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Soliman N, Kruithoff C, San Valentin EM, Gamal A, McCormick TS, Ghannoum M. Small Intestinal Bacterial and Fungal Overgrowth: Health Implications and Management Perspectives. Nutrients 2025; 17:1365. [PMID: 40284229 PMCID: PMC12030604 DOI: 10.3390/nu17081365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Revised: 04/09/2025] [Accepted: 04/10/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND/OBJECTIVES Small Intestinal Bacterial Overgrowth (SIBO) and Small Intestinal Fungal Overgrowth (SIFO) are distinct yet often overlapping conditions characterized by an abnormal increase in microbial populations within the small intestine. SIBO results from an overgrowth of colonic bacteria, while SIFO is driven by fungal overgrowth, primarily involving Candida species. Both conditions present with nonspecific gastrointestinal (GI) symptoms such as bloating, abdominal pain, diarrhea, and malabsorption, making differentiation between SIBO and SIFO challenging. This review aims to elucidate the underlying mechanisms, risk factors, diagnostic challenges, and management strategies associated with SIBO and SIFO. METHODS A comprehensive review of current literature was conducted, focusing on the pathophysiology, diagnostic modalities, and therapeutic approaches for SIBO and SIFO. RESULTS SIBO is commonly associated with factors such as reduced gastric acid secretion, impaired gut motility, and structural abnormalities like bowel obstruction and diverticula. It is frequently diagnosed using jejunal aspirates (≥105 colony forming units (CFUs)/mL) or breath tests. In contrast, SIFO is linked to prolonged antibiotic use, immunosuppression, and gut microbiome dysbiosis, with diagnosis relying on fungal cultures from small intestinal aspirates due to the absence of standardized protocols. CONCLUSION The clinical overlap and frequent misdiagnosis of SIBO and SIFO highlight the need for improved diagnostic tools and a multidisciplinary approach to management. This review emphasizes the importance of understanding the mechanisms behind SIBO and SIFO, how they relate to other health outcomes, and potential management strategies to optimize patient care and therapeutic outcomes.
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Affiliation(s)
- Natalie Soliman
- Heritage College of Osteopathic Medicine, Ohio University, Cleveland, OH 44122, USA
| | - Caroline Kruithoff
- Heritage College of Osteopathic Medicine, Ohio University, Cleveland, OH 44122, USA
| | - Erin Marie San Valentin
- Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Ahmed Gamal
- University Hospitals St. John Medical Center, Cleveland, OH 44145, USA
| | - Thomas S. McCormick
- Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Mahmoud Ghannoum
- Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA
- Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
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Floyd HEE, Kavanagh AM, Lowe GJ, Amado M, Fraser JA, Blaskovich MAT, Elliott AG, Zuegg J. Standardisation of high throughput microdilution antifungal susceptibility testing for Candida albicans and Cryptococcus neoformans. Sci Rep 2024; 14:23407. [PMID: 39379501 PMCID: PMC11461513 DOI: 10.1038/s41598-024-74068-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 09/23/2024] [Indexed: 10/10/2024] Open
Abstract
The Clinical and Laboratory Standards Institute (CLSI) M27 guidelines are the recommended and most commonly used protocols for broth microdilution antifungal susceptibility testing of yeasts. However, these guidelines are limited to the use of 96-well assay plates, limiting assay capacity. With the increased risk of fungal resistance emerging in the community, it is important to have alternative protocols available, that offer higher throughput and can screen more than eight to ten potential antifungal compounds per plate. This study presents an optimised broth microdilution minimum inhibitory concentration (MIC) method for testing the susceptibility of yeasts in an efficient high throughput screening setup, with minimal growth variability and maximum reproducibility. We extend the M27 guidelines and optimise the conditions for 384-well plates. Validation of the assay was performed with ten clinically used antifungals (fluconazole, amphotericin B, 5-fluorocytosine, posaconazole, voriconazole, ketoconazole, itraconazole, caspofungin diacetate, anidulafungin and micafungin) against Candida albicans and Cryptococcus neoformans.
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Affiliation(s)
- Holly E E Floyd
- Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
| | - Angela M Kavanagh
- Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
| | - Gabrielle J Lowe
- Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
| | - Maite Amado
- Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
| | - James A Fraser
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Mark A T Blaskovich
- Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
| | - Alysha G Elliott
- Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
| | - Johannes Zuegg
- Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
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Mehta A, Yadav M, Gupta BK, Thapa B, Rai J, Thapa SB, Yadav SK, Yadav D, Sharma MR. Multiple brain abscesses in a neonate: a rare case report along with review of literature. Ann Med Surg (Lond) 2024; 86:4793-4798. [PMID: 39118725 PMCID: PMC11305707 DOI: 10.1097/ms9.0000000000002155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 04/30/2024] [Indexed: 08/10/2024] Open
Abstract
Introduction and importance Brain abscess (BA) is a pyogenic infection of the brain parenchyma caused by various organisms. Multiple BAs are uncommon in neonates, and Candida albicans as a causative agent is very rare. If left untreated, BAs are invariably fatal. Early diagnosis, prompt surgical intervention, simultaneous eradication of the primary source, and high-dose intravenous antibiotics decrease the incidence of morbidity and mortality. Case presentation A 20-day-old newborn, delivered normally at term with a full APGAR score, presented with a 5-day history of fever, decreased activity, jaundice, and seizures. Imaging identified multiple cerebral cysts, diagnosed as multiple cerebral abscesses. Treatment involved intraoperative USG-guided burr-hole drainage, followed by a 6-week antifungal therapy course. C. albicans was found to be the causative organism following microscopic examination and culture of the pus. Clinical discussion This literature highlights the rarity of fungal involvement in multiple cerebral abscesses in neonates. Managing such cases is very challenging, as the presentation may mimic bacterial infections. The importance of considering fungi as a causative agent in treatment decisions is crucial. Conclusion Multiple BAs of fungal origin are extremely rare. Early detection and management of cases can reduce mortality among neonates.
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Affiliation(s)
- Aanand Mehta
- Tribhuvan University Teaching Hospital, Maharajgunj
| | - Manish Yadav
- Maharajgunj Medical Campus, Tribhuvan University
| | | | - Bikash Thapa
- Tribhuvan University Teaching Hospital, Maharajgunj
| | - Junu Rai
- Tribhuvan University Teaching Hospital, Maharajgunj
| | | | | | - Digraj Yadav
- Maharajgunj Medical Campus, Tribhuvan University
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Niode NJ, Kepel BJ, Hessel SS, Kairupan TS, Tallei TE. Rhynchophorus ferrugineus larvae: A novel source for combating broad-spectrum bacterial and fungal infections. Vet World 2024; 17:156-170. [PMID: 38406375 PMCID: PMC10884581 DOI: 10.14202/vetworld.2024.156-170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 12/21/2023] [Indexed: 02/27/2024] Open
Abstract
Antimicrobial resistance is a growing concern due to the growth of antibiotic-resistant microorganisms, which makes it difficult to treat infection. Due to its broad-spectrum antimicrobial properties against a diverse array of bacteria, both Gram-positive and Gram-negative bacteria, and fungi, Rhynchophorus ferrugineus larval antimicrobial peptides (AMPs) have demonstrated potential as antimicrobial agents for the treatment of microbial infections and prevention of antibiotic resistance. This study emphasizes the unexplored mechanisms of action of R. ferrugineus larvae against microorganisms. Among the most widely discussed mechanisms is the effect of AMPs in larvae in response to a threat or infection. Modulation of immune-related genes in the intestine and phagocytic capacity of its hemocytes may also affect the antimicrobial activity of R. ferrugineus larvae, with an increase in phenoloxidase activity possibly correlated with microbial clearance and survival rates of larvae. The safety and toxicity of R. ferrugineus larvae extracts, as well as their long-term efficacy, are also addressed in this paper. The implications of future research are explored in this paper, and it is certain that R. ferrugineus larvae have the potential to be developed as a broad-spectrum antimicrobial agent with proper investigation.
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Affiliation(s)
- Nurdjannah Jane Niode
- Department of Dermatology and Venereology, Faculty of Medicine, Sam Ratulangi University, Prof. Dr. R. D. Kandou Hospital Manado, Manado 95115, North Sulawesi, Indonesia
| | - Billy Johnson Kepel
- Department of Chemistry, Faculty of Medicine, Sam Ratulangi University, Manado 95115, North Sulawesi, Indonesia
| | - Sofia Safitri Hessel
- Department of Biotechnology, Indonesia Biodiversity and Biogeography Research Institute (INABIG), Bandung 40132, West Java, Indonesia
| | - Tara Sefanya Kairupan
- Department of Dermatology and Venereology, Faculty of Medicine, Sam Ratulangi University, Prof. Dr. R. D. Kandou Hospital Manado, Manado 95115, North Sulawesi, Indonesia
| | - Trina Ekawati Tallei
- Department of Biology, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, North Sulawesi, Indonesia
- Department of Biology, Faculty of Medicine, Sam Ratulangi University, Manado 95115, North Sulawesi, Indonesia
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Chwastowski J, Wójcik K, Kołoczek H, Oszczęda Z, Khachatryan K, Tomasik P. Effect of water treatment with low-temperature and low-pressure glow plasma of low frequency on the growth of selected microorganisms. INTERNATIONAL JOURNAL OF FOOD PROPERTIES 2023. [DOI: 10.1080/10942912.2023.2169708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- Jarosław Chwastowski
- Institute of Chemistry and Inorganic Technology, Krakow University of Technology, Krakow, Poland
| | - Katarzyna Wójcik
- Central Laboratory for Diagnostics of Tuberculosis Mycobacterium, John Paul the IInd, Hospital, Krakow, Poland
| | - Henryk Kołoczek
- Institute of Chemistry and Inorganic Technology, Krakow University of Technology, Krakow, Poland
| | | | - Karen Khachatryan
- Faculty of Food Technology, University of Agriculture in Krakow, Krakow, Poland
| | - Piotr Tomasik
- Nantes Nanotechnological Systems, Bolesławiec, Poland
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Lim J, Rezaie A. Irritable Bowel Syndrome-Like Symptoms in Quiescent Inflammatory Bowel Disease: A Practical Approach to Diagnosis and Treatment of Organic Causes. Dig Dis Sci 2023; 68:4081-4097. [PMID: 37695549 PMCID: PMC10570178 DOI: 10.1007/s10620-023-08095-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 08/23/2023] [Indexed: 09/12/2023]
Abstract
BACKGROUND Despite achieving remission in inflammatory bowel disease (IBD), persistent gastrointestinal symptoms are common in quiescent IBD. While irritable bowel syndrome (IBS) is commonly diagnosed in IBD, IBS-like symptoms of recurrent abdominal pain and altered bowel habits can also be attributed to a wide range of overlapping gastrointestinal (GI) etiologies and systemic disorders with GI manifestations that often do not respond to conventional IBS therapies. Delay in diagnosis of these conditions can lead to ongoing patient suffering, reduced quality of life, repetition of invasive testing, increased healthcare utilization, and potentially unnecessary empirical escalation of IBD-related treatments. AIMS This review provides a practical approach for the evaluation and diagnosis of IBS mimickers in IBD. We summarize the definition, pathophysiology, diagnosis and treatment of the potential etiologies causing unexplained GI symptoms. CONCLUSION Overlapping conditions can co-exist with IBD and explain IBS-like symptoms. The diagnostic work-up in this population should be individualized and tailored to the predominant symptom pattern, associated clinical signs and symptoms and predisposing conditions that can be obtained from a detailed history and physical examination.
