associated with increased colonization by ARB, and that RGNB are particularly resistant to Pb.
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Affiliation(s)
- Shoshannah Eggers
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin—Madison, Madison, WI
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Nasia Safdar
- Division of Infectious Disease, Department of Medicine, School of Medicine and Public Health, University of Wisconsin—Madison, Madison, WI
- William S. Middleton Veterans Affairs Medical Center, Madison, WI
| | - Ashley Kates
- Division of Infectious Disease, Department of Medicine, School of Medicine and Public Health, University of Wisconsin—Madison, Madison, WI
- William S. Middleton Veterans Affairs Medical Center, Madison, WI
| | - Ajay K. Sethi
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin—Madison, Madison, WI
| | - Paul E. Peppard
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin—Madison, Madison, WI
| | - Marty S. Kanarek
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin—Madison, Madison, WI
- Nelson Institute for Environmental Studies, University of Wisconsin—Madison, Madison, WI
| | - Kristen M. C. Malecki
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin—Madison, Madison, WI
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Zhou H, Yuan Y, Wang H, Xiang W, Li S, Zheng H, Wen Y, Ming Y, Chen L, Zhou J. Gut Microbiota: A Potential Target for Cancer Interventions. Cancer Manag Res 2021; 13:8281-8296. [PMID: 34764691 PMCID: PMC8572730 DOI: 10.2147/cmar.s328249] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 10/19/2021] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota plays a crucial role in many physiological processes in the human body. Dysbiosis can disrupt the intestinal barrier and alter metabolism and immune responses, leading to the development of diseases. Over the past few decades, evidence has accumulated linking changes in the composition of the gut microbiota to dozens of seemingly unrelated conditions, including cancer. Overall, the gut microbiota mainly affects the occurrence and development of cancer by damaging host DNA, forming and maintaining a pro-inflammatory environment, and affecting host immune responses. In addition, the gut microbiota can also affect the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Scientists attempt to improve the efficacy and decrease the toxicity of these treatment modalities by fine-tuning the gut microbiota. The aim of this review is to assist researchers and clinicians in developing new strategies for the detection and treatment of tumors by providing the latest information on the intestinal microbiome and cancer, as well as exploring potential application prospects and mechanisms of action.
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Affiliation(s)
- Hu Zhou
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Yuan Yuan
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China.,Department of Operation and Anaesthesia, Yibin First People's Hospital, Yibin, Sichuan, People's Republic of China
| | - Haorun Wang
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Wei Xiang
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Shenjie Li
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Haowen Zheng
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Yuqi Wen
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Yang Ming
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Ligang Chen
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China.,Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, People's Republic of China.,Neurological Diseases and Brain Function Laboratory, Luzhou, Sichuan, People's Republic of China
| | - Jie Zhou
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China.,Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, People's Republic of China.,Neurological Diseases and Brain Function Laboratory, Luzhou, Sichuan, People's Republic of China
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Ghosh S, Pramanik S. Structural diversity, functional aspects and future therapeutic applications of human gut microbiome. Arch Microbiol 2021; 203:5281-5308. [PMID: 34405262 PMCID: PMC8370661 DOI: 10.1007/s00203-021-02516-y] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 07/29/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023]
Abstract
The research on human gut microbiome, regarded as the black box of the human body, is still at the stage of infancy as the functional properties of the complex gut microbiome have not yet been understood. Ongoing metagenomic studies have deciphered that the predominant microbial communities belong to eubacterial phyla Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, Cyanobacteria, Verrucomicrobia and archaebacterial phylum Euryarchaeota. The indigenous commensal microbial flora prevents opportunistic pathogenic infection and play undeniable roles in digestion, metabolite and signaling molecule production and controlling host's cellular health, immunity and neuropsychiatric behavior. Besides maintaining intestinal health via short-chain fatty acid (SCFA) production, gut microbes also aid in neuro-immuno-endocrine modulatory molecule production, immune cell differentiation and glucose and lipid metabolism. Interdependence of diet and intestinal microbial diversity suggests the effectiveness of pre- and pro-biotics in maintenance of gut and systemic health. Several companies worldwide have started potentially exploiting the microbial contribution to human health and have translated their use in disease management and therapeutic applications. The present review discusses the vast diversity of microorganisms playing intricate roles in human metabolism. The contribution of the intestinal microbiota to regulate systemic activities including gut-brain-immunity crosstalk has been focused. To the best of our knowledge, this review is the first of its kind to collate and discuss the companies worldwide translating the multi-therapeutic potential of human intestinal microbiota, based on the multi-omics studies, i.e. metagenomics and metabolomics, as ready solutions for several metabolic and systemic disorders.
