Cancer Risk in Pediatric-Onset Inflammatory Bowel Disease.
Frontiers in pediatrics. 2020;:400
Inflammatory bowel disease (IBD) is a chronic, immune-mediated, non-curable disease. The incidence of IBD appears to have risen over the last few decades especially in the pediatric age group. IBD usually presents with gastrointestinal symptoms, including abdominal pain, diarrhea, and bleeding per rectum but can also be associated with systemic symptoms such as weight loss, fatigue, joint and skin problems, and psychological comorbidities. One major complication is gastrointestinal and extra-intestinal malignancy. This review discusses literature that focuses on cancer risk of pediatric-onset IBD.
Understanding the mechanisms of efficacy of fecal microbiota transplant in treating recurrent Clostridioides difficile infection and beyond: the contribution of gut microbial-derived metabolites.
Gut microbes. 2020;(1):1810531
Fecal microbiota transplant (FMT) is a highly-effective therapy for recurrent Clostridioides difficile infection (rCDI), and shows promise for certain non-CDI indications. However, at present, its mechanisms of efficacy have remained poorly understood. Recent studies by our laboratory have noted the particular key importance of restoration of gut microbe-metabolite interactions in the ability of FMT to treat rCDI, including the impact of FMT upon short chain fatty acid (SCFAs) and bile acid metabolism. This includes a significant impact of these metabolites upon the life cycle of C. difficile directly, along with potential postulated additional benefits, including effects upon host immune response. In this Addendum, we first present an overview of these recent advancements in this field, and then describe additional novel data from our laboratory on the impact of FMT for rCDI upon several gut microbial-derived metabolites which had not previously been implicated as being of relevance.
Exercise Training Reduces Inflammation of Adipose Tissue in the Elderly: Cross-Sectional and Randomized Interventional Trial.
The Journal of clinical endocrinology and metabolism. 2020;(12)
CONTEXT Metabolic disturbances and a pro-inflammatory state associated with aging and obesity may be mitigated by physical activity or nutrition interventions. OBJECTIVE The aim of this study is to assess whether physical fitness/exercise training (ET) alleviates inflammation in adipose tissue (AT), particularly in combination with omega-3 supplementation, and whether changes in AT induced by ET can contribute to an improvement of insulin sensitivity and metabolic health in the elderly. DESIGN, PARTICIPANTS, MAIN OUTCOME MEASURES The effect of physical fitness was determined in cross-sectional comparison of physically active/physically fit (trained) and sedentary/less physically fit (untrained) older women (71 ± 4 years, n = 48); and in double-blind randomized intervention by 4 months of ET with or without omega-3 (Calanus oil) supplementation (n = 55). Physical fitness was evaluated by spiroergometry (maximum graded exercise test) and senior fitness tests. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Samples of subcutaneous AT were used to analyze mRNA gene expression, cytokine secretion, and immune cell populations. RESULTS Trained women had lower mRNA levels of inflammation and oxidative stress markers, lower relative content of CD36+ macrophages, and higher relative content of γδT-cells in AT when compared with untrained women. Similar effects were recapitulated in response to a 4-month ET intervention. Content of CD36+ cells, γδT-cells, and mRNA expression of several inflammatory and oxidative stress markers correlated to insulin sensitivity and cardiorespiratory fitness. CONCLUSIONS In older women, physical fitness is associated with less inflammation in AT. This may contribute to beneficial metabolic outcomes achieved by ET. When combined with ET, omega-3 supplementation had no additional beneficial effects on AT inflammatory characteristics.
Exercise for Older Adults Improves the Quality of Life in Parkinson's Disease and Potentially Enhances the Immune Response to COVID-19.