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Affiliation(s)
- Jane Lim
- GI Motility Program, Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, 8730 Alden Drive, Thalians Bldg, #E203, Los Angeles, CA, 90048, USA.
| | - Ali Rezaie
- GI Motility Program, Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, 8730 Alden Drive, Thalians Bldg, #E203, Los Angeles, CA, 90048, USA
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7
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Arafa SH, Elbanna K, Osman GEH, Abulreesh HH. Candida diagnostic techniques: a review. JOURNAL OF UMM AL-QURA UNIVERSITY FOR APPLIED SCIENCES 2023; 9:360-377. [DOI: 10.1007/s43994-023-00049-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 04/27/2023] [Indexed: 01/03/2025]
Abstract
AbstractFungal infections (mycoses) represent a major health issue in humans. They have emerged as a global concern for medical professionals by causing high morbidity and mortality. Fungal infections approximately impact one billion individuals per annum and account for 1.6 million deaths. The diagnosis of Candida infections is a challenging task. Laboratory-based Candida species identification techniques (molecular, commercial, and conventional) have been reviewed and summarized. This review aims to discuss the mycoses history, taxonomy, pathogenicity, and virulence characteristics.
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Umarje SC, Banerjee SK. Non-traditional approaches for control of antibiotic resistance. Expert Opin Biol Ther 2023; 23:1113-1135. [PMID: 38007617 DOI: 10.1080/14712598.2023.2279644] [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: 08/28/2023] [Accepted: 11/01/2023] [Indexed: 11/27/2023]
Abstract
INTRODUCTION The drying up of antibiotic pipeline has necessitated the development of alternative therapeutic strategies to control the problem of antimicrobial resistance (AMR) that is expected to kill 10-million people annually by 2050. Newer therapeutic approaches address the shortcomings of traditional small-molecule antibiotics - the lack of specificity, evolvability, and susceptibility to mutation-based resistance. These 'non-traditional' molecules are biologicals having a complex structure and mode(s) of action that makes them resilient to resistance. AREAS COVERED This review aims to provide information about the non-traditional drug development approaches to tackle the problem of antimicrobial resistance, from the pre-antibiotic era to the latest developments. We have covered the molecules under development in the clinic with literature sourced from reviewed scholarly articles, official company websites involved in innovation of concerned therapeutics, press releases from the regulatory bodies, and clinical trial databases. EXPERT OPINION Formal introduction of non-traditional therapies in general practice can be quick and feasible only if supported with companion diagnostics and used in conjunction with established therapies. Owing to relatively higher development costs, non-traditional therapeutics require more funding as well as well as clarity in regulatory and clinical path. We are hopeful these issues are adequately addressed before AMR develops into a pandemic.
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Affiliation(s)
- Siddharth C Umarje
- Department of Proteomics, AbGenics Life Sciences Pvt. Ltd., Pune, India
- AbGenics Life Sciences Pvt. Ltd., Pune, India
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Lipski L, Rountree R. Integrative and Functional Nutrition: A Clinical Conversation with Liz Lipski, PhD, CNS, FACN, BCHN, IFMCP, LDN, and Robert Rountree, MD. INTEGRATIVE AND COMPLEMENTARY THERAPIES 2023; 29:49-56. [DOI: 10.1089/ict.2023.29068.lli] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Affiliation(s)
- Liz Lipski
- Liz Lipski, PhD, CNS, FACN, BCHN, IFMCP, LDN, is the founder of Innovative Healing, a nutrition education company, an educator for the Institute for Functional Medicine's GI Module, and an advisor for the Accreditation Council for Nutrition Professional Education (ACNPE)
| | - Robert Rountree
- Robert Rountree, MD, practices family medicine in Boulder, Colorado, USA
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Tansel A, Levinthal DJ. Understanding Our Tests: Hydrogen-Methane Breath Testing to Diagnose Small Intestinal Bacterial Overgrowth. Clin Transl Gastroenterol 2023; 14:e00567. [PMID: 36744854 PMCID: PMC10132719 DOI: 10.14309/ctg.0000000000000567] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 01/26/2023] [Indexed: 02/07/2023] Open
Abstract
There is increasing appreciation that small intestinal bacterial overgrowth (SIBO) drives many common gastrointestinal symptoms, including diarrhea, bloating, and abdominal pain. Breath testing via measurement of exhaled hydrogen and methane gases following ingestion of a readily metabolized carbohydrate has become an important noninvasive testing paradigm to help diagnose SIBO. However, because of a number of physiological and technical considerations, how and when to use breath testing in the diagnosis of SIBO remains a nuanced clinical decision. This narrative review provides a comprehensive overview of breath testing paradigms including the indications for testing, how to administer the test, and how patient factors influence breath testing results. We also explore the performance characteristics of breath testing (sensitivity, specificity, positive and negative predictive values, likelihood ratios, and diagnostic odds ratio). Additionally, we describe complementary and alternative tests for diagnosing SIBO. We discuss applications of breath testing for research. Current estimates of SIBO prevalence among commonly encountered high-risk populations are reviewed to provide pretest probability estimates under a variety of clinical situations. Finally, we discuss how to integrate breath test performance characteristics into clinical care decisions using clinical predictors and the Fagan nomogram.
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Affiliation(s)
- Aylin Tansel
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, USA
| | - David J. Levinthal
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, USA
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Banaszak M, Górna I, Woźniak D, Przysławski J, Drzymała-Czyż S. Association between Gut Dysbiosis and the Occurrence of SIBO, LIBO, SIFO and IMO. Microorganisms 2023; 11:573. [PMID: 36985147 PMCID: PMC10052891 DOI: 10.3390/microorganisms11030573] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 02/21/2023] [Accepted: 02/22/2023] [Indexed: 03/03/2023] Open
Abstract
Gut microbiota is the aggregate of all microorganisms in the human digestive system. There are 1014 CFU/mL of such microorganisms in the human body, including bacteria, viruses, fungi, archaea and protozoa. The Firmicutes and Bacteroidetes bacteria phyla comprise 90% of the human gut microbiota. The microbiota support the healthy functioning of the human body by helping with digestion (mainly via short-chain fatty acids and amino acids) and producing short-chain fatty acids. In addition, it exhibits many physiological functions, such as forming the intestinal epithelium, intestinal integrity maintenance, the production of vitamins, and protection against pathogens. An altered composition or the number of microorganisms, known as dysbiosis, disrupts the body's homeostasis and can lead to the development of inflammatory bowel disease, irritable bowel syndrome, and metabolic diseases such as diabetes, obesity and allergies. Several types of disruptions to the gut microbiota have been identified: SIBO (Small Intestinal Bacterial Overgrowth), LIBO (Large Intestinal Bacterial Overgrowth), SIFO (Small Intestinal Fungal Overgrowth), and IMO (Intestinal Methanogen Overgrowth). General gastrointestinal problems such as abdominal pain, bloating, gas, diarrhoea and constipation are the main symptoms of dysbiosis. They lead to malabsorption, nutrient deficiencies, anaemia and hypoproteinaemia. Increased lipopolysaccharide (LPS) permeability, stimulating the inflammatory response and resulting in chronic inflammation, has been identified as the leading cause of microbial overgrowth in the gut. The subject literature is extensive but of limited quality. Despite the recent interest in the gut microbiome and its disorders, more clinical research is needed to determine the pathophysiology, effective treatments, and prevention of small and large intestinal microbiota overgrowth. This review was designed to provide an overview of the available literature on intestinal microbial dysbiosis (SIBO, LIBO, SIFO and IMO) and to determine whether it represents a real threat to human health.
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Affiliation(s)
- Michalina Banaszak
- Department of Bromatology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
- Poznan University of Medical Sciences Doctoral School, Poznan University of Medical Sciences, Bukowska 70, 60-812 Poznan, Poland
| | - Ilona Górna
- Department of Bromatology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Dagmara Woźniak
- Department of Bromatology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
- Poznan University of Medical Sciences Doctoral School, Poznan University of Medical Sciences, Bukowska 70, 60-812 Poznan, Poland
| | - Juliusz Przysławski
- Department of Bromatology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Sławomira Drzymała-Czyż
- Department of Bromatology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
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Li J, Chen D, Yu B, He J, Huang Z, Zheng P, Mao X, Li H, Yu J, Luo J, Yan H, Luo Y. Batch and sampling time exert a larger influence on the fungal community than gastrointestinal location in model animals: A meaningful case study. Front Nutr 2022; 9:1021215. [PMID: 36419550 PMCID: PMC9676510 DOI: 10.3389/fnut.2022.1021215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 10/11/2022] [Indexed: 11/09/2022] Open
Abstract
Fungi play a fundamental role in the intestinal ecosystem and health, but our knowledge of fungal composition and distribution in the whole gastrointestinal tract (GIT) is very limited. The physiological similarity between humans and pigs in terms of digestive and associated metabolic processes places, the pig in a superior position over other non-primate models. Here, we aimed to characterize the diversity and composition of fungi in the GIT of pigs. Using high-throughput sequencing, we evaluated the fungal community in different locations of GIT of 11 pigs with 128.41 ± 1.25 kg body weight acquired successively. Among them, five pigs are sacrificed in April 2019 (Batch 1) and the other six are sacrificed in January 2020 (Batch 2). All subjects with similar genetic backgrounds, housing, management, and diet. Finally, no significant difference is found in the α-diversity (Richness) of the fungal community among all intestinal segments. Basidiomycota and Ascomycota are the two predominant fungal phyla, but Batch 1 harbored a notably high abundance of Basidiomycota and Batch 2 harbored a high abundance of Ascomycota. Moreover, the two batches harbored completely different fungal compositions and core fungal genera. FUNGuild (Fungal Functional Guild) analysis revealed that most of the fungal species present in the GIT are saprotroph, plant pathogen, and animal endosymbiont. Our study is the first to report that even under the same condition, large variations in fungal composition in the host GIT still occur from batch-to-batch and sampling time. The implications of our observations serve as references to the development of better models of the human gut.
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Evidence-Based and Emerging Diet Recommendations for Small Bowel Disorders. Am J Gastroenterol 2022; 117:958-964. [PMID: 35404303 PMCID: PMC9169759 DOI: 10.14309/ajg.0000000000001764] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 04/01/2022] [Indexed: 02/06/2023]
Abstract
Diet plays a key role in the manifestation and severity of gastrointestinal symptoms, with increasing research interest on the role of diet in small bowel disorders. There are predominantly 3 small bowel conditions that have potential dietary interventions. Self-reported nonceliac gluten/wheat sensitivity is prevalent. Although gluten is believed to be a potential trigger for symptoms, other components of wheat may also be triggers, including fructans, alpha-amylase trypsin inhibitors, and wheat germ agglutinins. The diagnosis can be challenging, given the lack of validated biomarkers. A gluten-free diet that excludes the abovementioned triggers is the cornerstone of treatment; however, unlike celiac disease, there is uncertainty about the level of adherence or whether the gluten-free diet is a lifelong intervention. Several primary gastrointestinal disorders are associated with an increase in inflammatory cells including eosinophils. Diet seems to be an important driver of disease pathogenesis in eosinophilic gastroenteritis, with elimination and elemental diets showing promise in management, with further robust trials required. Small intestinal bacterial overgrowth is an example of microbial dysbiosis, with renewed interest in diet being postulated to cause an adaptive change of the microbes colonizing the small intestine. However, the diagnosis of small intestinal bacterial overgrowth is limited by a lack of sensitive and specific tests, with significant knowledge gaps in relation to therapeutic measures to manage and cure small intestinal bacterial overgrowth. Currently, antimicrobials are the established management option. There have been significant clinical advances in dietary interventions related to the small bowel, but this area is currently a novel and advancing field for both patients and clinicians.