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Affiliation(s)
- Soma Ghosh
- Kolkata Zonal Center, CSIR-National Environmental Engineering Research Institute, i-8 Sector-C, East Kolkata Township, Kolkata, 700107, India.
| | - Sreemanta Pramanik
- Kolkata Zonal Center, CSIR-National Environmental Engineering Research Institute, i-8 Sector-C, East Kolkata Township, Kolkata, 700107, India
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Ed Nignpense B, Francis N, Blanchard C, Santhakumar AB. Bioaccessibility and Bioactivity of Cereal Polyphenols: A Review. Foods 2021; 10:foods10071595. [PMID: 34359469 PMCID: PMC8307242 DOI: 10.3390/foods10071595] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/05/2021] [Accepted: 07/07/2021] [Indexed: 12/12/2022] Open
Abstract
Cereal bioactive compounds, especially polyphenols, are known to possess a wide range of disease preventive properties that are attributed to their antioxidant and anti-inflammatory activity. However, due to their low plasma concentrations after oral intake, there is controversy regarding their therapeutic benefits in vivo. Within the gastrointestinal tract, some cereal polyphenols are absorbed in the small intestine, with the majority accumulating and metabolised by the colonic microbiota. Chemical and enzymatic processes occurring during gastrointestinal digestion modulate the bioactivity and bioaccessibility of phenolic compounds. The interactions between the cereal polyphenols and the intestinal epithelium allow the modulation of intestinal barrier function through antioxidant, anti-inflammatory activity and mucin production thereby improving intestinal health. The intestinal microbiota is believed to have a reciprocal interaction with polyphenols, wherein the microbiome produces bioactive and bioaccessible phenolic metabolites and the phenolic compound, in turn, modifies the microbiome composition favourably. Thus, the microbiome presents a key link between polyphenol consumption and the health benefits observed in metabolic conditions in numerous studies. This review will explore the therapeutic value of cereal polyphenols in conjunction with their bioaccessibility, impact on intestinal barrier function and interaction with the microbiome coupled with plasma anti-inflammatory effects.
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Affiliation(s)
- Borkwei Ed Nignpense
- School of Biomedical Sciences, Charles Sturt University, Locked Bag 588, Wagga Wagga, NSW 2678, Australia; (B.E.N.); (N.F.); (C.B.)
| | - Nidhish Francis
- School of Biomedical Sciences, Charles Sturt University, Locked Bag 588, Wagga Wagga, NSW 2678, Australia; (B.E.N.); (N.F.); (C.B.)
- School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia
| | - Christopher Blanchard
- School of Biomedical Sciences, Charles Sturt University, Locked Bag 588, Wagga Wagga, NSW 2678, Australia; (B.E.N.); (N.F.); (C.B.)
- Australian Research Council (ARC), Industrial Transformation Training Centre (ITTC) for Functional Grains, Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga Wagga, NSW 2650, Australia
| | - Abishek Bommannan Santhakumar
- School of Biomedical Sciences, Charles Sturt University, Locked Bag 588, Wagga Wagga, NSW 2678, Australia; (B.E.N.); (N.F.); (C.B.)
- Australian Research Council (ARC), Industrial Transformation Training Centre (ITTC) for Functional Grains, Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga Wagga, NSW 2650, Australia
- Correspondence: ; Tel.: +61-2-6933-2678
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Wang H, Banerjee N, Liang Y, Wang G, Hoffman KL, Khan MF. Gut microbiome-host interactions in driving environmental pollutant trichloroethene-mediated autoimmunity. Toxicol Appl Pharmacol 2021; 424:115597. [PMID: 34051218 DOI: 10.1016/j.taap.2021.115597] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 05/18/2021] [Accepted: 05/24/2021] [Indexed: 12/15/2022]
Abstract
Trichloroethene (TCE), a widely used industrial solvent, is associated with the development of autoimmune diseases (ADs), including systemic lupus erythematosus and autoimmune hepatitis. Increasing evidence support a linkage between altered gut microbiome composition and the onset of ADs. However, it is not clear how gut microbiome contributes to TCE-mediated autoimmunity, and initial triggers for microbiome-host interactions leading to systemic autoimmune responses remain unknown. To achieve this, female MRL+/+ mice were treated with 0.5 mg/ml TCE for 52 weeks and fecal samples were subjected to 16S rRNA sequencing to determine the microbiome composition. TCE exposure resulted in distinct bacterial community revealed by β-diversity analysis. Notably, we observed reduction in Lactobacillaceae, Rikenellaceae and Bifidobacteriaceae families, and enrichment of Akkermansiaceae and Lachnospiraceae families after TCE exposure. We also observed significantly increased colonic oxidative stress and inflammatory markers (CD14 and IL-1β), and decreased tight junction proteins (ZO-2, occludin and claudin-3). These changes were associated with increases in serum antinuclear and anti-smooth muscle antibodies and cytokines (IL-6 and IL-12), together with increased PD1 + CD4+ T cells in TCE-exposed spleen and liver tissues. Importantly, fecal microbiota transplantation (FMT) using feces from TCE-treated mice to antibiotics-treated mice induced increased anti-dsDNA antibodies and hepatic CD4+ T cell infiltration in the recipient mice. Our studies thus delineate how imbalance in gut microbiome and mucosal redox status together with gut inflammatory response and permeability changes could be the key factors in contributing to TCE-mediated ADs. Furthermore, FMT studies provide a solid support to a causal role of microbiome in TCE-mediated autoimmunity.
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Affiliation(s)
- Hui Wang
- Department of Pathology, University of Texas Medical Branch, TX, United States of America
| | - Nivedita Banerjee
- Department of Pathology, University of Texas Medical Branch, TX, United States of America
| | - Yuejin Liang
- Department of Microbiology and Immunology, University of Texas Medical Branch, TX, United States of America
| | - Gangduo Wang
- Department of Pathology, University of Texas Medical Branch, TX, United States of America
| | - Kristi L Hoffman
- Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America
| | - M Firoze Khan
- Department of Pathology, University of Texas Medical Branch, TX, United States of America.
