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Understanding the impact of antibiotic perturbation on the human microbiome.
Schwartz, DJ, Langdon, AE, Dantas, G
Genome medicine. 2020;(1):82
Abstract
The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome's ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.
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Breast Pathology That Contributes to Dysfunction of Human Lactation: a Spotlight on Nipple Blebs.
Mitchell, KB, Johnson, HM
Journal of mammary gland biology and neoplasia. 2020;(2):79-83
Abstract
Nipple blebs are blister-like fibrinous lesions that form on the surface of the nipple during lactation, and can result in orifice obstruction and mastitis. They likely result from superficial extension of underlying ductal plugging, and can present concurrently with hyperlactation and mammary dysbiosis. Despite their prevalence, few formal reports on nipple blebs exist. In this perspective, we review the experience of a breastfeeding medicine practice that receives referrals for patients with nipple blebs, and provide preliminary insight into etiology, management, and outcomes of these lesions.
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Scavenging Bacterial Siderophores with Engineered Lipocalin Proteins as an Alternative Antimicrobial Strategy.
Dauner, M, Skerra, A
Chembiochem : a European journal of chemical biology. 2020;(5):601-606
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Abstract
Iron acquisition mediated by siderophores, high-affinity chelators for which bacteria have evolved specific synthesis and uptake mechanisms, plays a crucial role in microbiology and in host-pathogen interactions. In the ongoing fight against bacterial infections, this area has attracted biomedical interest. Beyond several approaches to interfere with siderophore-mediated iron uptake from medicinal and immunochemistry, the development of high-affinity protein scavengers that tightly complex the siderophores produced by pathogenic bacteria has appeared as a novel strategy. Such binding proteins have been engineered based on siderocalin-also known as lipocalin 2-an endogenous human scavenger of enterobactin and bacillibactin that controls the systemic spreading of commensal bacteria such as Escherichia coli. By using combinatorial protein design, siderocalin was reshaped to bind several siderophores from Pseudomonas aeruginosa and, in particular, petrobactin from Bacillus anthracis, none of which is recognized by the natural protein. Such engineered versions of siderocalin effectively suppress the growth of corresponding pathogenic bacteria by depriving them of their iron supply and offer the potential to complement antibiotic therapy in situations of acute or persistent infection.
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An Overview of Ozone Therapy for Treating Foot Ulcers in Patients With Diabetes.
Wen, Q, Chen, Q
The American journal of the medical sciences. 2020;(2):112-119
Abstract
Diabetic foot ulcer (DFU) is one of the most common and severe complications of diabetes mellitus, which is becoming increasingly prevalent throughout the world, with high mortality and morbidity. Because of the complex pathophysiological processes involved, DFU is difficult to treat effectively with traditional therapies. Ozone therapy, an emerging method, has been reported as potentially beneficial for closure of DFUs and may gradually move to the forefront of clinical practice. Possible mechanisms of action include antioxidant capacity, pathogen inactivation, vascular and endogenous growth factor modulation, and immune system activation. However, some researchers are skeptical about its safety, and clinical trials are lacking. This article reviews the current research and application of ozone therapy for DFUs.
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Acute pancreatitis.
Boxhoorn, L, Voermans, RP, Bouwense, SA, Bruno, MJ, Verdonk, RC, Boermeester, MA, van Santvoort, HC, Besselink, MG
Lancet (London, England). 2020;(10252):726-734
Abstract
Acute pancreatitis is an unpredictable and potentially lethal disease. The prognosis mainly depends on the development of organ failure and secondary infection of pancreatic or peripancreatic necrosis. In the past 10 years, treatment of acute pancreatitis has moved towards a multidisciplinary, tailored, and minimally invasive approach. Despite improvements in treatment and critical care, severe acute pancreatitis is still associated with high mortality rates. In this Seminar, we outline the latest evidence on diagnostic and therapeutic strategies for acute pancreatitis.
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MCOLN1/TRPML1 inhibition - a novel strategy used by Helicobacter pylori to escape autophagic killing and antibiotic eradication therapy in vivo.
Capurro, MI, Prashar, A, Jones, NL
Autophagy. 2020;(1):169-170
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Abstract
Inhibition of host macroautophagy/autophagy is one of the strategies used by several intracellular pathogens, including H. pylori, to escape killing. Here we discuss our recent work that revealed the novel mechanism by which the vacuolating cytotoxin A (VacA) produced by H. pylori inhibits lysosomal and autophagic killing. We discovered that VacA impairs the activity of the lysosomal calcium channel MCOLN1/TRPML1 leading to the formation of enlarged, dysfunctional lysosomes and autophagosomes that serve as an intracellular niche, which allows the bacteria to escape eradication therapy.
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Iron Metabolism at the Interface between Host and Pathogen: From Nutritional Immunity to Antibacterial Development.