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14
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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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Shah A, Talley NJ, Holtmann G. Current and Future Approaches for Diagnosing Small Intestinal Dysbiosis in Patients With Symptoms of Functional Dyspepsia. Front Neurosci 2022; 16:830356. [PMID: 35600619 PMCID: PMC9121133 DOI: 10.3389/fnins.2022.830356] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 03/28/2022] [Indexed: 12/12/2022] Open
Abstract
The development and application of next generation sequencing technologies for clinical gastroenterology research has provided evidence that microbial dysbiosis is of relevance for the pathogenesis of gastrointestinal and extra-intestinal diseases. Microbial dysbiosis is characterized as alterations of diversity, function, and density of the intestinal microbes. Emerging evidence suggests that alterations of the gastrointestinal microbiome are important for the pathophysiology of a variety of functional gastrointestinal conditions, e.g., irritable bowel syndrome (IBS) and functional dyspepsia (FD), also known as disorders of brain-gut axis interaction. Clinicians have for many years recognized that small intestinal bacterial overgrowth (SIBO) is typified by a microbial dysbiosis that is underpinned by abnormal bacterial loads in these sites. SIBO presents with symptoms which overlap with symptoms of FD and IBS, point toward the possibility that SIBO is either the cause or the consequence of functional gastrointestinal disorders (FGIDs). More recently, new terms including "intestinal methanogen overgrowth" and "small intestinal fungal overgrowth" have been introduced to emphasize the contribution of methane production by archea and fungi in small intestinal dysbiosis. There is emerging data that targeted antimicrobial treatment of SIBO in patients with FD who simultaneously may or may not have IBS, results in symptom improvement and normalization of positive breath tests. However, the association between SIBO and FGIDs remains controversial, since widely accepted diagnostic tests for SIBO are lacking. Culture of jejunal fluid aspirate has been proposed as the "traditional gold standard" for establishing the diagnosis of SIBO. Utilizing jejunal fluid culture, the results can potentially be affected by cross contamination from oropharyngeal and luminal microbes, and there is controversy regarding the best cut off values for SIBO diagnosis. Thus, it is rarely used in routine clinical settings. These limitations have led to the development of breath tests, which when compared with the "traditional gold standard," have sub-optimal sensitivity and specificity for SIBO diagnosis. With newer diagnostic approaches-based upon applications of the molecular techniques there is an opportunity to characterize the duodenal and colonic mucosa associated microbiome and associated gut microbiota dysbiosis in patients with various gastrointestinal and extraintestinal diseases. Furthermore, the role of confounders like psychological co-morbidities, medications, dietary practices, and environmental factors on the gastrointestinal microbiome in health and disease also needs to be explored.
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Affiliation(s)
- Ayesha Shah
- Faculty of Medicine and Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- AGIRA (Australian Gastrointestinal Research Alliance) and the NHMRC Centre of Research Excellence in Digestive Health, Newcastle, NSW, Australia
| | - Nicholas J. Talley
- AGIRA (Australian Gastrointestinal Research Alliance) and the NHMRC Centre of Research Excellence in Digestive Health, Newcastle, NSW, Australia
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
| | - Gerald Holtmann
- Faculty of Medicine and Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- AGIRA (Australian Gastrointestinal Research Alliance) and the NHMRC Centre of Research Excellence in Digestive Health, Newcastle, NSW, Australia
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Gehlhaar A, Inala A, Llivichuzhca-Loja D, Silva TN, Adegboye CY, O’Connell AE, Konnikova L. Insights into the Role of Commensal-Specific T Cells in Intestinal Inflammation. J Inflamm Res 2022; 15:1873-1887. [PMID: 35342295 PMCID: PMC8943607 DOI: 10.2147/jir.s288288] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 02/19/2022] [Indexed: 12/21/2022] Open
Abstract
Trillions of microorganisms exist in the human intestine as commensals and contribute to homeostasis through their interactions with the immune system. In this review, we use previous evidence from published papers to elucidate the involvement of commensal-specific T cells (CSTCs) in regulating intestinal inflammatory responses. CSTCs are generated centrally in the thymus or peripherally at mucosal interfaces and present as CD4+ or CD8+ T cells. Bacteria, fungi, and even viruses act commensally with humans, warranting consideration of CSTCs in this critical relationship. Dysregulation of this immunological balance can result in both intestinal inflammation or damaging autoimmune responses elsewhere in the body. Given the relative novelty of CSTCs in the literature, we aim to introduce the importance of their role in maintaining immune homeostasis at barrier sites such as the intestine.
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Affiliation(s)
- Arne Gehlhaar
- Department of Pediatrics, Yale University, New Haven, CT, USA
| | - Ashwin Inala
- Department of Pediatrics, Yale University, New Haven, CT, USA
| | | | - Tatiana N Silva
- Department of Pediatrics, Yale University, New Haven, CT, USA
| | - Comfort Y Adegboye
- Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA
| | - Amy E O’Connell
- Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Liza Konnikova
- Department of Pediatrics, Yale University, New Haven, CT, USA
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, CT, USA
- Program in Human and Translational Immunology, Yale University, New Haven, CT, USA
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17
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Wang T, Dong J, Zhang G. Analyzing efficacy and safety of anti-fungal blue light therapy via kernel-based modeling the reactive oxygen species induced by light. IEEE Trans Biomed Eng 2022; 69:2433-2442. [PMID: 35085070 DOI: 10.1109/tbme.2022.3146567] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
OBJECTIVE The goal of this study is to investigate the efficacy, safety, and mechanism of ABL for inactivating Candida albicans (C. albicans), and to determine the best wavelength for treating candida infected disease, by experimental measurements and dynamic modeling. METHODS The changes in reactive oxygen species (ROS) in C. albicans and human host cells under the irradiation of 385, 405, and 415nm wavelengths light with irradiance of 50mW/cm2 were measured. Moreover, a kernel-based nonlinear dynamic model, i.e., nonlinear autoregressive with exogenous inputs (NARX), was developed and applied to predict the concentration of light-induced ROS, whose kernels were selected by a newly developed algorithm based on particle swarm optimization (PSO). RESULTS The ROS concentration was increased respectively about 10-12 times in C. albicans and about 3-6 times in human epithelial cells by the ABL treatment with the same fluence of 90J/cm2. The NARX models were respectively fitted to the data from the experiments on both types of cells. Besides, four different kernel functions, including Gaussian, Laplace, linear and polynomial kernels, were compared in their fitting accuracies. The errors with the Laplace kernel turned out to be only 0.2704 and 0.0593, as respectively fitted to the experimental data of the C. albicans and human host cells. CONCLUSION The results demonstrated the effectiveness of the NARX modeling approach, and revealed that the 415nm light was more effective as an anti-fungal treatment with less damage to the host cells than the 405 or 385nm light. SIGNIFICANCE The kernel-based NARX model identification algorithm offers opportunities for determining the effective and safe light dosages in treating various fungal infection diseases.
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Herman A, Herman AP. Could Candida Overgrowth Be Involved in the Pathophysiology of Autism? J Clin Med 2022; 11:442. [PMID: 35054136 PMCID: PMC8778531 DOI: 10.3390/jcm11020442] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 12/31/2021] [Accepted: 01/13/2022] [Indexed: 02/05/2023] Open
Abstract
The purpose of this review is to summarize the current acquiredknowledge of Candida overgrowth in the intestine as a possible etiology of autism spectrum disorder (ASD). The influence of Candida sp. on the immune system, brain, and behavior of children with ASD isdescribed. The benefits of interventions such as a carbohydrates-exclusion diet, probiotic supplementation, antifungal agents, fecal microbiota transplantation (FMT), and microbiota transfer therapy (MTT) will be also discussed. Our literature query showed that the results of most studies do not fully support the hypothesis that Candida overgrowth is correlated with gastrointestinal (GI) problems and contributes to autism behavioral symptoms occurrence. On the one hand, it was reported that the modulation of microbiota composition in the gut may decrease Candida overgrowth, help reduce GI problems and autism symptoms. On the other hand, studies on humans suggesting the beneficial effects of a sugar-free diet, probiotic supplementation, FMT and MTT treatment in ASD are limited and inconclusive. Due to the increasing prevalence of ASD, studies on the etiology of this disorder are extremely needed and valuable. However, to elucidate the possible involvement of Candida in the pathophysiology of ASD, more reliable and well-designed research is certainly required.
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Affiliation(s)
- Anna Herman
- Faculty of Health Sciences, Warsaw School of Engineering and Health, Bitwy Warszawskiej 20 18, 19 Street, 02-366 Warsaw, Poland
| | - Andrzej Przemysław Herman
- Department of Genetic Engineering, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 Street, 05-110 Jabłonna, Poland;
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Vavreckova M, Galanova N, Kostovcik M, Krystynik O, Ivanovova E, Roubalova R, Jiraskova Zakostelska Z, Friedecky D, Friedecka J, Haluzik M, Karasek D, Kostovcikova K. Specific gut bacterial and fungal microbiota pattern in the first half of pregnancy is linked to the development of gestational diabetes mellitus in the cohort including obese women. Front Endocrinol (Lausanne) 2022; 13:970825. [PMID: 36133313 PMCID: PMC9484836 DOI: 10.3389/fendo.2022.970825] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 08/15/2022] [Indexed: 11/30/2022] Open
Abstract
AIMS Gestation is linked to changes in gut microbiota composition and function. Since gestational diabetes mellitus (GDM) can develop at any time of the pregnancy, we stratified the women into four groups according to the time and test used for the diagnosis. We focused on the gut microbiota pattern in early pregnancy to detect changes which could be linked to later GDM development. METHODS We collected stool samples from 104 pregnant women including obese individuals (first trimester body mass index median was 26.73). We divided the women into four groups according to routine screening of fasting plasma glucose (FPG) levels and oral glucose tolerance test (oGTT) in the first and third trimesters, respectively. We processed the stool samples for bacterial 16S rRNA and fungal ITS1 genes sequencing by Illumina MiSeq approach and correlated the gut microbiota composition with plasma short-chain fatty acid levels (SCFA). RESULTS We found that gut bacterial microbiota in the first trimester significantly differs among groups with different GDM onset based on unweighted UniFrac distances (p=0.003). Normoglycemic women had gut microbiota associated with higher abundance of family Prevotellaceae, and order Fusobacteriales, and genus Sutterella. Women diagnosed later during pregnancy either by FGP levels or by oGTT had higher abundances of genera Enterococcus, or Erysipelotrichaceae UCG-003, respectively. We observed significant enrichment of fungal genus Mucor in healthy pregnant women whereas Candida was more abundant in the group of pregnant women with impaired oGTT. Using correlation analysis, we found that Holdemanella negatively correlated with Blautia and Candida abundances and that Escherichia/Shigella abundance positively correlated and Subdoligranulum negatively correlated with plasma lipid levels. Coprococcus, Akkermansia, Methanobrevibacter, Phascolarctobacterium and Alistipes positively correlated with acetate, valerate, 2-hydroxybutyrate and 2-methylbutyrate levels, respectively, in women with GDM. CONCLUSIONS We conclude that there are significant differences in the gut microbiota composition between pregnant women with and without GDM already at the early stage of pregnancy in our cohort that included also overweight and obese individuals. Specific microbial pattern associated with GDM development during early pregnancy and its correlation to plasma lipid or SCFA levels could help to identify women in higher risk of GDM development.