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Evidences for a Role of Gut Microbiota in Pathogenesis and Management of Epilepsy. Int J Mol Sci 2021; 22:ijms22115576. [PMID: 34070389 PMCID: PMC8197531 DOI: 10.3390/ijms22115576] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/19/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Epilepsy as a chronic neurological disorder is characterized by recurrent, unprovoked epileptic seizures. In about half of the people who suffer from epilepsy, the root cause of the disorder is unknown. In the other cases, different factors can cause the onset of epilepsy. In recent years, the role of gut microbiota has been recognized in many neurological disorders, including epilepsy. These data are based on studies of the gut microbiota–brain axis, a relationship starting by a dysbiosis followed by an alteration of brain functions. Interestingly, epileptic patients may show signs of dysbiosis, therefore the normalization of the gut microbiota may lead to improvement of epilepsy and to greater efficacy of anticonvulsant drugs. In this descriptive review, we analyze the evidences for the role of gut microbiota in epilepsy and hypothesize a mechanism of action of these microorganisms in the pathogenesis and treatment of the disease. Human studies revealed an increased prevalence of Firmicutes in patients with refractory epilepsy. Exposure to various compounds can change microbiota composition, decreasing or exacerbating epileptic seizures. These include antibiotics, epileptic drugs, probiotics and ketogenic diet. Finally, we hypothesize that physical activity may play a role in epilepsy through the modulation of the gut microbiota.
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Utembe W, Kamng'ona AW. Gut microbiota-mediated pesticide toxicity in humans: Methodological issues and challenges in the risk assessment of pesticides. CHEMOSPHERE 2021; 271:129817. [PMID: 33736210 DOI: 10.1016/j.chemosphere.2021.129817] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 01/20/2021] [Accepted: 01/25/2021] [Indexed: 06/12/2023]
Abstract
Many in vivo and in vitro studies have shown that pesticides can disrupt the functioning of gut microbiota (GM), which can lead to many diseases in humans. While the tests developed by the Organization of Economic Cooperation and Development (OECD) are expected to capture most apical effects resulting from GM disruptions, exclusion of GM in the risk assessment might mischaracterize hazards or overestimate/underestimate risks, especially when extrapolating results from one species to another species or population with a substantially different GM. On the other hand, direct assessment of GM-mediated effects may face challenges in identifying hazards, since not all GM perturbations will lead to human adverse effects. In this regard, reliable and validated biomarkers for common GM-mediated adverse effects may be very useful in the identification of GM-mediated pesticide toxicity. Nevertheless, proving causality of GM-mediated effects will need modifications of Bradford Hill criteria as well as Koch's postulates, which are more suitable for the "one-pathogen" paradigm. Furthermore, risk assessment of GM-mediated effects may require pesticide toxicokinetics along the gut, possibly through modeling, and the establishment of the involvement of GM in the mechanism of action (MOA) of the pesticide. Risk assessment of GM mediated effects also requires the standardization of experimental approaches as well as the establishment of microbial reference communities, since variations exist among GM in human populations.
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Affiliation(s)
- Wells Utembe
- Toxicology Department, National Institute for Occupational Health (a division of the National Health Laboratory Service), Johannesburg, 2000, South Africa; Department of Environmental Heath, Faculty of Health Sciences, University of Johannesburg, Johannesburg, 2000, South Africa.
| | - Arox Wadson Kamng'ona
- Department of Biomedical Sciences, College of Medicine, University Of Malawi, Blantyre, Malawi; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
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Zhao J, Luo W, Xu Y, Ling J, Deng L. Potential reproductive toxicity of multi-walled carbon nanotubes and their chronic exposure effects on the growth and development of Xenopus tropicalis. THE SCIENCE OF THE TOTAL ENVIRONMENT 2021; 766:142652. [PMID: 33092835 DOI: 10.1016/j.scitotenv.2020.142652] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 09/23/2020] [Accepted: 09/24/2020] [Indexed: 06/11/2023]
Abstract
The increasing production and use of multi-walled carbon nanotubes (MWCNTs) will inevitably lead to discharge into the environment and exert negative effects on organisms. Many studies have focused on the toxicity of MWCNTs to aquatic animals, but little is known about their possible potential reproductive toxicity. In this study, 6 sexually mature Xenopus tropicalis were exposed to 0.5 and 2.5 mg/L MWCNTs suspensions for 56 days, and the toxicity of MWCNTs to the growth and reproduction of X. tropicalis were studied. The results showed that MWCNTs could inhibit the growth of body, including the testis, ovaries and fat of X. tropicalis. Histopathological section analysis showed that MWCNTs affected the formation of spermatogonia and oocytes, while had no notable effect on the heart or liver. MWCNTs would be accumulated in lungs of X. tropicalis inducing lung cannons. In addition, MWCNTs changed the microbial community structure and diversity of gut microbiota but did not change its abundance significantly. Moreover, MWCNTs could even decrease the fertilized and survival rate of X. tropicalis embryos. These results indicated that chronic exposure to MWCNTs would not only affect the growth and development of X. tropicalis, but also pose a potential risk on their reproduction.