Marchetti, M, De Bei, O, Bettati, S, Campanini, B, Kovachka, S, Gianquinto, E, Spyrakis, F, Ronda, L
International journal of molecular sciences. 2020;(6)
Abstract
Nutritional immunity is a form of innate immunity widespread in both vertebrates and invertebrates. The term refers to a rich repertoire of mechanisms set up by the host to inhibit bacterial proliferation by sequestering trace minerals (mainly iron, but also zinc and manganese). This strategy, selected by evolution, represents an effective front-line defense against pathogens and has thus inspired the exploitation of iron restriction in the development of innovative antimicrobials or enhancers of antimicrobial therapy. This review focuses on the mechanisms of nutritional immunity, the strategies adopted by opportunistic human pathogen Staphylococcus aureus to circumvent it, and the impact of deletion mutants on the fitness, infectivity, and persistence inside the host. This information finally converges in an overview of the current development of inhibitors targeting the different stages of iron uptake, an as-yet unexploited target in the field of antistaphylococcal drug discovery.
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Antimicrobial Capacity of Plant Polyphenols against Gram-positive Bacteria: A Comprehensive Review.
Álvarez-Martínez, FJ, Barrajón-Catalán, E, Encinar, JA, Rodríguez-Díaz, JC, Micol, V
Current medicinal chemistry. 2020;(15):2576-2606
Abstract
BACKGROUND Multi-drug-resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA) disseminate rapidly amongst patients in healthcare facilities and suppose an increasingly important cause of community-associated infections and associated mortality. The development of effective therapeutic options against resistant bacteria is a public health priority. Plant polyphenols are structurally diverse compounds that have been used for centuries for medicinal purposes, including infections treatment and possess, not only antimicrobial activity, but also antioxidant, anti-inflammatory and anticancer activities among others. Based on the existing evidence on the polyphenols' antibacterial capacity, polyphenols may be postulated as an alternative or complementary therapy for infectious diseases. OBJECTIVE To review the antimicrobial activity of plant polyphenols against Gram-positive bacteria, especially against S. aureus and its resistant strains. Determine the main bacterial molecular targets of polyphenols and their potential mechanism of action. METHODOLOGY The most relevant reports on plant polyphenols' antibacterial activity and their putative molecular targets were studied. We also performed virtual screening of thousand different polyphenols against proteins involved in the peptidoglycan biosynthesis to find potential valuable bioactive compounds. The bibliographic information used in this review was obtained from MEDLINE via PubMed. RESULTS Several polyphenols: phenolic acids, flavonoids (especially flavonols), tannins, lignans, stilbenes and combinations of these in botanical mixtures, have exhibited significant antibacterial activity against resistant and non-resistant Gram-positive bacteria at low μg/mL range MIC values. Their mechanism of action is quite diverse, targeting cell wall, lipid membrane, membrane receptors and ion channels, bacteria metabolites and biofilm formation. Synergic effects were also demonstrated for some combinations of polyphenols and antibiotics. CONCLUSION Plant polyphenols mean a promising source of antibacterial agents, either alone or in combination with existing antibiotics, for the development of new antibiotic therapies.
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Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation.
Schwabkey, ZI, Jenq, RR
Annual review of medicine. 2020;:137-148
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Abstract
The microbiome is an integrated part of the human body that can modulate a variety of disease processes and affect prognosis, treatment response, complications, and outcomes. The importance of allogeneic hematopoietic cell transplantation in cancer treatment has resulted in extensive investigations on the interaction between the microbiome and this treatment modality. These investigations are beginning to lead to clinical trials of microbiome-targeted interventions. Here we review some of these discoveries and describe strategies being investigated to manipulate the microbiome for favorable outcomes, such as the proper selection and timing of antibiotics, type of diet and route of administration, probiotics, prebiotics, and fecal microbiota transplantation.
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Gut microbiota and obesity: Impact of antibiotics and prebiotics and potential for musculoskeletal health.
Klancic, T, Reimer, RA
Journal of sport and health science. 2020;(2):110-118
Abstract
Obesity is a complex disease with multiple contributing factors. One of the most intensely studied factors during the past decade has been the gut microbiota, which is the community of all microbes in the intestinal tract. The gut microbiota, via energy extraction, inflammation, and other actions, is now recognized as an important player in the pathogenesis of obesity. Dysbiosis, or an imbalance in the microbial community, can initiate a cascade of metabolic disturbances in the host. Early life is a particularly important period for the development of the gut microbiota, and perturbations such as with antibiotic exposure can have long-lasting consequences for host health. In early life and throughout the life span, diet is one of the most important factors that shape the gut microbiota. Although diets high in fat and sugar have been shown to contribute to dysbiosis and disease, dietary fiber is recognized as an important fermentative fuel for the gut microbiota and results in the production of short-chain fatty acids that can act as signaling molecules in the host. One particular type of fiber, prebiotic fiber, contributes to changes in the gut microbiota, the most notable of which is an increase in the abundance of Bifidobacterium. This review highlights our current understanding of the role of gut microbiota in obesity development and the ways in which manipulating the microbiota through dietary means, specifically prebiotics, could contribute to improved health in the host, including musculoskeletal health.