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1.
The importance of airway and lung microbiome in the critically ill.
Martin-Loeches, I, Dickson, R, Torres, A, Hanberger, H, Lipman, J, Antonelli, M, de Pascale, G, Bozza, F, Vincent, JL, Murthy, S, et al
Critical care (London, England). 2020;(1):537
Abstract
During critical illness, there are a multitude of forces such as antibiotic use, mechanical ventilation, diet changes and inflammatory responses that could bring the microbiome out of balance. This so-called dysbiosis of the microbiome seems to be involved in immunological responses and may influence outcomes even in individuals who are not as vulnerable as a critically ill ICU population. It is therefore probable that dysbiosis of the microbiome is a consequence of critical illness and may, subsequently, shape an inadequate response to these circumstances.Bronchoscopic studies have revealed that the carina represents the densest site of bacterial DNA along healthy airways, with a tapering density with further bifurcations. This likely reflects the influence of micro-aspiration as the primary route of microbial immigration in healthy adults. Though bacterial DNA density grows extremely sparse at smaller airways, bacterial signal is still consistently detectable in bronchoalveolar lavage fluid, likely reflecting the fact that lavage via a wedged bronchoscope samples an enormous surface area of small airways and alveoli. The dogma of lung sterility also violated numerous observations that long predated culture-independent microbiology.The body's resident microbial consortia (gut and/or respiratory microbiota) affect normal host inflammatory and immune response mechanisms. Disruptions in these host-pathogen interactions have been associated with infection and altered innate immunity.In this narrative review, we will focus on the rationale and current evidence for a pathogenic role of the lung microbiome in the exacerbation of complications of critical illness, such as acute respiratory distress syndrome and ventilator-associated pneumonia.
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2.
Review on the Alteration of Gut Microbiota: The Role of HIV Infection and Old Age.
Ashuro, AA, Lobie, TA, Ye, DQ, Leng, RX, Li, BZ, Pan, HF, Fan, YG
AIDS research and human retroviruses. 2020;(7):556-565
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Abstract
Human immunodeficiency virus (HIV) infection results in gut microbiota alteration and this is associated with immune activation and chronic inflammation. The gastrointestinal tract is a primary site of viral replication and thus HIV-induced loss of T-helper (Th) cells in the gut causes impairments in intestinal barriers, resulting in disruptions in intestinal immunity and precipitating into gut dysbiosis. Here, we show that late HIV diagnosis can negatively affect the immunological, virological, and clinical prognosis of the patients with its higher implication at an older age. Further, the review indicates that antiretroviral therapy affects the gut microbiota. We discussed the use of probiotics and prebiotics that have been indicated to play a promising role in reversing gut microbiota alteration in HIV patients. Though there are several studies reported with regard to such alterations in gut microbiota regarding HIV infection, there is a need to provide comprehensive updates. It is, therefore, the objective of this review to present most recently available evidence on the alteration of gut microbiota among HIV patients.
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3.
The trace aminergic system: a gender-sensitive therapeutic target for IBS?
Pretorius, L, Smith, C
Journal of biomedical science. 2020;(1):95
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Abstract
Due to a lack of specific or sensitive biomarkers, drug discovery advances have been limited for individuals suffering from irritable bowel syndrome (IBS). While current therapies provide symptomatic relief, inflammation itself is relatively neglected, despite the presence of chronic immune activation and innate immune system dysfunction. Moreover, considering the microgenderome concept, gender is a significant aetiological risk factor. We believe that we have pinpointed a "missing link" that connects gender, dysbiosis, diet, and inflammation in the context of IBS, which may be manipulated as therapeutic target. The trace aminergic system is conveniently positioned at the interface of the gut microbiome, dietary nutrients and by-products, and mucosal immunity. Almost all leukocyte populations express trace amine associated receptors and significant amounts of trace amines originate from both food and the gut microbiota. Additionally, although IBS-specific data are sparse, existing data supports an interpretation in favour of a gender dependence in trace aminergic signalling. As such, trace aminergic signalling may be altered by fluctuations of especially female reproductive hormones. Utilizing a multidisciplinary approach, this review discusses potential mechanisms of actions, which include hyperreactivity of the immune system and aberrant serotonin signalling, and links outcomes to the symptomology clinically prevalent in IBS. Taken together, it is feasible that the additional level of regulation by the trace aminergic system in IBS has been overlooked, until now. As such, we suggest that components of the trace aminergic system be considered targets for future therapeutic action, with the specific focus of reducing oxidative stress and inflammation.
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Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function.