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Affiliation(s)
- Jianbin Zhao
- School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China
| | - Wenshi Luo
- School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China
| | - Yanbin Xu
- School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China; Analysis and Test Center, Guangdong University of Technology, Guangzhou 510006, China.
| | - Jiayin Ling
- School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China
| | - Longhua Deng
- School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China
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Cherif LS, Cao-Lei L, Farinelle S, Muller CP, Turner JD, Schroeder H, Grova N. Assessment of 9-OH- and 7,8-diol-benzo[a]pyrene in Blood as Potent Markers of Cognitive Impairment Related to benzo[a]pyrene Exposure: An Animal Model Study. TOXICS 2021; 9:toxics9030050. [PMID: 33800341 PMCID: PMC7998639 DOI: 10.3390/toxics9030050] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/14/2021] [Accepted: 03/03/2021] [Indexed: 12/27/2022]
Abstract
The potent neurotoxicity of benzo[a]pyrene (B[a]P) has been suggested to be a susceptibility factor accelerating the onset of brain tumours and the emergence of neurobehavioural disturbances. B[a]P has been shown to be neurotoxic, acting directly on both the central and peripheral nervous systems, as well as indirectly via peripheral organs like liver and gut. By using a realistic B[a]P exposure scenario (0.02-200 mg/kg/day, 10 days) in mice, we elucidated brain-specific B[a]P metabolism and at identified hydroxylated B[a]P metabolites in serum which could be used as markers of cognitive impairment. Repeated oral administration of B[a]P led to, at the doses of 20 and 200 mg/kg/day, significant overexpression of Cyp1a1/Cyp1b1 in 2 out of the 3 brain regions considered, thereby suggesting the ability of the brain to metabolize B[a]P itself. At the same doses, mice exhibited a reduction in anxiety in both the elevated plus maze and the hole board apparatus. Concomitantly, B[a]P triggered dose-dependent changes in Nmda subunit expression (Nr1 and Nr2a/Nr2b) in areas involved in cognition. We detected 9-OH-B[a]P and 7,8-diol-B[a]P in serum at the level for which cognitive impairment was observed. We suggest that these metabolites may, in the future be exploited as potent biomarkers of B[a]P-induced cognitive impairments.
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Affiliation(s)
- Lynda Saber Cherif
- Calbinotox, EA7488, Faculty of Science and Technology, Lorraine University, 54500 Vandoeuvre-lès Nancy, France; (L.S.C.); (L.C.-L.); (H.S.)
| | - Lei Cao-Lei
- Calbinotox, EA7488, Faculty of Science and Technology, Lorraine University, 54500 Vandoeuvre-lès Nancy, France; (L.S.C.); (L.C.-L.); (H.S.)
- Immune Endocrine Epigenetics Research Group, Department of Infection and Immunity, LuxembourgInstitute of Health, L-4354 Esch-sur-Alzette, Luxembourg;
| | - Sophie Farinelle
- Experimental & Molecular Immunology Research Group, Department of Infection and Immunity, Luxembourg Institute of Health, L-4354 Esch-sur-Alzette, Luxembourg;
| | - Claude P. Muller
- Department of Infection and Immunity, Luxembourg Institute of Health, L-4354 Esch-Sur-Alzette, Luxembourg;
- Laboratoire National de Santé, L-3583 Dudelange, Luxembourg
| | - Jonathan D. Turner
- Immune Endocrine Epigenetics Research Group, Department of Infection and Immunity, LuxembourgInstitute of Health, L-4354 Esch-sur-Alzette, Luxembourg;
| | - Henri Schroeder
- Calbinotox, EA7488, Faculty of Science and Technology, Lorraine University, 54500 Vandoeuvre-lès Nancy, France; (L.S.C.); (L.C.-L.); (H.S.)
| | - Nathalie Grova
- Calbinotox, EA7488, Faculty of Science and Technology, Lorraine University, 54500 Vandoeuvre-lès Nancy, France; (L.S.C.); (L.C.-L.); (H.S.)
- Immune Endocrine Epigenetics Research Group, Department of Infection and Immunity, LuxembourgInstitute of Health, L-4354 Esch-sur-Alzette, Luxembourg;
- Correspondence: or ; Tel.: +352-26-970-422
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40
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Lin HY, Chen CY, Lin TC, Yeh LF, Hsieh WC, Gao S, Burnouf PA, Chen BM, Hsieh TJ, Dashnyam P, Kuo YH, Tu Z, Roffler SR, Lin CH. Entropy-driven binding of gut bacterial β-glucuronidase inhibitors ameliorates irinotecan-induced toxicity. Commun Biol 2021; 4:280. [PMID: 33664385 PMCID: PMC7933434 DOI: 10.1038/s42003-021-01815-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 02/08/2021] [Indexed: 12/31/2022] Open
Abstract
Irinotecan inhibits cell proliferation and thus is used for the primary treatment of colorectal cancer. Metabolism of irinotecan involves incorporation of β-glucuronic acid to facilitate excretion. During transit of the glucuronidated product through the gastrointestinal tract, an induced upregulation of gut microbial β-glucuronidase (GUS) activity may cause severe diarrhea and thus force many patients to stop treatment. We herein report the development of uronic isofagomine (UIFG) derivatives that act as general, potent inhibitors of bacterial GUSs, especially those of Escherichia coli and Clostridium perfringens. The best inhibitor, C6-nonyl UIFG, is 23,300-fold more selective for E. coli GUS than for human GUS (Ki = 0.0045 and 105 μM, respectively). Structural evidence indicated that the loss of coordinated water molecules, with the consequent increase in entropy, contributes to the high affinity and selectivity for bacterial GUSs. The inhibitors also effectively reduced irinotecan-induced diarrhea in mice without damaging intestinal epithelial cells.