Brain sciences. 2020;(9)
Parkinson's disease (PD) is a progressive neurodegenerative disorder brought about due to dopaminergic neuronal cell loss in the midbrain substantia nigra pars compacta region. PD presents most commonly in older adults and is a disorder of both motor and nonmotor dysfunction. The novel SARS-CoV-2 virus is responsible for the recent COVID-19 pandemic, and older individuals, those with preexisting medical conditions, or both have an increased risk of developing COVID-19 with more severe outcomes. People-with-Parkinson's (PwP) of advanced age can have both immune and autonomic nervous problems that potentially lead to pre-existing pulmonary dysfunction and higher infection risk, increasing the probability of contracting COVID-19. A lifestyle change involving moderate-intensity exercise has the potential to protect against SARS-CoV-2 through strengthening the immune system. In addition to a potential protective measure against SARS-CoV-2, exercise has been shown to improve quality-of-life (QoL) in PD patients. Recent studies provide evidence of exercise as both neuroprotective and neuroplastic. This article is a literature review investigating the role exercise plays in modifying the immune system, improving health outcomes in PwP, and potentially acting as a protective measure against SARS-Cov-2 infection. We conclude that exercise, when correctly performed, improves QoL and outcomes in PwP, and that the enhanced immune response from moderate-intensity exercise could potentially offer additional protection against COVID-19.
Metabolic inflammation as an instigator of fibrosis during non-alcoholic fatty liver disease.
World journal of gastroenterology. 2020;(17):1993-2011
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive storage of fatty acids in the form of triglycerides in hepatocytes. It is most prevalent in western countries and includes a wide range of clinical and histopathological findings, namely from simple steatosis to steatohepatitis and fibrosis, which may lead to cirrhosis and hepatocellular cancer. The key event for the transition from steatosis to fibrosis is the activation of quiescent hepatic stellate cells (qHSC) and their differentiation to myofibroblasts. Pattern recognition receptors (PRRs), expressed by a plethora of immune cells, serve as essential components of the innate immune system whose function is to stimulate phagocytosis and mediate inflammation upon binding to them of various molecules released from damaged, apoptotic and necrotic cells. The activation of PRRs on hepatocytes, Kupffer cells, the resident macrophages of the liver, and other immune cells results in the production of proinflammatory cytokines and chemokines, as well as profibrotic factors in the liver microenvironment leading to qHSC activation and subsequent fibrogenesis. Thus, elucidation of the inflammatory pathways associated with the pathogenesis and progression of NAFLD may lead to a better understanding of its pathophysiology and new therapeutic approaches.
Vitamin D and microbiota: Two sides of the same coin in the immunomodulatory aspects.
International immunopharmacology. 2020;:106112
The gut microbiota is crucial for host immune response, vitamin synthesis, short chain fatty acids (SCFAs) production, intestinal permeability, nutrient digestion energy metabolism and protection from pathogens. Therefore, gut microbiota guarantees the host's predisposition to gastrointestinal diseases. Intestinal microbiota may be damaged by environmental components with negative health conditions. Dysbiosis consisting in alteration in the gut microbiota has been involved in several disorders including inflammation, allergic reactions, autoimmune diseases, heart diseases, obesity, and metabolic syndrome and even in the state of malignant carcinogenesis existing in humans. Several epidemiological studies have shown that inadequate solar exposure results in vitamin D insufficiency/deficiency which has a strong impact on different immune responses and the occurrence of a wide range of pathological conditions. Additionally, new evidence indicates that the vitamin D pathway plays a key role in gut homeostasis. Due to the strong connection between vitamin D and microbiota, herein we focus on the new findings about intestinal bacteria-immune crosstalk and the impact of vitamin D in gut microbiota regulation, in order to offer new clarifications on their interaction. Understanding the mechanism by which vitamin D can affect the gut microbiota composition and its dynamic activities, as well as the innate and adaptive state of the immune system, is not only a fundamental research but also an opportunity to improve health status.
What is the collective effect of aging and HIV on the gut microbiome?
