0
selected
-
1.
[The Role of the Exposome in the Emergence of Chronic Inflammatory Bowel Diseases].
Niess, JH, Kaymak, T, Hruz, P
Therapeutische Umschau. Revue therapeutique. 2019;(5):261-270
Abstract
The Role of the Exposome in the Emergence of Chronic Inflammatory Bowel Diseases Abstract. Inflammatory Bowel Disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions of the gut related to a combination of genetic and environmental factors that impact on normal host-microbe interactions. The gastrointestinal tract is exposed to an overwhelming load of foreign antigens arising from commensal microorganisms, dietary products and occasional pathogens. But these factors explain only a small fraction of disease risk. During the last two decades advances in genomics, epigenomics and understanding of the intestinal microbiota have improved our knowledge in IBD pathogenesis. Although our ability to predict relapses and response to treatment remains limited, the importance of the external environment to modify the risk of IBD and to precipitate relapses in patients with established disease rises. The term 'exposome' is proposed to reflect a life-course of environmental influences beginning in-utero and proceeding right through childhood to adulthood. While the exposome is still a concept which needs practical perspective to enable better patient care, this review highlights important components of environmental contributors to improve our understanding on pathophysiologic mechanisms in IBD.
-
2.
Targeting anti-fibrotic pathways in Crohn's disease - The final frontier?
Ma, C, Jairath, V, Click, B, Hirota, SA, Lu, C, Parker, CE, Rieder, F, ,
Best practice & research. Clinical gastroenterology. 2019;:101603
Abstract
Intestinal fibrosis with stricture formation affects up to half of patients with Crohn's disease (CD), resulting in impaired quality of life, increased risk of surgical intervention, and associated patient morbidity. The underlying pathophysiologic mechansisms responsible for initiating and perpetuating intestinal fibrosis are complex, dynamic, and implicate both inflammation-dependent and independent pathways. Previously thought to be an irreversible complication of long-standing inflammation unresponsive to medical therapy, fibrostenotic CD has been traditionally managed with endoscopic or surgical approaches. However, recent advances in our understanding of the humoral, cellular, and environmental pathways driving intestinal fibrosis has the potential to fundamentally change these management paradigms for CD-related strictures. Furthermore, the promise of fibrosis treatments in other organ systems has encouraged hope that anti-fibrotic treatment approaches for CD may be within reach. Here, we summarize the key breakthroughs in our molecular understanding of intestinal fibrosis, review current medical, endoscopic, and surgical treatment approaches to CD-related strictures, propose future directions for anti-fibrotic therapy in CD, and identify crucial research questions in this field that require additional investigation.
-
3.
Indications of Intestinal Transplantation.
Kahn, AB, Tulla, KA, Tzvetanov, IG
Gastroenterology clinics of North America. 2019;(4):575-583
Abstract
"The intestinal transplantation is reserved for patients with life-threatening complications of permanent intestinal failure or underlying gastrointestinal disease. The choice of the allograft for a particular patient depends on several factors and the presence of concurrent organ failure, and availability of the donor organs, and specialized care. Combined liver and intestinal transplant allows for patients who have parenteral nutrition-associated liver disease a possibility of improved quality of life and nutrition as well as survival. Intestinal transplantation has made giant strides over the past few decades to the present era where current graft survivals are comparable with other solid organ transplants."
-
4.
Signaling from Intestine to the Host: How Bile Acids Regulate Intestinal and Liver Immunity.
Biagioli, M, Carino, A
Handbook of experimental pharmacology. 2019;:95-108
Abstract
Primary bile acids (BAs) are generated in the liver as the end products of cholesterol catabolism; they are then conjugated and accumulated in the gallbladder. After a meal ingestion, BAs are reversed into the duodenum to facilitate the lipid absorption. At the intestinal level, the 95% of BAs are reabsorbed and redirected into enterohepatic circulation; indeed only a small amount of them are then subjected to chemical modifications by the intestinal microbiota, which plays a very important role in the generation of secondary bile acids and in regulating host's metabolism and activity of the immune system. Behind their role in nutrients absorption, bile acids act as signaling molecules, activating several receptors, known as bile acid-activated receptors (BARs), including the farnesoid-X-receptor (FXR) and the G protein-coupled bile acid receptor 1 (GPBAR1 or Takeda G-protein receptor 5). Both receptors appear to contribute to maintain the tolerogenic state of the liver and intestine immunity. In particular, FXR and GPBAR1 are highly expressed in cells of innate immunity including intestinal and liver macrophages, dendritic cells, and natural killer T cells. In this chapter, we provide an overview on mechanisms through which FXR and GPBAR1 modulate the signaling between microbiota and intestinal and liver innate immune system. This overview could help to explain beneficial effects exerted by GPBAR1 and FXR agonists in the treatment of metabolic and immuno-mediated diseases.