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Affiliation(s)
- Hsien-Ya Lin
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
- Department of Chemistry, National Taiwan University, Taipei, Taiwan
| | - Chia-Yu Chen
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
- Department of Chemistry, National Taiwan University, Taipei, Taiwan
| | - Ting-Chien Lin
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
- Department of Chemistry, National Taiwan University, Taipei, Taiwan
| | - Lun-Fu Yeh
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
| | - Wei-Che Hsieh
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
| | - Shijay Gao
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
| | | | - Bing-Mae Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Tung-Ju Hsieh
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
| | | | - Yen-Hsi Kuo
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
| | - Zhijay Tu
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
| | - Steve R Roffler
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chun-Hung Lin
- Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
- Department of Chemistry, National Taiwan University, Taipei, Taiwan.
- Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
- The Genomics Research Center, Academia Sinica, Taipei, Taiwan.
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41
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Related substances method development and validation of an LCMS/MS method for quantification of selexipag and its related impurities in rat plasma and its application to pharmacokinetic studies. SN APPLIED SCIENCES 2021. [DOI: 10.1007/s42452-021-04219-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
AbstractThe present application wish to seem at the event of validation of bio analytical method and pharmacokinetic study of selexipag and its related impurities in rat plasma using LC–MS/MS. The optimized method contains gradient elution of selexipag with a flow rate of 1 ml/min and X-Bridge phenyl column (150 × 4.6 mm, 3.5 µ). A buffer of 1 mL formic acid in l liter water and acetonitrile mixture is used as mobile phase. 30 min run time was used for separation of selexipag and its related impurities with Ambrisentan as internal standard and impurity-D as active metabolite. The linearity curves are linear in between the percentages of 10 to 200% of rat plasma and R2 value of each analyte was observed as 0.999. This application denotes all the parameters like precision, accuracy, recovery and stability were got the results within the limit of USFDA guidelines. This method applies effectively for the investigation of pharmacokinetic studies using rat plasma.
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Marcos-Fernández R, Ruiz L, Blanco-Míguez A, Margolles A, Sánchez B. Precision modification of the human gut microbiota targeting surface-associated proteins. Sci Rep 2021; 11:1270. [PMID: 33446697 PMCID: PMC7809461 DOI: 10.1038/s41598-020-80187-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 12/14/2020] [Indexed: 01/29/2023] Open
Abstract
This work describes a new procedure that allows the targeted modification of the human gut microbiota by using antibodies raised against bacterial surface-associated proteins specific to the microorganism of interest. To this end, a polyclonal antibody recognising the surface-associated protein Surface Layer Protein A of Lactobacillus acidophilus DSM20079T was developed. By conjugating this antibody with fluorescent probes and magnetic particles, we were able to specifically identify this bacterium both in a synthetic, and in real gut microbiotas by means of a flow cytometry approach. Further, we demonstrated the applicability of this antibody to deplete complex human gut microbiotas from L. acidophilus in a single step. L. acidophilus was found to interact with other bacteria both in synthetic and in real microbiotas, as reflected by its concomitant depletion together with other species. Further optimization of the procedure including a trypsin step enabled to achieve the selective and complete isolation of this species. Depleting a single species from a gut microbiota, using antibodies recognizing specific cell surface elements of the target organism, will open up novel ways to tackle research on the specific immunomodulatory and metabolic contributions of a bacterium of interest in the context of a complex human gut microbiota, including the investigation into therapeutic applications by adding/depleting a key bacterium. This represents the first work in which an antibody/flow-cytometry based application enabled the targeted edition of human gut microbiotas, and represents the basis for the design of precision microbiome-based therapies.
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Affiliation(s)
- Raquel Marcos-Fernández
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Paseo Río Linares s/n, 33300, Villaviciosa, Asturias, Spain
- Functionality and Ecology of Beneficial Microbes (MicroHealth) Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain
| | - Lorena Ruiz
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Paseo Río Linares s/n, 33300, Villaviciosa, Asturias, Spain
- Functionality and Ecology of Beneficial Microbes (MicroHealth) Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain
| | - Aitor Blanco-Míguez
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Paseo Río Linares s/n, 33300, Villaviciosa, Asturias, Spain
- Functionality and Ecology of Beneficial Microbes (MicroHealth) Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain
| | - Abelardo Margolles
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Paseo Río Linares s/n, 33300, Villaviciosa, Asturias, Spain.
- Functionality and Ecology of Beneficial Microbes (MicroHealth) Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain.
| | - Borja Sánchez
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Paseo Río Linares s/n, 33300, Villaviciosa, Asturias, Spain.
- Functionality and Ecology of Beneficial Microbes (MicroHealth) Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain.