Current opinion in HIV and AIDS. 2020;(2):94-100
PURPOSE OF REVIEW Aging and HIV share features of intestinal damage and alterations in the communities of enteric bacteria, termed dysbiosis. The purpose of this review is to highlight the various features of the gut microbiome in aging and in people with HIV (PWH) and to discuss how aging and HIV converge to impact the gut microbiome. The term microbiome reflects the combined genetic material of micro-organisms present including bacteria, viruses, bacteriophages, and fungi. To date, the majority of studies investigating the impact of aging and HIV on the gut microbiome have focused on bacteria, and therefore, for the purposes of this review, the term 'microbiome' is used to reflect enteric bacterial communities. RECENT FINDINGS Aging is associated with alterations in the gut bacterial microbiome. Although changes vary by the age of the population, lifestyle (diet, physical activity) and geographic location, the age-associated dysbiosis is typically characterized by an increase in facultative anaerobes with inflammatory properties and a decrease in obligate anaerobes that play critical roles in maintaining intestinal homeostasis and in regulating host immunity. PWH also have dysbiotic gut microbiomes, many features of which reflect those observed in elderly persons. In one study, the age effect on the gut microbiome differed based on HIV serostatus in older adults. SUMMARY HIV and age may interact to shape the gut microbiome. Future studies should investigate relationships between the gut microbiome and age-associated comorbidities in older PWH populations. Identifying these links will provide new avenues for treatments and interventions to improve the healthspan and lifespan of older PWH.
Seminars in respiratory and critical care medicine. 2020;(1):69-79
Cryptococcosis has become an important infection in both immunocompromised and immunocompetent hosts. Although Cryptococcus is mainly recognized by its ability to cause meningoencephalitis, it can infect almost any organ of the human body, with pulmonary infection being the second most common disease manifestation. In cases of meningitis, symptom onset may be insidious, but headaches, fevers, or mental status changes should warrant diagnostic testing. Symptoms of pulmonary disease are nonspecific and may include fever, chills, cough, malaise, night sweats, dyspnea, weight loss, and hemoptysis. Due to protean manifestations of infection, diagnosis may be delayed or misdiagnosis may occur. Diagnosis typically is made by antigen testing of serum or cerebrospinal fluid or by culture or histopathology of infected tissues. A lumbar puncture with the measurement of opening pressure is recommended for patients with suspected or proven cryptococcosis. Treatment of cryptococcosis is based on the anatomical site of disease, severity of disease, and underlying immune status of the patient. Amphotericin B preparations plus 5-flucytosine is used as initial treatment of meningitis, disseminated infection, or moderate-to-severe pulmonary infection followed by fluconazole as a consolidation therapy. Fluconazole is effective for mild-to-moderate pulmonary infection. Important complications include elevated intracranial pressure and immune reconstitution syndrome, which may resemble active disease.
Gender Differences in Inflammatory Bowel Disease.
Immune-mediated diseases typically show a female preponderance. Looking at all autoimmune diseases combined, 8 of 10 patients are females. Although not as prominent, gender differences in inflammatory bowel disease (IBD) have been reported for epidemiology, disease presentation, disease course and complications, medical and surgical therapies, adherence, psychosocial functioning, and psychiatric co-disorders. While for some factors evidence is rather good, for others data are conflicting. Gastroenterologists dealing with IBD patients in daily clinical practice should be aware of gender-specific issues for the following reasons: (1) misperception of disease presentation potentially delays IBD diagnosis, which has been shown to have deleterious effects, and (2) awareness of gender-specific symptoms and disease severity allows initiation of early and adequately tailored treatment. This might prevent development of complications. And (3) insights into gender-specific differences in terms of treatment and adherence to treatment can improve disease management and foster a more individualized treatment approach. In this review, we summarize current knowledge about gender-specific differences in IBD and highlight the most clinically relevant aspects.
The kynurenine connection: how exercise shifts muscle tryptophan metabolism and affects energy homeostasis, the immune system, and the brain.
American journal of physiology. Cell physiology. 2020;(5):C818-C830
Tryptophan catabolism through the kynurenine pathway generates a variety of bioactive metabolites. Physical exercise can modulate kynurenine pathway metabolism in skeletal muscle and thus change the concentrations of select compounds in peripheral tissues and in the central nervous system. Here we review recent advances in our understanding of how exercise alters tryptophan-kynurenine metabolism in muscle and its subsequent local and distal effects. We propose that the effects of kynurenine pathway metabolites on skeletal muscle, adipose tissue, immune system, and the brain suggest that some of these compounds could qualify as exercise-induced myokines. Indeed, some of the more recently discovered biological activities for kynurenines include many of the best-known benefits of exercise: improved energy homeostasis, promotion of an anti-inflammatory environment, and neuroprotection. Finally, by considering the tissue expression of the different membrane and cytosolic receptors for kynurenines, we discuss known and potential biological activities for these tryptophan metabolites.