Sharpton, SR, Ajmera, V, Loomba, R
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(2):296-306
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Abstract
The gut microbiome, a diverse microbial community in the gastrointestinal tract, plays a pivotal role in the maintenance of health. The gut microbiome metabolizes dietary and host-derived molecules to produce bioactive metabolites, which have a wide array of effects on host metabolism and immunity. 'Dysbiosis' of the gut microbiome, commonly considered as perturbation of microbiome diversity and composition, has been associated with intestinal and extra-intestinal diseases, including nonalcoholic fatty liver disease (NAFLD). A number of endogenous and exogenous factors, such as nutritional intake and xenobiotic exposure, can alter the gut microbiome. We will review the evolving methods for studying the gut microbiome and how these profiling techniques have been utilized to further our understanding of the gut microbial community composition and functional potential in the clinical spectrum of NAFLD. We will highlight microbiome-host interactions that may contribute to the pathogenesis of NAFLD, with a primary focus on mechanisms related to the metabolic output of the gut microbiome. Finally, we will discuss potential therapeutic implications of the gut microbiome in NAFLD.
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Probiotic research in neonates with congenital gastrointestinal surgical conditions - Now is the time.
Rao, SC, Patole, SK
Microbial biotechnology. 2019;(2):254-258
Abstract
Neonates with congenital gastrointestinal surgical conditions (CGISC) receive parenteral nutrition, get exposed to multiple courses of antibiotics, undergo invasive procedures, and are nursed in intensive care units. They do not receive early enteral feeding and have limited opportunities for skin to skin contact with their mothers. Many of these infants receive gastric acid suppression therapies. All these factors increase the risk of gut dysbiosis in these infants. Gut dysbiosis is known to be associated with increased risk of infections and other morbidities in ICU patients. Experimental studies have shown that probiotics inhibit gut colonization with pathogenic bacteria, enhance gut barrier function, facilitate colonization with healthy commensals, protect from enteropathogenic infection through production of acetate, reduce antimicrobial resistance, enhance innate immunity, and increase the maturation of the enteric nervous system and promote gut peristalsis. Through these mechanisms, probiotics have the potential to decrease the risk of sepsis and inflammation, improve feed tolerance and minimise cholestasis in neonates with CGISC. Among preterm non-surgical infants, evidence from more than 35 RCTs and multiple observational studies have shown probiotics to be safe and beneficial. A RCT in neonates (N=24) with gastroschisis found that probiotic supplementation partially attenuated gut dysbiosis. Two ongoing RCTs (total N=168) in neonates with gastrointestinal surgical conditions are expected to provide feasibility data to enable the conduct of large RCTs. Rigorous quality assurance of the probiotic product, ongoing microbial surveillance and clinical vigilance are warranted while conducting such RCTs.
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Prebiotics and Probiotics in Digestive Health.
Quigley, EMM
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(2):333-344
Abstract
As the importance of the gut microbiota in health and disease is increasingly recognized interest in interventions that can modulate the microbiota and its interactions with its host has soared. Apart from diet, prebiotics and probiotics represent the most commonly used substances taken in an effort to sustain a healthy microbiome or restore balance when it is believed bacterial homeostasis has been disturbed in disease. While a considerable volume of basic science attests to the ability of various prebiotic molecules and probiotic strains to beneficially influence host immune responses, metabolic processes and neuro-endocrine pathways, the evidence base from human studies leaves much to be desired. This translational gap owes much to the manner in which this sector is regulated but also speaks to the challenges that confront the investigator who seeks to explore microbiota modulation in either healthy populations or those who suffer from common digestive ailments. For many products marketed as probiotics, some of the most fundamental issues relating to quality control, such as characterization, formulation, viability safety are scarcely addressed.
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The Gut Microbiome in Inflammatory Bowel Disease: Lessons Learned From Other Immune-Mediated Inflammatory Diseases.
Knox, NC, Forbes, JD, Peterson, CL, Van Domselaar, G, Bernstein, CN
The American journal of gastroenterology. 2019;(7):1051-1070
Abstract
There is a growing appreciation for the role of the gut microbiome in human health and disease. Aided by advances in sequencing technologies and analytical methods, recent research has shown the healthy gut microbiome to possess considerable diversity and functional capacity. Dysbiosis of the gut microbiota is believed to be involved in the pathogenesis of not only diseases that primarily affect the gastrointestinal tract but also other less obvious diseases, including neurologic, rheumatologic, metabolic, hepatic, and other illnesses. Chronic immune-mediated inflammatory diseases (IMIDs) represent a group of diseases that share many underlying etiological factors including genetics, aberrant immunological responses, and environmental factors. Gut dysbiosis has been reported to be common to IMIDs as a whole, and much effort is currently being directed toward elucidating microbiome-mediated disease mechanisms and their implications for causality. In this review, we discuss gut microbiome studies in several IMIDs and show how these studies can inform our understanding of the role of the gut microbiome in inflammatory bowel disease.