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Holmes M, Flaminio Z, Vardhan M, Xu F, Li X, Devinsky O, Saxena D. Cross talk between drug-resistant epilepsy and the gut microbiome. Epilepsia 2020; 61:2619-2628. [PMID: 33140419 DOI: 10.1111/epi.16744] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 09/16/2020] [Accepted: 10/07/2020] [Indexed: 12/14/2022]
Abstract
One-third of epilepsy patients have drug-resistant epilepsy (DRE), which is often complicated by polydrug toxicity and psychiatric and cognitive comorbidities. Advances in understanding the microbiome and gut-brain-axis are likely to shed light on epilepsy pathogenesis, anti-seizure medication (ASM) resistance, and potential therapeutic targets. Gut dysbiosis is associated with inflammation, blood-brain barrier disruption, and altered neuromodulators. High-throughput and metagenomic sequencing has advanced the characterization of microbial species and functional pathways. DRE patients show altered gut microbiome composition compared to drug-sensitive patients and healthy controls. The ketogenic and modified Atkins diets can reduce seizures in some patients with DRE. These low-carbohydrate dietary therapies alter the taxonomic and functional composition of the gut microbiome, and composition varies between diet responders and nonresponders. Murine models suggest that specific phyla are necessary to confer efficacy from the diet, and antibiotic treatment may eliminate efficacy. The impact of diet might involve alterations in microbiota, promotion of select microbial interactions, and variance in brain neurotransmitter levels that then influence seizures. Understanding the mechanics of how diet manipulates seizures may suggest novel therapies. Most ASMs act on neuronal transmission via effects on ion channels and neurotransmitters. However, ASMs may also assert their effects via the gut microbiota. In animal models, the microbiota composition (eg, abundance of certain phyla) can vary with ASM active drug metabolites. Given the developing understanding of the gut microbiome in DRE, probiotics are another potential therapy. Probiotics alter the microbiota composition, and small studies suggest that these supplements can reduce seizures in some patients. DRE has enormous consequences to patients and society, and the gut microbiome holds promise as a potential therapeutic target. However, the exact mechanism and recognition of which patients are likely to be responders remain elusive. Further studies are warranted.
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Affiliation(s)
- Manisha Holmes
- NYU Comprehensive Epilepsy Center, Department of Neurology, New York University Langone Health, New York, NY, USA
| | - Zia Flaminio
- Department of Molecular Pathobiology, New York University College of Dentistry and Department of Surgery, New York University School of Medicine, New York, NY, USA
| | - Mridula Vardhan
- Department of Molecular Pathobiology, New York University College of Dentistry and Department of Surgery, New York University School of Medicine, New York, NY, USA
| | - Fangxi Xu
- Department of Molecular Pathobiology, New York University College of Dentistry and Department of Surgery, New York University School of Medicine, New York, NY, USA
| | - Xin Li
- Department of Molecular Pathobiology, New York University College of Dentistry and Department of Surgery, New York University School of Medicine, New York, NY, USA
| | - Orrin Devinsky
- NYU Comprehensive Epilepsy Center, Department of Neurology, New York University Langone Health, New York, NY, USA
| | - Deepak Saxena
- Department of Molecular Pathobiology, New York University College of Dentistry and Department of Surgery, New York University School of Medicine, New York, NY, USA
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Molecular mechanisms of polysaccharides from Ziziphus jujuba Mill var. spinosa seeds regulating the bioavailability of spinosin and preventing colitis. Int J Biol Macromol 2020; 163:1393-1402. [DOI: 10.1016/j.ijbiomac.2020.07.229] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 07/15/2020] [Accepted: 07/23/2020] [Indexed: 12/12/2022]
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45
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Yadav M, Chauhan NS. Overview of the rules of the microbial engagement in the gut microbiome: a step towards microbiome therapeutics. J Appl Microbiol 2020; 130:1425-1441. [PMID: 33022786 DOI: 10.1111/jam.14883] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/18/2020] [Accepted: 09/26/2020] [Indexed: 12/14/2022]
Abstract
Human gut microbiome is a diversified, resilient, immuno-stabilized, metabolically active and physiologically essential component of the human body. Scientific explorations have been made to seek in-depth information about human gut microbiome establishment, microbiome functioning, microbiome succession, factors influencing microbial community dynamics and the role of gut microbiome in health and diseases. Extensive investigations have proposed the microbiome therapeutics as a futuristic medicine for various physiological and metabolic disorders. A comprehensive outlook of microbial colonization, host-microbe interactions, microbial adaptation, commensal selection and immuno-survivability is still required to catalogue the essential genetic and physiological features for the commensal engagement. Evolution of a structured human gut microbiome relies on the microbial flexibility towards genetic, immunological and physiological adaptation in the human gut. Key features for commensalism could be utilized in developing tailor-made microbiome-based therapy to overcome various physiological and metabolic disorders. This review describes the key genetics and physiological traits required for host-microbe interaction and successful commensalism to institute a human gut microbiome.