-
5.
The Immunomodulatory Properties of Extracellular Vesicles Derived from Probiotics: A Novel Approach for the Management of Gastrointestinal Diseases.
Molina-Tijeras, JA, Gálvez, J, Rodríguez-Cabezas, ME
Nutrients. 2019;(5)
Abstract
Probiotics, included in functional foods, nutritional supplements, or nutraceuticals, exhibit different beneficial effects on gut function. They are extensively used to improve the digestive processes as well as reduce the symptoms and progression of different diseases. Probiotics have shown to improve dysbiosis and modulate the immune response of the host by interacting with different cell types. Probiotics and the host can interact in a direct way, but it is becoming apparent that communication occurs also through extracellular vesicles (EVs) derived from probiotics. EVs are key for bacteria-bacteria and bacteria-host interactions, since they carry a wide variety of components that can modulate different signaling pathways, including those involved in the immune response. Interestingly, EVs are recently starting to be considered as an alternative to probiotics in those cases for which the use of live bacteria could be dangerous, such as immunocompromised individuals or situations where the intestinal barrier is impaired. EVs can spread through the mucus layer and interact with the host, avoiding the risk of sepsis. This review summarizes the existing knowledge about EVs from different probiotic strains, their properties, and their potential use for the prevention or treatment of different gastrointestinal diseases.
-
6.
The role of splanchnic congestion and the intestinal microenvironment in the pathogenesis of advanced heart failure.
Polsinelli, VB, Marteau, L, Shah, SJ
Current opinion in supportive and palliative care. 2019;(1):24-30
-
-
Free full text
-
Abstract
PURPOSE OF REVIEW Right-sided heart failure, which is often present in the setting of advanced heart failure, is associated with cardiac cachexia, the cardiorenal syndrome, and adverse outcomes. Improved understanding of venous congestion of the splanchnic circulation, which may play a key role in the pathogenesis of right-sided heart failure, could lead to novel therapeutics to ameliorate heart failure. Here we provide an overview of right-sided heart failure, splanchnic hemodynamics, fluid homeostasis, and the intestinal microenvironment. We review recent literature to describe pathophysiologic mechanisms and possible therapeutics. RECENT FINDINGS Several possible mechanisms centered around upregulation of sodium-hydrogen exchanger-3 (NHE3) may form a causal link between right ventricular dysfunction, splanchnic congestion, and worsening heart failure. These include an anaerobic environment in enterocytes, resulting in reduced intracellular pH; increased sodium absorption by the gut via NHE3; decreased pH at the intestinal brush border thus altering the gut microbiome profile; increased bacterial synthesis of trimethylamine N-oxide; and decreased bacterial synthesis of short-chain fatty acids causing abnormal intestinal barrier function. SUMMARY Splanchnic congestion in the setting of right-sided heart failure may serve an important role in the pathogenesis of advanced heart failure, and further exploration of these mechanisms may lead to new therapeutic advances.
-
7.
Coeliac disease: beyond genetic susceptibility and gluten. A narrative review.
Pes, GM, Bibbò, S, Dore, MP
Annals of medicine. 2019;(1):1-16
-
-
Free full text
-
Abstract
Coeliac disease (CD) is an immune-mediated disorder triggered by the ingestion of gluten in genetically susceptible individuals. However, only a small proportion of subjects harbouring CD-related genetic risk develop the disease. Among the environmental factors that may influence CD risk, pre- and perinatal factors, delivery methods, parental lifestyle, infant feeding practices, seasonality, dietary factors, drug use, childhood infections and variability in gut microbiota are those most widely studied regarding the risk to develop CD. Although for many of these external factors the exact mechanism of action is unknown, most of them are thought to act by disrupting the intestinal barrier, facilitating contact between potential antigens and the immune system effector cells. Management of CD is relatively easy in patients with a definite diagnosis and requires a strict, lifelong, gluten-free diet. Better knowledge of environmental exposures apart from gluten can facilitate understanding of the pathogenesis of the disorder and the wide heterogeneity of its clinical spectrum. The purpose of this review is to discuss current knowledge on environmental CD risk factors, as well as possible interaction between them, on the grounds of the reliable scientific evidence available. Key messages The risk of developing CD is influenced not only by gluten ingestion but also by a number of environmental factors including childhood infections and variability in gut microbiota, pre- and perinatal factors, infant feeding practices, delivery methods, parental lifestyle, seasonality, dietary factors and drug use, acting mainly by disrupting intestinal permeability. Better knowledge of exposure to these factors can facilitate their identification, and subsequent elimination, in the individual patient.
-
8.