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Affiliation(s)
- Marketa Vavreckova
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Natalie Galanova
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Martin Kostovcik
- Laboratory of Fungal Genetics and Metabolism, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Ondrej Krystynik
- Third Department of Internal Medicine – Nephrology, Rheumatology and Endocrinology, University Hospital Olomouc, Olomouc, Czechia
| | - Eliska Ivanovova
- Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc, and Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czechia
| | - Radka Roubalova
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - Zuzana Jiraskova Zakostelska
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
| | - David Friedecky
- Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc, and Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czechia
| | - Jaroslava Friedecka
- Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc, and Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czechia
| | - Martin Haluzik
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czechia
| | - David Karasek
- Third Department of Internal Medicine – Nephrology, Rheumatology and Endocrinology, University Hospital Olomouc, Olomouc, Czechia
| | - Klara Kostovcikova
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
- *Correspondence: Klara Kostovcikova,
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20
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Brown H, Esterházy D. Intestinal immune compartmentalization: implications of tissue specific determinants in health and disease. Mucosal Immunol 2021; 14:1259-1270. [PMID: 34211125 DOI: 10.1038/s41385-021-00420-8] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 05/05/2021] [Accepted: 05/24/2021] [Indexed: 02/04/2023]
Abstract
The emerging concept of tissue specific immunity has opened the gates to new inquiries into what factors drive immune cell niche adaptation and the implications on immune homeostasis, organ specific immune diseases, and therapeutic efficacy. These issues are particularly complicated at barrier sites, which are directly exposed to an ever-changing environment. In particular, the gastrointestinal (GI) tract faces even further challenges given the profound functional and structural differences along its length, raising the possibility that it may even have to be treated as multiple organs when seeking to answer these questions. In this review, we evaluate what is known about the tissue intrinsic and extrinsic factors shaping immune compartments in the intestine. We then discuss the physiological and pathological consequences of a regionally distinct immune system in a single organ, but also discuss where our insight into the role of the compartment for disease development is still very limited. Finally, we discuss the technological and therapeutic implications this compartmentalization has. While the gut is perhaps one of the most intensely studied systems, many of these aspects apply to understanding tissue specific immunity of other organs, most notably other barrier sites such as skin, lung, and the urogenital tract.
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Affiliation(s)
- Hailey Brown
- Committee on Immunology, University of Chicago, Chicago, IL, USA
| | - Daria Esterházy
- Committee on Immunology, University of Chicago, Chicago, IL, USA. .,Department of Pathology, University of Chicago, Chicago, IL, USA.
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21
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Ashley BK, Hassan U. Point-of-critical-care diagnostics for sepsis enabled by multiplexed micro and nanosensing technologies. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2021; 13:e1701. [PMID: 33650293 PMCID: PMC8447248 DOI: 10.1002/wnan.1701] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 12/14/2020] [Accepted: 01/08/2021] [Indexed: 11/12/2022]
Abstract
Sepsis is responsible for the highest economic and mortality burden in critical care settings around the world, prompting the World Health Organization in 2018 to designate it as a global health priority. Despite its high universal prevalence and mortality rate, a disproportionately low amount of sponsored research funding is directed toward diagnosis and treatment of sepsis, when early treatment has been shown to significantly improve survival. Additionally, current technologies and methods are inadequate to provide an accurate and timely diagnosis of septic patients in multiple clinical environments. For improved patient outcomes, a comprehensive immunological evaluation is critical which is comprised of both traditional testing and quantifying recently proposed biomarkers for sepsis. There is an urgent need to develop novel point-of-care, low-cost systems which can accurately stratify patients. These point-of-critical-care sensors should adopt a multiplexed approach utilizing multimodal sensing for heterogenous biomarker detection. For effective multiplexing, the sensors must satisfy criteria including rapid sample to result delivery, low sample volumes for clinical sample sparring, and reduced costs per test. A compendium of currently developed multiplexed micro and nano (M/N)-based diagnostic technologies for potential applications toward sepsis are presented. We have also explored the various biomarkers targeted for sepsis including immune cell morphology changes, circulating proteins, small molecules, and presence of infectious pathogens. An overview of different M/N detection mechanisms are also provided, along with recent advances in related nanotechnologies which have shown improved patient outcomes and perspectives on what future successful technologies may encompass. This article is categorized under: Diagnostic Tools > Biosensing.
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Affiliation(s)
- Brandon K. Ashley
- Department of Biomedical Engineering, Rutgers, State University of New Jersey, Piscataway, NJ, 08854, USA
| | - Umer Hassan
- Department of Biomedical Engineering, Rutgers, State University of New Jersey, Piscataway, NJ, 08854, USA
- Department of Electrical Engineering, Rutgers, State University of New Jersey, Piscataway, NJ, 08854, USA
- Global Health Institute, Rutgers, State University of New Jersey. Piscataway, NJ, 08854, USA
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22
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Dwivedi M, Powali S, Rastogi S, Singh A, Gupta DK. Microbial community in human gut: a therapeutic prospect and implication in health and diseases. Lett Appl Microbiol 2021; 73:553-568. [PMID: 34365651 DOI: 10.1111/lam.13549] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 07/30/2021] [Accepted: 08/03/2021] [Indexed: 12/14/2022]
Abstract
The interest in the working and functionality of the human gut microbiome has increased drastically over the years. Though the existence of gut microbes has long been speculated for long over the last few decades, a lot of research has sprung up in studying and understanding the role of gut microbes in the human digestive tract. The microbes present in the gut are highly instrumental in maintaining the metabolism in the body. Further research is going on in this field to understand how gut microbes can be employed as potential sources of novel therapeutics; moreover, probiotics have also elucidated their significant place in this direction. As regards the clinical perspective, microbes can be engineered to afford defence mechanisms while interacting with foreign pathogenic bodies. More investigations in this field may assist us to evaluate and understand how these cells communicate with human cells and promote immune interactions. Here we elaborate on the possible implication of human gut microbiota into the immune system as well as explore the probiotics in the various human ailments. Comprehensive information on the human gut microbiome at the same platform may contribute effectively to our understanding of the human microbiome and possible mechanisms of associated human diseases.
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Affiliation(s)
- M Dwivedi
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow, India
| | - S Powali
- Maulana Abdul Kalam Azad University of Technology, Kolkatta, India
| | - S Rastogi
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow, India
| | - A Singh
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow, India
| | - D K Gupta
- Department of Biochemistry, University of Allahabad, Prayagraj, India
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23
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Musumeci S, Coen M, Leidi A, Schrenzel J. The human gut mycobiome and the specific role of Candida albicans: where do we stand, as clinicians? Clin Microbiol Infect 2021; 28:58-63. [PMID: 34363944 DOI: 10.1016/j.cmi.2021.07.034] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/08/2021] [Accepted: 07/22/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND The so-called 'mycobiome' has progressively acquired interest and increased the complexity of our understanding of the human gut microbiota. Several questions are arising concerning the role of fungi (and in particular of Candida albicans), the so-called 'mycobiome', that has been neglected for a long time and only recently gained interest within the scientific community. There is no consensus on mycobiome normobiosis because of its instability and variability. This review aims to raise awareness about this interesting topic and provide a framework to guide physicians faced with such questions. OBJECTIVES To summarize current knowledge and discuss current and potential implications of the mycobiome in clinical practice. SOURCES We performed a review of the existing literature in Medline Pubmed. CONTENT This review identifies several studies showing associations between specific mycobiome profiles and health. Fungi represent a significant biomass within the microbiota and several factors, such as diet, sex, age, co-morbidities, medications, immune status and inter-kingdom interactions, can influence its structure and population. The human gut mycobiota is indeed a key factor for several physiological processes (e.g. training of the immune system against infections) and pathological processes (e.g. immunological/inflammatory disorders, inflammatory bowel diseases, metabolic syndromes). Moreover, the mycobiome (and C. albicans in particular) could influence an even broader spectrum of conditions such as psychiatric diseases (depression, schizophrenia, bipolar disorder) or chronic viral infections (human immunodeficiency virus, hepatitis B virus); moreover, it could be implicated in tumorigenesis. IMPLICATIONS Candida albicans is a well-known opportunistic pathogen and a major component of the mycobiome but its role in the gastrointestinal tract is still poorly understood. From a potential screening biomarker to a key factor for several pathological processes, its presence could influence or even modify our clinical practice.
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Affiliation(s)
- Stefano Musumeci
- Service of Internal Medicine, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Matteo Coen
- Service of Internal Medicine, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland; Unit of Development and Research in Medical Education (UDREM), Faculty of Medicine, Geneva, Switzerland.
| | - Antonio Leidi
- Service of Internal Medicine, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Jacques Schrenzel
- Bacteriology Laboratory, Department of Diagnostics, Geneva University Hospitals, Geneva, Switzerland; Genomic Research Laboratory, Department of Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland; Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland
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24
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Ahmad F, Farooq A, Khan MUG. Deep Learning Model for Pathogen Classification Using Feature Fusion and Data Augmentation. Curr Bioinform 2021. [DOI: 10.2174/1574893615999200707143535] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Bacterial pathogens are deadly for animals and humans. The ease of their dissemination, coupled
with their high capacity for ailment and death in infected individuals, makes them a threat to society.
Objective:
Due to high similarity among genera and species of pathogens, it is sometimes difficult for microbiologists to
differentiate between them. Their automatic classification using deep-learning models can help in reliable, and accurate
outcomes.
Method:
Deep-learning models, namely; AlexNet, GoogleNet, ResNet101, and InceptionV3 are used with numerous
variations including training model from scratch, fine-tuning without pre-trained weights, fine-tuning along with freezing
weights of initial layers, fine-tuning along with adjusting weights of all layers and augmenting the dataset by random
translation and reflection. Moreover, as the dataset is small, fine-tuning and data augmentation strategies are applied to
avoid overfitting and produce a generalized model. A merged feature vector is produced using two best-performing models
and accuracy is calculated by xgboost algorithm on the feature vector by applying cross-validation.
Results:
Fine-tuned models where augmentation is applied produces the best results. Out of these, two-best-performing
deep models i.e. (ResNet101, and InceptionV3) selected for feature fusion, produced a similar validation accuracy of 95.83
with a loss of 0.0213 and 0.1066, and a testing accuracy of 97.92 and 93.75, respectively. The proposed model used xgboost
to attained a classification accuracy of 98.17% by using 35-folds cross-validation.
Conclusion:
The automatic classification using these models can help experts in the correct identification of pathogens.
Consequently, they can help in controlling epidemics and thereby minimizing the socio-economic impact on the community.