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Affiliation(s)
- M Yadav
- Department of Biochemistry, Maharshi Dayanand University, Rohtak, Haryana, India
| | - N S Chauhan
- Department of Biochemistry, Maharshi Dayanand University, Rohtak, Haryana, India
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Elmassry MM, Zayed A, Farag MA. Gut homeostasis and microbiota under attack: impact of the different types of food contaminants on gut health. Crit Rev Food Sci Nutr 2020; 62:738-763. [DOI: 10.1080/10408398.2020.1828263] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Moamen M. Elmassry
- Department of Biological Sciences, Texas Tech University, Lubbock, Texas, USA
| | - Ahmed Zayed
- Department of Pharmacognosy, College of Pharmacy, Tanta University, Tanta, Egypt
- Institute of Bioprocess Engineering, Technical University of Kaiserslautern, Kaiserslautern, Germany
| | - Mohamed A. Farag
- Department of Pharmacognosy, College of Pharmacy, Cairo University, Cairo, Egypt
- Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, New Cairo, Egypt
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Adamovsky O, Buerger AN, Vespalcova H, Sohag SR, Hanlon AT, Ginn PE, Craft SL, Smatana S, Budinska E, Persico M, Bisesi JH, Martyniuk CJ. Evaluation of Microbiome-Host Relationships in the Zebrafish Gastrointestinal System Reveals Adaptive Immunity Is a Target of Bis(2-ethylhexyl) Phthalate (DEHP) Exposure. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2020; 54:5719-5728. [PMID: 32255618 DOI: 10.1021/acs.est.0c00628] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
To improve physical characteristics of plastics such as flexibility and durability, producers enrich materials with phthalates such as di-2-(ethylhexyl) phthalate (DEHP). DEHP is a high production volume chemical associated with metabolic and immune disruption in animals and humans. To reveal mechanisms implicated in phthalate-related disruption in the gastrointestinal system, male and female zebrafish were fed DEHP (3 ppm) daily for two months. At the transcriptome level, DEHP significantly upregulated gene networks in the intestine associated with helper T cells' (Th1, Th2, and Th17) specific pathways. The activation of gene networks associated with adaptive immunity was linked to the suppression of networks for tight junction, gap junctional intercellular communication, and transmembrane transporters, all of which are precursors for impaired gut integrity and performance. On a class level, DEHP exposure increased Bacteroidia and Gammaproteobacteria and decreased Verrucomicrobiae in both the male and female gastrointestinal system. Further, in males there was a relative increase in Fusobacteriia and Betaproteobacteria and a relative decrease in Saccharibacteria. Predictive algorithms revealed that the functional shift in the microbiome community, and the metabolites they produce, act to modulate intestinal adaptive immunity. This finding suggests that the gut microbiota may contribute to the adverse effects of DEHP on the host by altering metabolites sensed by both intestinal and immune Th cells. Our results suggest that the microbiome-gut-immune axis can be modified by DEHP and emphasize the value of multiomics approaches to study microbiome-host interactions following chemical perturbations.
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Affiliation(s)
- Ondrej Adamovsky
- Research Centre for Toxic Compounds in the Environment (RECETOX), Masaryk University, Kamenice 753/5, Brno, Czech Republic
- Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, Florida 32611, United States
| | - Amanda N Buerger
- Department of Environmental and Global Health and Center for Environmental and Human Toxicology, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States
| | - Hana Vespalcova
- Research Centre for Toxic Compounds in the Environment (RECETOX), Masaryk University, Kamenice 753/5, Brno, Czech Republic
| | - Shahadur R Sohag
- Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, Florida 32611, United States
| | - Amy T Hanlon
- Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, Florida 32611, United States
| | - Pamela E Ginn
- Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States
| | - Serena L Craft
- Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States
| | - Stanislav Smatana
- Research Centre for Toxic Compounds in the Environment (RECETOX), Masaryk University, Kamenice 753/5, Brno, Czech Republic
- Brno University of Technology, Faculty of Information Technology, IT4Innovations Centre of Excellence, Bozetechova 2, 61266 Brno, Czech Republic
| | - Eva Budinska
- Research Centre for Toxic Compounds in the Environment (RECETOX), Masaryk University, Kamenice 753/5, Brno, Czech Republic
| | - Maria Persico
- Research Centre for Toxic Compounds in the Environment (RECETOX), Masaryk University, Kamenice 753/5, Brno, Czech Republic
| | - Joseph H Bisesi
- Department of Environmental and Global Health and Center for Environmental and Human Toxicology, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States
| | - Christopher J Martyniuk
- Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, Florida 32611, United States
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Wang J, Hu W, Yang H, Chen F, Shu Y, Zhang G, Liu J, Liu Y, Li H, Guo L. Arsenic concentrations, diversity and co-occurrence patterns of bacterial and fungal communities in the feces of mice under sub-chronic arsenic exposure through food. ENVIRONMENT INTERNATIONAL 2020; 138:105600. [PMID: 32120061 DOI: 10.1016/j.envint.2020.105600] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 02/09/2020] [Accepted: 02/19/2020] [Indexed: 06/10/2023]
Abstract
BACKGROUND Arsenic, a global pollutant and a threshold-free primary carcinogen, can accumulate in rice. Previous studies have focused on arsenic poisoning in drinking water and the effects on gut microbes. The research on arseniasis through food, which involves the bio-transformation of arsenic, and the related changes in gut microbiome is insufficient. METHOD Mice were exposed from animal feed prepared with four arsenic species (iAsIII, iAsV, MMA, and DMA) at a dose of 30 mg/kg according to the arsenic species proportion in rice for 30 days and 60 days. The levels of total arsenic (tAs) and arsenic species in mice feces and urine samples were determined using ICP-MS and HPLC-ICP-MS, respectively. 16S rRNA and ITS gene sequencing were conducted on microbial DNA extracted from the feces samples. RESULTS At 30 days and 60 days exposure, the tAs levels excreted from urine were 0.0092 and 0.0093 mg/day, and tAs levels in feces were 0.0441 and 0.0409 mg/day, respectively. We found significant differences in arsenic species distribution in urine and feces (p < 0.05). In urine, the predominant arsenic species were iAsIII (23% and 14%, respectively), DMA (55% and 70%, respectively), and uAs (unknown arsenic, 14% and 10%, respectively). In feces, the proportion of major arsenic species (iAsV, 26% and 21%; iAsIII, 16% and 15%; MMA, 14% and 14%; DMA, 19% and 19%; and uAs, 22% and 29%, respectively) were evenly distributed. Microbiological analysis (MRPP test, α- and β-diversities) showed that diversity of gut bacteria was significantly related to arsenic exposure through food, but diversity of gut fungi is less affected. Manhattan plot and LEfSe analysis showed that arsenic exposure significantly changes microbial taxa, which might be directly associated with arsenic metabolism and diseases mediated by arsenic exposure, such as Deltaproteobacteria, Polynucleobacter, Saccharomyces, Candida, Amanitaceae, and Fusarium. Network analysis was used to identify the changing hub taxa in feces along with arsenic exposure. Function predicting analysis indicated that arsenic exposure might also significantly increase differential metabolic pathways and would disturb carbohydrates, lipid, and amino acids metabolism of gut bacteria. CONCLUSIONS The results demonstrate that subchronic arsenic exposure via food significantly changes the gut microbiome, and the toxicity of arsenic in food, especially in staples, should be comprehensively evaluated in terms of the disturbance of microbiome, and feces might be the main pathway through which arsenic from food exposure is excreted and bio-transformed, providing a new insight into the investigation of bio-detoxification for arseniasis.