Taming the Beast: Interplay between Gut Small Molecules and Enteric Pathogens.
Kumar, A, Ellermann, M, Sperandio, V
Infection and immunity. 2019;(9)
-
-
Free full text
-
Abstract
The overuse of antibiotics has led to the evolution of drug-resistant bacteria that are becoming increasingly dangerous to human health. According to the Centers for Disease Control and Prevention, antibiotic-resistant bacteria cause at least 2 million illnesses and 23,000 deaths in the United States annually. Traditionally, antibiotics are bactericidal or bacteriostatic agents that place selective pressure on bacteria, leading to the expansion of antibiotic-resistant strains. In addition, antibiotics that are effective against some pathogens can also exacerbate their pathogenesis and may lead to severe progression of the disease. Therefore, alternative strategies are needed to treat antibiotic-resistant bacterial infections. One novel approach is to target bacterial virulence to prevent or limit pathogen colonization, while also minimizing tissue damage and disease comorbidities in the host. This review focuses on the interactions between enteric pathogens and naturally occurring small molecules in the human gut as potential therapeutic targets for antivirulence strategies. Individual small molecules in the intestines modulate enteric pathogen virulence and subsequent intestinal fitness and colonization. Targeted interruption of pathogen sensing of these small molecules could therefore attenuate their virulence. This review highlights the paths of discovery for new classes of antimicrobials that could potentially mitigate the urgent problem of antibiotic resistance.
-
9.
Current status of graft-versus-host disease after intestinal transplantation.
Ganoza, A, Mazariegos, GV, Khanna, A
Current opinion in organ transplantation. 2019;(2):199-206
Abstract
PURPOSE OF REVIEW Over the past decades, visceral transplantation has become the standard of care for patients with irreversible intestinal failure who suffer complications of total parenteral nutrition (TPN). Graft-versus-host disease (GVHD) after solid organ transplantation is a rare but often fatal complication with high mortality. GVHD after intestinal transplantation, given the large lymphoid content of the graft, is more frequent compared with other solid organs. It is a complex condition that may have varied clinical presentations. The therapy of GVHD is multifactorial and has evolved with visceral transplantation. RECENT FINDINGS In recent large series of intestinal transplantation performed in centers around the world, GVHD remained an important cause of death (40-70%). Advances in immunology and current treatment options come from the hematopoietic stem-cell transplantation (HSCT) experience given the high prevalence of GVHD in that patient population. Therapeutic options for GVHD are based on disease classification, overall grading, organs involved, and associated symptoms. SUMMARY Graft-versus-host disease (GVHD) is a serious complication that can occur after solid organ and allogenic HSCT. Intestinal or multivisceral transplantation have the highest incidence of GVHD among all solid organ transplants with very high mortality rates. Increased risk of GVHD is present after multivisceral and liver-included transplants compared with isolated intestinal transplant. Visceral transplantation is the all-encompassing term used for transplant that includes small bowel. It includes isolated small bowel transplant, small bowel/pancreas transplant, liver/small bowel/ pancreas transplant, stomach/pancreas/small bowel (modified multivisceral transplant), and stomach/liver/pancreas/small bowel (multivisceral). Each of these may or may not include the colon as part of the allograft. Steroids remain the first line of treatment along with modulation of the primary immunosuppression. Steroid-refractory patients remain a challenge and, to date, no consensus has been achieved for a single agent second-line therapy. Successful outcome depends on early diagnosis and prompt treatment.
-
10.
Contextual risk factors impacting the colonization and development of the intestinal microbiota: Implications for children in low- and middle-income countries.
Andrews, K, Gonzalez, A
Developmental psychobiology. 2019;(5):714-728
Abstract
Early adversities, such as poverty, maternal stress, and malnutrition, can affect the structure and functioning of the developing brain with implications for biological systems such as the intestinal microbiota. To date, most studies examining the impact of these risk factors on the development and functioning of the intestinal microbiota have primarily been conducted in high-income countries. However, arguably, children in low- and middle-income countries may be at increased risk given cumulative biological and psychosocial adversities during their development. Accumulating evidence in low- and middle-income countries has linked dysbiosis of the intestinal microbiota to child health outcomes such as stunting, malnutrition, and diarrheal diseases characterized by reduced microbial diversity and elevated pathogenic bacteria, which has implications for psychosocial outcomes. This review summarizes empirical findings that highlight the association between risk factors prevalent in low- and middle-income countries and the intestinal microbiota of children. Additionally, we briefly survey the current evidence regarding the effect of nutritional interventions on the microbial composition of children in low- and middle-income countries. We conclude that these empirical studies have the capacity to inform future research investigating the influence of preventive interventions on biological systems by targeting the predominant risk factors faced by children in low- and middle-income countries.