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Affiliation(s)
- Fareed Ahmad
- Department of Computer Science and Engineering, Faculty of Electrical Engineering, University of Engineering and Technology, Lahore, Pakistan
| | - Amjad Farooq
- Department of Computer Science and Engineering, Faculty of Electrical Engineering, University of Engineering and Technology, Lahore, Pakistan
| | - Muhammad Usman Ghani Khan
- Department of Computer Science and Engineering, Faculty of Electrical Engineering, University of Engineering and Technology, Lahore, Pakistan
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25
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Kim H, Lee DG. Naringin-generated ROS promotes mitochondria-mediated apoptosis in Candida albicans. IUBMB Life 2021; 73:953-967. [PMID: 33934490 DOI: 10.1002/iub.2476] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/01/2021] [Accepted: 04/15/2021] [Indexed: 12/06/2022]
Abstract
Naringin is a flavonoid which has a therapeutic effect. However, the details of its antifungal mechanism have not yet been fully elucidated. This study focused on clarifying the relationship between naringin and Candida albicans, to understand its mode of antifungal action. In general, naringin is an antioxidant, but our results indicated that 1 mM naringin generates intracellular superoxide (O2 - ) and hydroxyl radicals (OH- ). Reactive oxygen species (ROS) have a serious impact on Ca2+ signaling and the production of mitochondrial ROS. After exposure to enhanced O2 - and OH- , mitochondrial Ca2+ overload and mitochondrial O2 - generation were confirmed in C. albicans. It was verified that mitochondrial O2 - transforms mitochondrial glutathione (GSH) to oxidized GSH (GSSG), leading to extreme oxidative stress in mitochondria. The previously observed Ca2+ accumulation and oxidative stress resulted in mitochondrial membrane potential (MMP) alteration and increased mitochondrial mass. In succession, cytochrome c release from the mitochondria to the cytosol was detected due to MMP loss. Cytochrome c promotes the initiation of apoptosis, and further experiments were performed to assess the apoptotic hallmarks. Metacaspases activation, chromosomal condensation, DNA fragmentation, and phosphatidylserine exposure were observed, indicating that naringin induces apoptosis in C. albicans. In conclusion, our findings manifested that naringin-generated O2 - and OH- damage the mitochondria and that mitochondrial dysfunction-mediated apoptosis is novel antifungal mechanism of naringin.
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Affiliation(s)
- Heesu Kim
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, South Korea
| | - Dong Gun Lee
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, South Korea
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Al-Jameel SS. Association of diabetes and microbiota: An update. Saudi J Biol Sci 2021; 28:4446-4454. [PMID: 34354429 PMCID: PMC8324937 DOI: 10.1016/j.sjbs.2021.04.041] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/15/2021] [Accepted: 04/17/2021] [Indexed: 12/19/2022] Open
Abstract
Diabetes is an emerging health condition globally and is suggested to have a direct connection with the gut microbiota that determine our metabolic outcomes. Sensitivity to insulin and glucose metabolism is normal in healthy people as compared to those people who cannot maintain their glucose metabolism. One of the reasons of the differences is that healthy people have different microbiome that leads to achieve more short chain fatty acids and make up more branched amino acids, while the gut microbiota of the other group of people are more likely to produce compounds that affects glucose metabolism. Herein, this review will present the research related to the impact of gut microbes on diabetes carried out in the past decade. The review focus on the relation between gut microbiota and Type-1 Diabetes (T1D), Type-2 Diabetes (T2D), and how gut microbiota could be an alternative therapy for treatment of diabetes.
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Affiliation(s)
- Suhailah S Al-Jameel
- Department of Chemistry, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
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Yang T, Chakraborty S, Mandal J, Mei X, Joe B. Microbiota and Metabolites as Factors Influencing Blood Pressure Regulation. Compr Physiol 2021; 11:1731-1757. [PMID: 33792901 DOI: 10.1002/cphy.c200009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The study of microbes has rapidly expanded in recent years due to a surge in our understanding that humans host a plethora of commensal microbes, which reside in their bodies and depending upon their composition, contribute to either normal physiology or pathophysiology. This article provides a general foundation for learning about host-commensal microbial interactions as an emerging area of research. The article is divided into two sections. The first section is dedicated to introducing commensal microbiota and its known effects on the host. The second section is on metabolites, which are biochemicals that the host and the microbes use for bi-directional communication with each other. Together, the sections review what is known about how microbes interact with the host to impact cardiovascular physiology, especially blood pressure regulation. © 2021 American Physiological Society. Compr Physiol 11:1731-1757, 2021.
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Affiliation(s)
- Tao Yang
- Center for Hypertension and Precision Medicine and Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA
| | - Saroj Chakraborty
- Center for Hypertension and Precision Medicine and Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA
| | - Juthika Mandal
- Center for Hypertension and Precision Medicine and Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA
| | - Xue Mei
- Center for Hypertension and Precision Medicine and Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA
| | - Bina Joe
- Center for Hypertension and Precision Medicine and Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA
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Banerjee A, Pradhan LK, Sahoo PK, Jena KK, Chauhan NR, Chauhan S, Das SK. Unravelling the potential of gut microbiota in sustaining brain health and their current prospective towards development of neurotherapeutics. Arch Microbiol 2021; 203:2895-2910. [PMID: 33763767 DOI: 10.1007/s00203-021-02276-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 02/18/2021] [Accepted: 03/10/2021] [Indexed: 12/12/2022]
Abstract
Increasing incidences of neurological disorders, such as Parkinson's disease (PD), multiple sclerosis (MS), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are being reported, but an insight into their pathology remains elusive. Findings have suggested that gut microbiota play a major role in regulating brain functions through the gut-brain axis. A unique bidirectional communication between gut microbiota and maintenance of brain health could play a pivotal role in regulating incidences of neurodegenerative diseases. Contrarily, the present life style with changing food habits and disturbed circadian rhythm may contribute to gut homeostatic imbalance and dysbiosis leading to progression of several neurological disorders. Therefore, dysbiosis, as a primary factor behind intestinal disorders, may also augment inflammation, intestinal and blood-brain barrier permeability through microbiota-gut-brain axis. This review primarily focuses on the gut-brain axis functions, specific gut microbial population, metabolites produced by gut microbiota, their role in regulating various metabolic processes and role of gut microbiota towards development of neurodegenerative diseases. However, several studies have reported a decrease in abundance of a specific gut microbial population and a corresponding increase in other microbial family, with few findings revealing some contradictions. Reports also showed that colonization of gut microbiota isolated from patients suffering from neurodegenerative disease leads to the development of enhance pathological outcomes in animal models. Hence, a systematic understanding of the dominant role of specific gut microbiome towards development of different neurodegenerative diseases could possibly provide novel insight into the use of probiotics and microbial transplantation as a substitute approach for treating/preventing such health maladies.
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Affiliation(s)
- Ankita Banerjee
- Neurobiology Laboratory, Centre for Biotechnology, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, 751003, Odisha, India
| | - Lilesh Kumar Pradhan
- Neurobiology Laboratory, Centre for Biotechnology, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, 751003, Odisha, India
| | - Pradyumna Kumar Sahoo
- Neurobiology Laboratory, Centre for Biotechnology, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, 751003, Odisha, India
| | - Kautilya Kumar Jena
- Autophagy Laboratory, Infectious Disease Biology Division, Institute of Life Sciences, Bhubaneswar, 751023, Odisha, India
| | - Nishant Ranjan Chauhan
- Autophagy Laboratory, Infectious Disease Biology Division, Institute of Life Sciences, Bhubaneswar, 751023, Odisha, India
| | - Santosh Chauhan
- Autophagy Laboratory, Infectious Disease Biology Division, Institute of Life Sciences, Bhubaneswar, 751023, Odisha, India
| | - Saroj Kumar Das
- Neurobiology Laboratory, Centre for Biotechnology, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, 751003, Odisha, India.
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Sabit H, Tombuloglu H, Rehman S, Almandil NB, Cevik E, Abdel-Ghany S, Rashwan S, Abasiyanik MF, Yee Waye MM. Gut microbiota metabolites in autistic children: An epigenetic perspective. Heliyon 2021; 7:e06105. [PMID: 33553761 PMCID: PMC7848646 DOI: 10.1016/j.heliyon.2021.e06105] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 01/18/2021] [Accepted: 01/22/2021] [Indexed: 12/18/2022] Open
Abstract
Gut microbiota has become an issue of great importance recently due to its major role in autism spectrum disorder (ASD). Over the past three decades, there has been a sustained research activity focused to explain the actual mechanism by which gut microbiota triggers/develops autism. Several genetic and epigenetic factors are involved in this disorder, with epigenetics being the most active area of research. Although the constant investigation and advancements, epigenetic implications in ASD still need a deeper functional/causal analysis. In this review, we describe the major gut microbiota metabolites and how they induce epigenetic changes in ASD along with interactions through the gut-brain axis.
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Affiliation(s)
- Hussein Sabit
- Department of Genetics, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P. O. Box 1982, Dammam, 31441 Saudi Arabia
| | - Huseyin Tombuloglu
- Department of Genetics, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P. O. Box 1982, Dammam, 31441 Saudi Arabia
| | - Suriya Rehman
- Department of Epidemic Diseases, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P. O. Box 1982, Dammam, 31441 Saudi Arabia
| | - Noor B Almandil
- Department of Clinical Pharmacy Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, P. O. Box 1982, Dammam, 31441 Saudi Arabia
| | - Emre Cevik
- Department of Genetics, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P. O. Box 1982, Dammam, 31441 Saudi Arabia
| | - Shaimaa Abdel-Ghany
- Department of Environmental Biotechnology, College of Biotechnology, Misr University for Science and Technology, P. O. Box 77, Giza, Egypt
| | - Sanaa Rashwan
- Pediatrics Department, Madinat Zayed Hospital, SEHA, Abu Dhabi, United Arab Emirates
| | - Mustafa Fatih Abasiyanik
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, USA.,Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL, 60637, USA
| | - Mary Miu Yee Waye
- The Nethersole School of Nursing, The Croucher Laboratory for Human Genomics, The Chinese University of Hong Kong, Shatin, N.T. Hong Kong
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Wang H, Li X, Wang D, Li C, Wang Y, Diao Y, Tang Y. Isolation, identification and genotyping of Candida albicans from Landes geese. Transbound Emerg Dis 2021; 69:349-359. [PMID: 33417748 DOI: 10.1111/tbed.13985] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 12/28/2020] [Accepted: 01/05/2021] [Indexed: 11/29/2022]
Abstract
In May 2018, Landes geese raised in Weifang, Shandong Province, China, developed a disease characterized by thickened oesophageal mucosa and white, round ulcers. Based on pathogen isolation and identification, differential culture and morphological observations, Candida albicans (C. albicans) was identified as the causative pathogen from the oesophagus of infected geese, and artificial infection experiments were then performed using the isolated strains. In experimental reproduction, the symptoms of infected geese were consistent with those of natural infection, and gosling morbidity and mortality were 75% and 60%, respectively. Re-isolation of the strain from the dead goslings confirmed C. albicans as the causative pathogen of oesophageal ulcers. We further performed internal transcribed space rDNA sequence analysis, ABC genotyping and multi-locus sequence typing analysis. We observed 100% sequence similarity between the two strains, designated as WFCL and WFLQ, which were isolated from different regions, with 100% homology between the strains isolated in the present study and the human-origin C. albicans strains isolated previously from China. The goose-origin strains isolated in this study and the human-origin C. albicans isolates were included in the same branch in phylogenetic trees analysis, indicating that the strain responsible for oesophageal ulcer in geese is closely related to human-origin C. albicans. In addition, based on eBURST analysis of sequence types, goose-origin C. albicans strains were relatively independent in terms of population evolution. To the best of our knowledge, this is the first detailed report on goose oesophageal ulceration caused by C. albicans infection in geese. Considering that C. albicans is an important zoonotic pathogen, this study provides a reference for further studies on avian C. albicans infections and is important for ensuring public health and safety.