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Affiliation(s)
- Jiating Wang
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
| | - Wei Hu
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
| | - Huilin Yang
- Nanchang Key Laboratory of Microbial Resources Exploitation & Utilization from Poyang Lake Wetland, Jiangxi Normal University, Nanchang 330022, China.
| | - Fubin Chen
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
| | - Yanling Shu
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
| | - Guiwei Zhang
- Shenzhen Academy of Metrology and Quality Inspection, Shenzhen 518000, China.
| | - Jizhen Liu
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
| | - Yungang Liu
- Department of Toxicology, School of Public Health, Southern Medical University, 1023 S. Shatai Road, Guangzhou 510515, China.
| | - Huawen Li
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
| | - Lianxian Guo
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
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Bi Y, Marcus AK, Robert H, Krajmalnik-Brown R, Rittmann BE, Westerhoff P, Ropers MH, Mercier-Bonin M. The complex puzzle of dietary silver nanoparticles, mucus and microbiota in the gut. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART B, CRITICAL REVIEWS 2020; 23:69-89. [PMID: 31920169 DOI: 10.1080/10937404.2019.1710914] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Hundreds of consumer and commercial products containing silver nanoparticles (AgNPs) are currently used in food, personal-care products, pharmaceutical, and many other applications. Human exposure to AgNPs includes oral intake, inhalation, and dermal contact. The aim of this review was to focus on oral intake, intentional and incidental of AgNPs where well-known antimicrobial characteristics that might affect the microbiome and mucus in the gastrointestinal tract (GIT). This critical review summarizes what is known regarding the impacts of AgNPs on gut homeostasis. It is fundamental to understand the forms of AgNPs and their physicochemical characterization before and during digestion. For example, lab-synthesized AgNPs differ from "real" ingestable AgNPs used as food additives and dietary supplements. Similarly, the gut environment alters the chemical and physical state of Ag that is ingested as AgNPs. Emerging research on in vitro and in vivo rodent and human indicated complex multi-directional relationships among AgNPs, the intestinal microbiota, and the epithelial mucus. It may be necessary to go beyond today's descriptive approach to a modeling-based ecosystem approach that might quantitatively integrate spatio-temporal interactions among microbial groups, host factors (e.g., mucus), and environmental factors, including lifestyle-based stressors. It is suggested that future research (1) utilize more representative AgNPs, focus on microbe/mucus interactions, (2) assess the effects of environmental stressors for longer and longitudinal conditions, and (3) be integrated using quantitative modeling.
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Affiliation(s)
- Yuqiang Bi
- Nanosystems Engineering Research Center for Nanotechnology-Enabled Water Treatment, Arizona State University, Tempe, AZ, USA
- School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ, USA
| | - Andrew K Marcus
- Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ, USA
| | - Hervé Robert
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Rosa Krajmalnik-Brown
- School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ, USA
- Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ, USA
| | - Bruce E Rittmann
- School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ, USA
- Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, AZ, USA
| | - Paul Westerhoff
- Nanosystems Engineering Research Center for Nanotechnology-Enabled Water Treatment, Arizona State University, Tempe, AZ, USA
- School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ, USA
| | | | - Muriel Mercier-Bonin
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France
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Nakov R, Velikova T. Chemical Metabolism of Xenobiotics by Gut Microbiota. Curr Drug Metab 2020; 21:260-269. [PMID: 32124693 DOI: 10.2174/1389200221666200303113830] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 01/05/2020] [Accepted: 02/12/2020] [Indexed: 02/08/2023]
Abstract
Among the gut microbiota's newly explored roles in human biology is the ability to modify the chemical structures of foreign compounds (xenobiotics). A growing body of evidence has now provided sufficient acumen on the role of the gut microbiota on xenobiotic metabolism, which could have an intense impact on the therapy for various diseases in the future. Gut microbial xenobiotic metabolites have altered bioavailability, bioactivity and toxicity and can intervene with the actions of human xenobiotic-metabolizing enzymes to affect the destiny of other ingested molecules. These modifications are diverse and could lead to physiologically important consequences. In the current manuscript we aim to review the data currently available on how the gut microbiota directly modifies drugs, dietary compounds, chemicals, pollutants, pesticides and herbal supplements.
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Affiliation(s)
- Radislav Nakov
- Clinic of Gastroenterology, Tsaritsa Yoanna University Hospital, Medical University of Sofia, Sofia, Bulgaria
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