Alterations in the abundance and co-occurrence of Akkermansia muciniphila and Faecalibacterium prausnitzii in the colonic mucosa of inflammatory bowel disease subjects

This work was funded by the Universitat de Girona projects MPCUdG2016-009 and GdRCompetUdG2017, and the Spanish Ministry of Education and Science through projects SAF2006-00414, SAF2010-15896 and SAF2013-43284-P, being the last co-funded by the European Regional Development. Dr. Sylvia H. Duncan acknowledges support from the Scottish Government Research and Environment Science and Analytical Services Division (RESAS).Peer reviewedPublisher PD

Evaluation of bacterial biomarkers to aid in challenging inflammatory bowel diseases diagnostics and subtype classification

Supported by the Spanish Ministry of Education and Science, No. SAF2010-15896, No. SAF2013-43284-P and No. SAF2017-82261-P.Peer reviewedPostprintPublisher PD

The ecology and evolution of the monito del monte, a relict species from the southern South America temperate forests

The arboreal marsupial monito del monte (genus Dromiciops, with two recognized species) is a paradigmatic mammal. It is the sole living representative of the order Microbiotheria, the ancestor lineage of Australian marsupials. Also, this marsupial is the unique frugivorous mammal in the temperate rainforest, being the main seed disperser of several endemic plants of this ecosystem, thus acting as keystone species. Dromiciops is also one of the few hibernating mammals in South America, spending half of the year in a physiological dormancy where metabolism is reduced to 10% of normal levels. This capacity to reduce energy expenditure in winter contrasts with the enormous energy turnover rate they experience in spring and summer. The unique life history strategies of this living Microbiotheria, characterized by an alternation of life in the slow and fast lanes, putatively represent ancestral traits that permitted these cold-adapted mammals to survive in this environment. Here, we describe the ecological role of this emblematic marsupial, summarizing the ecophysiology of hibernation and sociality, updated phylogeographic relationships, reproductive cycle, trophic relationships, mutualisms, conservation, and threats. This marsupial shows high densities, despite presenting slow reproductive rates, a paradox explained by the unique characteristics of its three-dimensional habitat. We finally suggest immediate actions to protect these species that may be threatened in the near future due to habitat destruction and climate change.Fil: Fontúrbel, Francisco E.. Pontificia Universidad Católica de Valparaíso; ChileFil: Franco, Lida M.. Universidad de Ibagué; ColombiaFil: Bozinovic, Francisco. Pontificia Universidad Católica de Chile; ChileFil: Quintero Galvis, Julian F.. Universidad Austral de Chile; ChileFil: Mejías, Carlos. Universidad Austral de Chile; ChileFil: Amico, Guillermo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Vazquez, Miriam Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Sabat, Pablo. Universidad de Chile; ChileFil: Sánchez Hernández, Juan C.. Universidad de Castilla-La Mancha; EspañaFil: Watson, David M.. Charles Sturt University; AustraliaFil: Saenz Agudelo, Pablo. Universidad Austral de Chile; ChileFil: Nespolo, Roberto F.. Universidad Austral de Chile; Chil

Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Prevalence, Abundance, and Virulence of Adherent-Invasive Escherichia coli in Ulcerative Colitis, Colorectal Cancer, and Coeliac Disease

Adherent-invasive E. coli (AIEC) has largely been implicated in the pathogenesis of Crohn's disease (CD). E. coli strains with similar genetic backgrounds and virulence genes profiles have been associated with other intestinal disorders, such as ulcerative colitis (UC), colorectal cancer (CRC), and coeliac disease (CeD), but the role of AIEC in these diseases remains unexplored. We aimed to assess the distribution, abundance, and pathogenic features of AIEC in UC, CRC, and CeD.This work was funded by the Spanish Ministry of Education and Science through projects SAF2010-15896, SAF2013-43284-P, and SAF2107-82261-P (MINECO/AEI/FEDER/UE) and the grant AGL2017-88801-P from the Spanish Ministry of Science and Innovation (MICINN, Spain). MLS is a Serra Húnter Fellow.Peer reviewedSAF2010-15896, SAF2013-43284-P, and SAF2107-82261-P (MINECO/AEI/FEDER/UE) and the grant AGL2017-88801-

Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

BACKGROUND:There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. METHODS:CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. RESULTS:The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. CONCLUSIONS:Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis

Receiver operator characteristic (ROC) curve for diagnosis of pancreatic cancer versus chronic pancreatitis.

<p>Diagnostic performance of CA 19–9, IGF-1 and albumin combination (dotted line) compared with CA 19–9 alone (solid line).</p

Scatter dot plots of serum levels of CA 19–9, CEA, albumin, C-reactive protein, IFG-1 and IGFBP3 in non-jaundiced and jaundiced pancreatic ductal adenocarcinoma (PDAC 1 andPDAC2, respectively), chronic pancreatitis (CP) and healthy control (HC) groups.

<p>The values of individual sera are represented with dots. The center line in the box represents the median, and the top (Q3) and bottom (Q1), the 75^th and 25^th percentiles, respectively.</p