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Affiliation(s)
- Hongzhi Wang
- College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, China
| | - Xudong Li
- College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, China
| | - Dongxue Wang
- College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, China
| | - Chong Li
- Hebei Provincial Center of Animal Disease Control and Prevention, Shijiazhuang, China
| | - Yuanyuan Wang
- China Animal Health and Epidemiology Center, Qingdao, China
| | - Youxiang Diao
- College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, China
| | - Yi Tang
- College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, China.,Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, China
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Smit B, Kuballa A, Coulson S, Katouli M. Interaction of Candida albicans with human gut epithelium in the presence of Live Biotherapeutic Products (LBPs). MICROBIOLOGY AUSTRALIA 2021. [DOI: 10.1071/ma21035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Candida albicans is a semi-ubiquitous pathobiont that is known to significantly impact human health and wellbeing, causing a significant financial strain on the medical system. Due to increasing antifungal resistance, there is a growing need for novel fungal therapeutics to treat diseases caused by this fungus. The development and use of Live Biotherapeutic Products (LBPs) is an innovative and novel approach to potentially treating Candidiasis and other comorbidities associated with C. albicans infection. To evaluate their anti-pathogenic efficacy, it is necessary to understand the underlying mechanisms involved, via the use of biomimetic cell models. In this study, six LBPs were chosen to investigate their competitive inhibitory effect against C. albicans using a co-culture of Caco-2 cells and mucous-secreting HT29-MTX cells to mimic human gut epithelium. The LBP strains were supplied by Servatus Biopharmaceuticals and identified as SVT 01D1, SVT 04P1, SVT 05P2, SVT 06B1, SVT 07R1 and SVT 08Z1. Five out of the six LBPs showed a significant reduction in the adhesion of C. albicans and all six LBPs reduced C. albicans invasion in the co-culture cells to varying degrees. There was no significant difference between co-inoculation of C. albicans with the LBPs or pre-inoculation of LBPs before the addition of C. albicans. The potential of these LBPs as novel anti-fungal therapeutics for the treatment of C. albicans diseases can be further documented in clinical trials.
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Zarnowski R, Jaromin A, Zagórska A, Dominguez EG, Sidoryk K, Gubernator J, Andes DR. A Label-Free Cellular Proteomics Approach to Decipher the Antifungal Action of DiMIQ, a Potent Indolo[2,3- b]Quinoline Agent, against Candida albicans Biofilms. Int J Mol Sci 2020; 22:ijms22010108. [PMID: 33374351 PMCID: PMC7795236 DOI: 10.3390/ijms22010108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 12/18/2020] [Accepted: 12/21/2020] [Indexed: 12/20/2022] Open
Abstract
Candida albicans forms extremely drug-resistant biofilms, which present a serious threat to public health globally. Biofilm-based infections are difficult to treat due to the lack of efficient antifungal therapeutics, resulting in an urgent demand for the development of novel antibiofilm strategies. In this study, the antibiofilm activity of DiMIQ (5,11-dimethyl-5H-indolo[2,3-b]quinoline) was evaluated against C. albicans biofilms. DiMIQ is a synthetic derivative of indoquinoline alkaloid neocryptolepine isolated from a medicinal African plant, Cryptolepis sanguinolenta. Antifungal activity of DiMIQ was determined using the XTT assay, followed by cell wall and extracellular matrix profiling and cellular proteomes. Here, we demonstrated that DiMIQ inhibited C. albicans biofilm formation and altered fungal cell walls and the extracellular matrix. Cellular proteomics revealed inhibitory action against numerous translation-involved ribosomal proteins, enzymes involved in general energy producing processes and select amino acid metabolic pathways including alanine, aspartate, glutamate, valine, leucine and isoleucine. DiMIQ also stimulated pathways of cellular oxidation, metabolism of carbohydrates, amino acids (glycine, serine, threonine, arginine, phenylalanine, tyrosine, tryptophan) and nucleic acids (aminoacyl-tRNA biosynthesis, RNA transport, nucleotide metabolism). Our findings suggest that DiMIQ inhibits C. albicans biofilms by arresting translation and multidirectional pathway reshaping of cellular metabolism. Overall, this agent may provide a potent alternative to treating biofilm-associated Candida infections.
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Affiliation(s)
- Robert Zarnowski
- Department of Medicine, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA; (E.G.D.); (D.R.A.)
- Department of Medical Microbiology, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA
- Correspondence: (R.Z.); (A.J.); Tel.: +1-608-265-8578 (R.Z.); +48-71-375-6203 (A.J.)
| | - Anna Jaromin
- Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland;
- Correspondence: (R.Z.); (A.J.); Tel.: +1-608-265-8578 (R.Z.); +48-71-375-6203 (A.J.)
| | - Agnieszka Zagórska
- Department of Medicinal Chemistry, Jagiellonian University Medical College, 30-688 Cracow, Poland;
| | - Eddie G. Dominguez
- Department of Medicine, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA; (E.G.D.); (D.R.A.)
- Department of Medical Microbiology, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA
| | - Katarzyna Sidoryk
- Department of Pharmacy, Cosmetic Chemicals and Biotechnology, Team of Chemistry, Łukasiewicz Research Network-Industrial Chemistry Institute, 01-793 Warsaw, Poland;
| | - Jerzy Gubernator
- Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland;
| | - David R. Andes
- Department of Medicine, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA; (E.G.D.); (D.R.A.)
- Department of Medical Microbiology, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA
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Natural Preparations Based on Orange, Bergamot and Clove Essential Oils and Their Chemical Compounds as Antimicrobial Agents. Molecules 2020; 25:molecules25235502. [PMID: 33255327 PMCID: PMC7727698 DOI: 10.3390/molecules25235502] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 11/16/2020] [Accepted: 11/20/2020] [Indexed: 12/15/2022] Open
Abstract
Since ancient times complementary therapies have been based on the use of medicinal plants, natural preparations and essential oils in the treatment of various diseases. Their use in medical practice is recommended in view of their low toxicity, pharmacological properties and economic impact. This paper aims to test the antimicrobial effect of natural preparation based on clove, orange and bergamot essential oils on a wide range of microorganisms that cause infections in humans including: Streptococcus pyogenes, Staphylococcus aureus, Shigella flexneri, Candida parapsilosis, Candida albicans, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhimurium and Haemophilus influenza. Three natural preparations such as one-component emulsions: clove (ECEO), bergamote (EBEO), and orange (EOEO), three binary: E(BEO/CEO), E(BEO/OEO), E(CEO/OEO) and a tertiary emulsion E(OEO/BEO/CEO) were obtained, characterized and tested for antimicrobial effects. Also, the synergistic/antagonistic effects, generated by the presence of the main chemical compounds, were studied in order to recommend a preparation with optimal antimicrobial activity. The obtained results underline the fact that the monocomponent emulsion ECEO shows antimicrobial activity, while EOEO and EBEO do not inhibit the development of the analyzed strains. In binary or tertiary emulsions E(BEO/CEO), E(CEO/OEO) and E(OEO/ BEO/CEO) the antimicrobial effect of clove oil is potentiated due to the synergism exerted by the chemical compounds of essential oils.
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Chronic diarrhoea in an oncology patient - Clinical assessment and decision making. Best Pract Res Clin Gastroenterol 2020; 48-49:101708. [PMID: 33317791 DOI: 10.1016/j.bpg.2020.101708] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 10/21/2020] [Accepted: 11/05/2020] [Indexed: 01/31/2023]
Abstract
Cancer survival is improving rapidly due to advances in treatments that will often involve radiotherapy, chemotherapy and novel biological agents in addition to surgery. This comes at the price of living with chronic symptoms, of which diarrhoea is particularly common. There is good evidence that for many patients these symptoms become part of everyday life, their "normality" is adjusted and symptoms are tolerated even when limiting activities severely. Clinicians often fail to appreciate the impact of these problems, as the focus of follow up tends to be on cancer recurrence. However, the rapid identification of patients in significant trouble can lead to earlier diagnosis of treatable pathologies and improvement of patients' symptoms. The aim of this review is to highlight the mechanisms which cause oncology patients to develop diarrhoea and highlight useful investigational and treatment strategies.
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Abstract
Small intestinal bacterial overgrowth (SIBO) is a common, yet underrecognized, problem. Its prevalence is unknown because SIBO requires diagnostic testing. Although abdominal bloating, gas, distension, and diarrhea are common symptoms, they do not predict positive diagnosis. Predisposing factors include proton-pump inhibitors, opioids, gastric bypass, colectomy, and dysmotility. Small bowel aspirate/culture with growth of 10-10 cfu/mL is generally accepted as the "best diagnostic method," but it is invasive. Glucose or lactulose breath testing is noninvasive but an indirect method that requires further standardization and validation for SIBO. Treatment, usually with antibiotics, aims to provide symptom relief through eradication of bacteria in the small intestine. Limited numbers of controlled studies have shown systemic antibiotics (norfloxacin and metronidazole) to be efficacious. However, 15 studies have shown rifaximin, a nonsystemic antibiotic, to be effective against SIBO and well tolerated. Through improved awareness and scientific rigor, the SIBO landscape is poised for transformation.
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Lema I, Araújo JR, Rolhion N, Demignot S. Jejunum: The understudied meeting place of dietary lipids and the microbiota. Biochimie 2020; 178:124-136. [PMID: 32949677 DOI: 10.1016/j.biochi.2020.09.007] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 09/08/2020] [Accepted: 09/09/2020] [Indexed: 12/12/2022]
Abstract
Although the jejunum is the main intestinal compartment responsible for lipid digestion and absorption, most of the studies assessing the impact of dietary lipids on the intestinal microbiota have been performed in the ileum, colon and faeces. This lack of interest in the jejunum is due to the much lower number of microbes present in this intestinal region and to the difficulty in accessing its lumen, which requires invasive methods. Recently, several recent publications highlighted that the whole jejunal microbiota or specific bacterial members are able to modulate lipid absorption and metabolism in enterocytes. This information reveals new strategies in the development of bacterial- and metabolite-based therapeutic interventions or nutraceutical recommendations to treat or prevent metabolic-related disorders, including obesity, cardiovascular diseases and malnutrition. This review is strictly focused on the following triad: dietary lipids, the jejunal epithelium and the jejunal microbiota. First, we will describe each member of the triad: the structure and functions of the jejunum, the composition of the jejunal microbiota, and dietary lipid handling by enterocytes and by microorganisms. Then, we will present the mechanisms leading to lipid malabsorption in small intestinal bacterial overgrowth (SIBO), a disease in which the jejunal microbiota is altered and which highlights the strong interactions among this triad. We will finally review the recent literature about the interactions among members of the triad, which should encourage research teams to further explore the mechanisms by which specific microbial strains or metabolites, alone or in concert, can mediate, control or modulate lipid absorption in the jejunum.
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Affiliation(s)
- Ingrid Lema
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, UMR_S 938, F-75012, Paris, France; EPHE, PSL University, F-75014, Paris, France
| | - João Ricardo Araújo
- Nutrition and Metabolism, NOVA Medical School, NOVA University of Lisbon, Lisbon, Portugal; Center for Health Technology Services Research (CINTESIS), Oporto, Portugal
| | - Nathalie Rolhion
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, UMR_S 938, F-75012, Paris, France
| | - Sylvie Demignot
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, UMR_S 938, F-75012, Paris, France; EPHE, PSL University, F-75014, Paris, France.