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Microbial balance in the intestinal microbiota and its association with diabetes, obesity and allergic disease.
Gholizadeh, P, Mahallei, M, Pormohammad, A, Varshochi, M, Ganbarov, K, Zeinalzadeh, E, Yousefi, B, Bastami, M, Tanomand, A, Mahmood, SS, et al
Microbial pathogenesis. 2019;:48-55
Abstract
Recent studies have been considered to symbiotic interactions of the human gastrointestinal microbiota and human lifestyle-related disorders. The human gastrointestinal microbiota continuously stimulates the immune system against opportunistic and pathogen bacteria from infancy. Changes in gastrointestinal microbiota have been associated with numbers of human diseases such as allergic diseases, autoimmune encephalitis, atherosclerosis, colorectal cancer, obesity, diabetes etc. In this review article, we evaluate studies on the roles of human gastrointestinal microbiota and interference pathogenicity in allergic diseases, obesity, and diabetes. Several studies indicated association between allergic diseases and changes in bacterial balance such as increased of Clostridium spp., some species of Bifidobacterium spp., or decreased of Bacteroidetes phylum and some species of Bifiobacterium spp. and production of specific short-chain fatty acids due to food type, delivery modes of infant, infant evolvement environment and time of getting bacteria at an early-life age. In addition, obesity and diabetes are associated with food type, production of short chain fatty acids undergo fermentation of the intestinal microbiota, metabolic endotoxemia, endocannabinoid system and properties of the immune system. Well-characterized underlying mechanisms may provide novel strategies for using prebiotic and probiotic to prevent and treatment of allergic diseases, obesity, diabetes, and other lifestyle-related disorders.
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Gut Microbiota Disorder, Gut Epithelial and Blood-Brain Barrier Dysfunctions in Etiopathogenesis of Dementia: Molecular Mechanisms and Signaling Pathways.
Welcome, MO
Neuromolecular medicine. 2019;(3):205-226
Abstract
Emerging evidences indicate a critical role of the gut microbiota in etiopathogenesis of dementia, a debilitating multifactorial disorder characterized by progressive deterioration of cognition and behavior that interferes with the social and professional functions of the sufferer. Available data suggest that gut microbiota disorder that triggers development of dementia is characterized by substantial reduction in specific species belonging to the Firmicutes and Bacteroidetes phyla and presence of pathogenic species, predominantly, pro-inflammatory bacteria of the Proteobacteria phylum. These changes in gut microbiota microecology promote the production of toxic metabolites and pro-inflammatory cytokines, and reduction in beneficial substances such as short chain fatty acids and other anti-inflammatory factors, thereby, enhancing destruction of the gut epithelial barrier with concomitant activation of local and distant immune cells as well as dysregulation of enteric neurons and glia. This subsequently leads to blood-brain barrier dysfunctions that trigger neuroinflammatory reactions and predisposes to apoptotic neuronal and glial cell death, particularly in the hippocampus and cerebral cortex, which underlie the development of dementia. However, the molecular switches that control these processes in the histo-hematic barriers of the gut and brain are not exactly known. This review integrates very recent data on the molecular mechanisms that link gut microbiota disorder to gut epithelial and blood-brain barrier dysfunctions, underlying the development of dementia. The signaling pathways that link gut microbiota disorder with impairment in cognition and behavior are also discussed. The review also highlights potential therapeutic options for dementia.
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Necrotizing Enterocolitis and the Preterm Infant Microbiome.
Baranowski, JR, Claud, EC
Advances in experimental medicine and biology. 2019;:25-36
Abstract
Bacterial colonization patterns in preterm infants differ from those of their term counterparts due to maternal microbial diversity, delivery mode, feeding methods, antibiotic use, and exposure to commensal microbiota and pathogens in the neonatal intensive care unit (NICU). Early gut microbiome dysbiosis predisposes neonates to necrotizing enterocolitis (NEC), a devastating intestinal disease with high morbidity and mortality. Though mechanisms of NEC pathogenesis are not fully understood, the microbiome is a promising therapy target for prevention and treatment. Direct administration of probiotics to preterm infants has been shown to reduce the incidence of NEC, but is not without risk. The immature immune systems of preterm infants leave them vulnerable to even beneficial bacteria. Further research is required to investigate both short-term and long-term effects of probiotic administration to preterm infants. Other methods of altering the preterm infant microbiome must also be considered, including breastfeeding, prebiotics, and targeting the maternal microbiome.