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The duodenal microbiome is altered in small intestinal bacterial overgrowth. PLoS One 2020; 15:e0234906. [PMID: 32645011 PMCID: PMC7347122 DOI: 10.1371/journal.pone.0234906] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 06/04/2020] [Indexed: 12/14/2022] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is highly prevalent and is associated with numerous gastrointestinal disorders, but the microbes involved remain poorly defined. Moreover, existing studies of microbiome alterations in SIBO have utilized stool samples, which are not representative of the entire gastrointestinal tract. Therefore, we aimed to determine and compare the duodenal microbiome composition in SIBO and non-SIBO subjects, using duodenal aspirates from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Using the recently-redefined cutoff for SIBO of >103 colony forming units per milliliter (CFU/mL), 42 SIBO and 98 non-SIBO subjects were identified. Duodenal samples from SIBO subjects had 4x103-fold higher counts than non-SIBO subjects when plated on MacConkey agar (P<0.0001), and 3.8-fold higher counts when plated on blood agar (P<0.0001). Twenty subjects had also undergone lactulose hydrogen breath tests (LHBTs), of whom 7/20 had SIBO. At the 90-minute timepoint, 4/7 SIBO subjects had positive LHBTs (rise in hydrogen (H2) ≥ 20 ppm above baseline), as compared to 2/13 non-SIBO subjects. 16S ribosomal RNA (rRNA) sequencing revealed that SIBO subjects had 4.31-fold higher relative abundance of Proteobacteria (FDR P<0.0001) and 1.64-fold lower Firmicutes (P<0.0003) than non-SIBO subjects. This increased relative abundance of Proteobacteria correlated with decreased α-diversity in SIBO subjects (Spearman R = 0.4866, P<0.0001) Specific increases in class Gammaproteobacteria correlated with the area-under-the-curve for H2 for 0-90 mins during LHBT (R = 0.630, P = 0.002). Increases in Gammaproteobacteria resulted primarily from higher relative abundances of the family Enterobacteriaceae (FDR P<0.0001), which correlated with the symptom of bloating (Spearman R = 0.185, 2-tailed P = 0.028). Increases in family Aeromonadaceae correlated with urgency with bowel movement (Spearman R = 0.186, 2-tailed P = 0.028). These results validate the >103 CFU/mL cutoff for the definition of SIBO, and also reveal specific overgrowth of Proteobacteria in SIBO vs. non-SIBO subjects, coupled with an altered Proteobacterial profile that correlates with symptom severity. Future research may elucidate host-microbiome interactions underlying these symptoms in SIBO patients.
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Olad A, Eslamzadeh M, Katiraee F, Mirmohseni A. Evaluation of in vitro anti-fungal properties of allicin loaded ion cross-linked poly (AA-co-AAm)/PVA/Cloisite 15A Nanocomposite hydrogel films as wound dressing materials. JOURNAL OF POLYMER RESEARCH 2020. [DOI: 10.1007/s10965-020-02072-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Fidel PL, Yano J, Esher SK, Noverr MC. Applying the Host-Microbe Damage Response Framework to Candida Pathogenesis: Current and Prospective Strategies to Reduce Damage. J Fungi (Basel) 2020; 6:jof6010035. [PMID: 32168864 PMCID: PMC7151217 DOI: 10.3390/jof6010035] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 03/05/2020] [Accepted: 03/06/2020] [Indexed: 12/16/2022] Open
Abstract
Disease is a complex outcome that can occur as a result of pathogen-mediated damage, host-mediated damage or both. This has led to the revolutionary concept of the damage response framework (DRF) that defines microbial virulence as a function of host immunity. The DRF outlines six scenarios (classes) of host damage or beneficial outcomes, depending on the microbe and the strength of the immune response. Candida albicans is uniquely adapted to its human host and can exist as either a commensal, colonizing various anatomical sites without causing notable damage, or as a pathogen, with the ability to cause a diverse array of diseases, ranging from mucosal to invasive systemic infections that result in varying levels of microbe-mediated and/or host-mediated damage. We recently categorized six different forms of candidiasis (oropharyngeal, hematogenous, intra-abdominal, gastrointestinal, denture stomatitis, and vulvovaginitis) into independent DRF classes, supporting a contemporary view of unique mechanisms of pathogenesis for these Candida infections. In this review, we summarize the evidence for the pathogenesis of these various forms of candidiasis in the context of the DRF with the further intent to provide insights into strategies to achieve a level of host response or outcome otherwise, that limits host damage.
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Affiliation(s)
- Paul L. Fidel
- Center of Excellence in Oral and Craniofacial Biology, Louisiana State University Health Sciences Center School of Dentistry, New Orleans, LA 70119, USA;
- Correspondence: ; Tel.: +1-504-941-8425
| | - Junko Yano
- Center of Excellence in Oral and Craniofacial Biology, Louisiana State University Health Sciences Center School of Dentistry, New Orleans, LA 70119, USA;
| | - Shannon K. Esher
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA; (S.K.E.); (M.C.N.)
| | - Mairi C. Noverr
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA; (S.K.E.); (M.C.N.)
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Abstract
Small intestinal bacterial overgrowth is defined as the presence of excessive numbers of bacteria in the small bowel, causing gastrointestinal symptoms. This guideline statement evaluates criteria for diagnosis, defines the optimal methods for diagnostic testing, and summarizes treatment options for small intestinal bacterial overgrowth. This guideline provides an evidence-based evaluation of the literature through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the available evidence was not appropriate for a formal GRADE recommendation, key concepts were developed using expert consensus.
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Wang J, Liu Y, Zhao G, Gao J, Liu J, Wu X, Xu C, Li Y. Integrated proteomic and metabolomic analysis to study the effects of spaceflight on Candida albicans. BMC Genomics 2020; 21:57. [PMID: 31952470 PMCID: PMC6969454 DOI: 10.1186/s12864-020-6476-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 01/09/2020] [Indexed: 11/23/2022] Open
Abstract
Background Candida albicans is an opportunistic pathogenic yeast, which could become pathogenic in various stressful environmental factors including the spaceflight environment. In this study, we aim to explore the phenotypic changes and possible mechanisms of C. albicans after exposure to spaceflight conditions. Results The effect of C. albicans after carried on the “SJ-10” satellite for 12 days was evaluated by proliferation, morphology, environmental resistance and virulence experiment. The result showed that the proliferation rate, biofilm formation, antioxidant capacity, cytotoxicity and filamentous morphology of C. albicans were increased in the spaceflight group compared to the control group. Proteomics and metabolomics technologies were used to analyze the profiles of proteins and metabolites in C. albicans under spaceflight conditions. Proteomic analysis identified 548 up-regulated proteins involved in the ribosome, DNA replication, base excision repair and sulfur metabolism in the spaceflight group. Moreover, 332 down-regulated proteins related to metabolic processes were observed. The metabolomic analysis found five differentially expressed metabolites. The combined analysis of proteomic and metabolomic revealed the accumulation of cysteine and methionine in C. albicans after spaceflight. Conclusions Mechanisms that could explain the results in the phenotypic experiment of C. albicans were found through proteomic and metabolomic analysis. And our data provide an important basis for the assessment of the risk that C. albicans could cause under spaceflight environment.
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Affiliation(s)
- Jiaping Wang
- China Astronaut Research and Training Center, Beijing, 100094, China
| | - Yu Liu
- China Astronaut Research and Training Center, Beijing, 100094, China
| | - Guangxian Zhao
- China Astronaut Research and Training Center, Beijing, 100094, China
| | - Jianyi Gao
- China Astronaut Research and Training Center, Beijing, 100094, China
| | - Junlian Liu
- China Astronaut Research and Training Center, Beijing, 100094, China
| | - Xiaorui Wu
- China Astronaut Research and Training Center, Beijing, 100094, China
| | - Chong Xu
- China Astronaut Research and Training Center, Beijing, 100094, China
| | - Yongzhi Li
- China Astronaut Research and Training Center, Beijing, 100094, China.
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Wang T, Dong J, Yin H, Zhang G. Blue light therapy to treat candida vaginitis with comparisons of three wavelengths: an in vitro study. Lasers Med Sci 2020; 35:1329-1339. [PMID: 31900692 DOI: 10.1007/s10103-019-02928-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 11/27/2019] [Indexed: 01/31/2023]
Abstract
Anti-fungal blue light (ABL) therapies have been widely studied to treat various microbial infections in the literature. The blue light with wavelengths ranging from 400 to 470 nm has been reported to be effective to inhibit various kinds of bacteria and fungi. The existing studies usually report the viability rates of the pathogens under the irradiation of the blue light with different dosage parameters. However, to the best of our knowledge, there is still no work especially focusing on studying the effect of ABL therapies on treating candida vaginitis, where it is important to study the viability of both the Candida albicans (C. albicans) and the human vaginal epithelial cells. It is the purpose of this work to conduct ABL experiments on both of these two cells, analyze the effects, and determine the best ABL wavelength out of three candidates, i.e., 405-nm, 415-nm, and 450-nm wavelength. The viability rates of the C. albicans and the human vaginal epithelial cells irradiated by the three blue LED light sources were measured, whose irradiance (power density) were all set to 50 mW/cm2. The dynamic viability models of the C. albicans and the epithelial cells were built based on the experimental data. Moreover, in this work, we also built a functional relationship between the viability of these two types of cells, by which we further compared the effects of the blue light irradiation on both the C. albicans and vaginal epithelial cells. The experimental data showed that when an approximately 80% inhibiting rate of the C. albicans was achieved, the survival rates of the epithelial cells were 0.6700, 0.7748, and 0.6027, respectively for the treatment by the 405-nm, 415-nm, and 450-nm wavelength light. On the other hand, by simulating the functional relationship between the viability of the two types of cells, the survival rates of the epithelial cells became 0.5783, 0.6898, and 0.1918 respectively using the 405-nm, 415-nm and 450-nm wavelength light, when the C. albicans was completely inhibited. Therefore, both the experimental data and the model simulation results have demonstrated that the 415-nm light has a more effective anti-fungal result with less damage to the epithelial cells than the 405-nm and 450-nm light.
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Affiliation(s)
- Tianfeng Wang
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China
| | - Jianfei Dong
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.
| | - Huancai Yin
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China
| | - Guoqi Zhang
- Department of Microelectronics, Delft University of Technology, Delft, The Netherlands
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44
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Barros LL, Farias AQ, Rezaie A. Gastrointestinal motility and absorptive disorders in patients with inflammatory bowel diseases: Prevalence, diagnosis and treatment. World J Gastroenterol 2019; 25:4414-4426. [PMID: 31496621 PMCID: PMC6710178 DOI: 10.3748/wjg.v25.i31.4414] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 07/04/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD), Crohn`s disease and ulcerative colitis, are chronic conditions associated with high morbidity and healthcare costs. The natural history of IBD is variable and marked by alternating periods of flare and remission. Even though the use of newer therapeutic targets has been associated with higher rates of mucosal healing, a great proportion of IBD patients remain symptomatic despite effective control of inflammation. These symptoms may include but not limited to abdominal pain, dyspepsia, diarrhea, urgency, fecal incontinence, constipation or bloating. In this setting, commonly there is an overlap with gastrointestinal (GI) motility and absorptive disorders. Early recognition of these conditions greatly improves patient care and may decrease the risk of mistreatment. Therefore, in this review we describe the prevalence, diagnosis and treatment of GI motility and absorptive disorders that commonly affect patients with IBD.
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Affiliation(s)
- Luísa Leite Barros
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo 05403-000, Brazil
| | - Alberto Queiroz Farias
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo 05403-000, Brazil
| | - Ali Rezaie
- Division of Gastroenterology, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
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45
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The Use of Copper as an Antimicrobial Agent in Health Care, Including Obstetrics and Gynecology. Clin Microbiol Rev 2019; 32:32/4/e00125-18. [PMID: 31413046 DOI: 10.1128/cmr.00125-18] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Health care-associated infections (HAIs) are a global problem associated with significant morbidity and mortality. Controlling the spread of antimicrobial-resistant bacteria is a major public health challenge, and antimicrobial resistance has become one of the most important global problems in current times. The antimicrobial effect of copper has been known for centuries, and ongoing research is being conducted on the use of copper-coated hard and soft surfaces for reduction of microbial contamination and, subsequently, reduction of HAIs. This review provides an overview of the historical and current evidence of the antimicrobial and wound-healing properties of copper and explores its possible utility in obstetrics and gynecology.
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46
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O'Brien DM, Vallieres C, Alexander C, Howdle SM, Stockman RA, Avery SV. Epoxy-amine oligomers from terpenes with applications in synergistic antifungal treatments. J Mater Chem B 2019; 7:5222-5229. [PMID: 31369021 DOI: 10.1039/c9tb00878k] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
A bis-epoxide monomer was synthesised in two steps from (R)-carvone, a terpenoid renewable feedstock derived from spearmint oil, and used to prepare β-aminoalcohol oligomers in polyaddition reactions with bis-amines without requiring solvent or catalyst. A sub-set of the resultant materials were readily water soluble and were investigated for antifungal activity in combination with the fungicide iodopropynyl-butylcarbamate (IPBC) or the antifungal drug amphotericin B. The oligo-(β-aminoalcohol)s alone were inactive against Trichoderma virens and Candida albicans but in combination with IPBC and amphotericin B demonstrated synergistic growth-inhibition of both fungi. Quantitative analysis showed that the presence of the terpene-based oligomers decreased the minimum inhibitory concentration (MIC) of IPBC by up to 64-fold and of amphotericin B by 8-fold. The efficacy of the combined formulation was further demonstrated with agar disk diffusion assays, which revealed that IPBC and amphotericin B reduced the growth of the fungi, as shown by zones of inhibition, to a greater extent when in the presence of the oligo-(β-aminoalcohol)s. These data suggest potential future use of these renewable feedstock derived oligomers in antifungal material and related biomedical applications.
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Affiliation(s)
- Dara M O'Brien
- School of Chemistry, University Park University of Nottingham, NG7 2RD, UK.
| | - Cindy Vallieres
- School of Life Sciences, University Park University of Nottingham, NG7 2RD, UK
| | - Cameron Alexander
- School of Pharmacy, University Park University of Nottingham, NG7 2RD, UK
| | - Steven M Howdle
- School of Chemistry, University Park University of Nottingham, NG7 2RD, UK.
| | - Robert A Stockman
- School of Chemistry, University Park University of Nottingham, NG7 2RD, UK.
| | - Simon V Avery
- School of Life Sciences, University Park University of Nottingham, NG7 2RD, UK
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47
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Correlation between Jejunal Microbial Diversity and Muscle Fatty Acids Deposition in Broilers Reared at Different Ambient Temperatures. Sci Rep 2019; 9:11022. [PMID: 31363155 PMCID: PMC6667446 DOI: 10.1038/s41598-019-47323-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 07/12/2019] [Indexed: 12/14/2022] Open
Abstract
Temperature, which is an important environmental factor in broiler farming, can significantly influence the deposition of fatty acids in muscle. 300 one-day-old broiler chicks were randomly divided into three groups and reared at high, medium and low temperatures (HJ, MJ and LJ), respectively. Breast muscle and jejunal chyme samples were collected and subjected to analyses of fatty acid composition and 16S rRNA gene sequencing. Through spearman’s rank correlation coefficient, the data were used to characterize the correlation between jejunal microbial diversity and muscle fatty acid deposition in the broilers. The results showed that Achromobacter, Stenotrophomonas, Pandoraea, Brevundimonas, Petrobacter and Variovorax were significantly enriched in the MJ group, and all of them were positively correlated with the fatty acid profiling of muscle and multiple lipid metabolism signaling pathways. Lactobacillus was significantly enriched in the HJ group and exhibited a positive correlation with fatty acid deposition. Pyramidobacter, Dialister, Bacteroides and Selenomonas were significantly enriched in the LJ group and displayed negative correlation with fatty acid deposition. Taken together, this study demonstrated that the jejunal microflora manifested considerable changes at high and low ambient temperatures and that jejunal microbiota changes were correlated with fatty acid deposition of muscle in broilers.
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48
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Mueller KD, Zhang H, Serrano CR, Billmyre RB, Huh EY, Wiemann P, Keller NP, Wang Y, Heitman J, Lee SC. Gastrointestinal microbiota alteration induced by Mucor circinelloides in a murine model. J Microbiol 2019; 57:509-520. [PMID: 31012059 PMCID: PMC6737537 DOI: 10.1007/s12275-019-8682-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 01/10/2019] [Accepted: 01/15/2019] [Indexed: 12/12/2022]
Abstract
Mucor circinelloides is a pathogenic fungus and etiologic agent of mucormycosis. In 2013, cases of gastrointestinal illness after yogurt consumption were reported to the US FDA, and the producer found that its products were contaminated with Mucor. A previous study found that the Mucor strain isolated from an open contaminated yogurt exhibited virulence in a murine systemic infection model and showed that this strain is capable of surviving passage through the gastrointestinal tract of mice. In this study, we isolated another Mucor strain from an unopened yogurt that is closely related but distinct from the first Mucor strain and subsequently examined if Mucor alters the gut microbiota in a murine host model. DNA extracted from a ten-day course of stool samples was used to analyze the microbiota in the gastrointestinal tracts of mice exposed via ingestion of Mucor spores. The bacterial 16S rRNA gene and fungal ITS1 sequences obtained were used to identify taxa of each kingdom. Linear regressions revealed that there are changes in bacterial and fungal abundance in the gastrointestinal tracts of mice which ingested Mucor. Furthermore, we found an increased abundance of the bacterial genus Bacteroides and a decreased abundance of the bacteria Akkermansia muciniphila in the gastrointestinal tracts of exposed mice. Measurements of abundances show shifts in relative levels of multiple bacterial and fungal taxa between mouse groups. These findings suggest that exposure of the gastrointestinal tract to Mucor can alter the microbiota and, more importantly, illustrate an interaction between the intestinal mycobiota and bacteriota. In addition, Mucor was able to induce increased permeability in epithelial cell monolayers in vitro, which might be indicative of unstable intestinal barriers. Understanding how the gut microbiota is shaped is important to understand the basis of potential methods of treatment for gastrointestinal illness. How the gut microbiota changes in response to exposure, even by pathogens not considered to be causative agents of food-borne illness, may be important to how commercial food producers prevent and respond to contamination of products aimed at the public. This study provides evidence that the fungal microbiota, though understudied, may play an important role in diseases of the human gut.
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Affiliation(s)
- Katherine D Mueller
- South Texas Center for Emerging Infectious Diseases (STCEID), Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA
| | - Hao Zhang
- South Texas Center for Emerging Infectious Diseases (STCEID), Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA
| | - Christian R Serrano
- South Texas Center for Emerging Infectious Diseases (STCEID), Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA
| | - R Blake Billmyre
- Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA
| | - Eun Young Huh
- South Texas Center for Emerging Infectious Diseases (STCEID), Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA
| | - Philipp Wiemann
- Department of Medical Microbiology and Immunology, University of Wisconsin at Madison, Madison, WI, USA
| | - Nancy P Keller
- Department of Medical Microbiology and Immunology, University of Wisconsin at Madison, Madison, WI, USA
| | - Yufeng Wang
- South Texas Center for Emerging Infectious Diseases (STCEID), Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA
| | - Joseph Heitman
- Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA
| | - Soo Chan Lee
- South Texas Center for Emerging Infectious Diseases (STCEID), Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA.
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49
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Anderson SD, Gwenin VV, Gwenin CD. Magnetic Functionalized Nanoparticles for Biomedical, Drug Delivery and Imaging Applications. NANOSCALE RESEARCH LETTERS 2019; 14:188. [PMID: 31147786 PMCID: PMC6542970 DOI: 10.1186/s11671-019-3019-6] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 05/17/2019] [Indexed: 05/12/2023]
Abstract
Medicine is constantly looking for new and improved treatments for diseases, which need to have a high efficacy and be cost-effective, creating a large demand on scientific research to discover such new treatments. One important aspect of any treatment is the ability to be able to target only the illness and not cause harm to another healthy part of the body. For this reason, metallic nanoparticles have been and are currently being extensively researched for their possible medical uses, including medical imaging, antibacterial and antiviral applications. Superparamagnetic metal nanoparticles possess properties that allow them to be directed around the body with a magnetic field or directed to a magnetic implant, which opens up the potential to conjugate various bio-cargos to the nanoparticles that could then be directed for treatment in the body. Here we report on some of the current bio-medical applications of various metal nanoparticles, including single metal nanoparticles, functionalized metal nanoparticles, and core-shell metal nanoparticles using a core of Fe3O4 as well as synthesis methods of these core-shell nanoparticles.
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Affiliation(s)
- Simon D Anderson
- School of Natural Sciences, College of Environmental Sciences and Engineering, Bangor University, Bangor, LL57 2UW, UK
| | - Vanessa V Gwenin
- School of Natural Sciences, College of Environmental Sciences and Engineering, Bangor University, Bangor, LL57 2UW, UK
| | - Christopher D Gwenin
- School of Natural Sciences, College of Environmental Sciences and Engineering, Bangor University, Bangor, LL57 2UW, UK.
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50
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Candida albicans-induced acute lung injury through activating several inflammatory signaling pathways in mice. Int Immunopharmacol 2019; 72:275-283. [PMID: 31005037 DOI: 10.1016/j.intimp.2019.04.026] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 03/20/2019] [Accepted: 04/12/2019] [Indexed: 02/06/2023]
Abstract
Candida albicans infection-induced acute lung injury is one of the most prevalent diseases in immunosuppressive individual. Nevertheless, the mechanism by which Candida albicans induced acute lung injury remains unclear. The present study investigated the mechanism by which Candida albicans induced acute lung injury in mice. Mice were randomly divided into four groups and intratracheally injected with 60 μl Candida albicans (106 CFU) or normal saline. Half of the mice were sacrificed at 6 h after Candida albicans. The rest of the mice for survival test were observed until 7 d after Candida albicans. As expected, immunosuppression aggravated Candida albicans-induced acute lung injury and death in mice. Additionally, Candida albicans infection elevated mRNA levels of pro-inflammatory and chemokines in lungs and the levels of IL-6, IL-1β and IL-17 in serum. Further study showed that Candida albicans promoted nuclear translocation of NF-κB p50 and p65 subunits in pulmonary epithelial cells and interstitial cells. Candida albicans induced pulmonary p38, ERK1/2 and Akt phosphorylation in normal and immunosuppressive mice. Moreover, Candida albicans infection activated pulmonary STAT3 signaling in normal and immunosuppressive mice. Overall, these results suggest that Candida albicans induced acute lung injury and death may be through activating several inflammatory signaling pathways.
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