Special Article
Microbiota and gastrointestinal diseases
Microbiota y enfermedades gastrointestinales
I. Polanco Allué
Departamento de Pediatría, Facultad de Medicina, Universidad Autónoma, Madrid, Spain
Read
6083
Timeswas read the article
2246
Total PDF
3837
Total HTML
Share statistics
array:23 [ "pii" => "S2341287915002781" "issn" => "23412879" "doi" => "10.1016/j.anpede.2015.11.003" "estado" => "S300" "fechaPublicacion" => "2015-12-01" "aid" => "1958" "copyright" => "Asociación Española de Pediatría" "copyrightAnyo" => "2015" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2015;83:443.e1-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1937 "formatos" => array:3 [ "EPUB" => 131 "HTML" => 1324 "PDF" => 482 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S1695403315003598" "issn" => "16954033" "doi" => "10.1016/j.anpedi.2015.07.034" "estado" => "S300" "fechaPublicacion" => "2015-12-01" "aid" => "1958" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2015;83:443.e1-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 14004 "formatos" => array:3 [ "EPUB" => 146 "HTML" => 11839 "PDF" => 2019 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artículo especial</span>" "titulo" => "Microbiota y enfermedades gastrointestinales" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "443.e1" "paginaFinal" => "443.e5" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Microbiota and gastrointestinal diseases" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "I. Polanco Allué" "autores" => array:1 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Polanco Allué" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2341287915002781" "doi" => "10.1016/j.anpede.2015.11.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287915002781?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403315003598?idApp=UINPBA00005H" "url" => "/16954033/0000008300000006/v1_201512060011/S1695403315003598/v1_201512060011/es/main.assets" ] ] "itemAnterior" => array:19 [ "pii" => "S2341287915002811" "issn" => "23412879" "doi" => "10.1016/j.anpede.2015.07.022" "estado" => "S300" "fechaPublicacion" => "2015-12-01" "aid" => "1959" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2015;83:442.e1-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 6681 "formatos" => array:3 [ "EPUB" => 174 "HTML" => 5421 "PDF" => 1086 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special Article</span>" "titulo" => "Congenital anomalies of the kidney and urinary tract. A vision for the paediatrician" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "442.e1" "paginaFinal" => "442.e5" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Anomalías nefrourológicas congénitas. Una visión para el pediatra" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1589 "Ancho" => 2180 "Tamanyo" => 161583 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Factors that influence the progression to chronic renal disease (CRD) in congenital anomalies of the kidney and urinary tract (CAKUT). See text for explanation and details.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.L. Palacios Loro, D.K. Segura Ramírez, F.A. Ordoñez Álvarez, F. Santos Rodríguez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M.L." "apellidos" => "Palacios Loro" ] 1 => array:2 [ "nombre" => "D.K." "apellidos" => "Segura Ramírez" ] 2 => array:2 [ "nombre" => "F.A." "apellidos" => "Ordoñez Álvarez" ] 3 => array:2 [ "nombre" => "F." "apellidos" => "Santos Rodríguez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1695403315003604" "doi" => "10.1016/j.anpedi.2015.07.035" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403315003604?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287915002811?idApp=UINPBA00005H" "url" => "/23412879/0000008300000006/v2_201601190027/S2341287915002811/v2_201601190027/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special Article</span>" "titulo" => "Microbiota and gastrointestinal diseases" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "443.e1" "paginaFinal" => "443.e5" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "I. Polanco Allué" "autores" => array:1 [ 0 => array:3 [ "nombre" => "I." "apellidos" => "Polanco Allué" "email" => array:1 [ 0 => "ipolanco@telefonica.net" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Departamento de Pediatría, Facultad de Medicina, Universidad Autónoma, Madrid, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Microbiota y enfermedades gastrointestinales" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In recent years, extensive efforts have been made in research and clinical practice to gain a more thorough understanding of gut microbiota, its functions, its development, and its role in the pathophysiology of certain diseases.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The human gut is the natural habitat of a numerous, diverse and dynamic population of microorganisms, mainly bacteria that have adapted to live in the mucosal surfaces of the gastrointestinal lumen. The gut microbiota includes native species that colonise the gastrointestinal tract permanently, and a changing series of live microorganisms that pass through the digestive tract on a transient basis. The microbial population of the human gut includes about 100 billion bacteria of 500–1000 different species. The presence of certain bacteria as part of the intestinal flora is necessary for the adequate nutrition and development of the body, as well as for the appropriate maintenance of the immune system. Intestinal homeostasis is critical for the efficient extraction of energy from nutrients and for protection against microbial pathogens. Experiments conducted on mice<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">2</span></a> have demonstrated that germ-free animals are not only smaller than mice that have a normal microbiota from birth or that have been recolonised after being germ-free, but also have less body fat (are leaner); thus, it has been observed that normal-flora or recolonised mice store more fat while eating less. Furthermore, germ-free mice also consume less oxygen.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A thorough knowledge of the gut microbiota is key to determining the role of alterations at this level in the development of certain diseases. Many diseases result, to a great extent, from the presence of an altered intestinal microbiota,<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">3</span></a> such as infectious diarrhoea and diarrhoea associated with antibiotic administration, complications of sepsis (multiple system organ failure, diverticulitis, appendicitis, etc.), functional gastrointestinal disorders (constipation, irritable bowel syndrome, etc.), obesity, diabetes type 2, metabolic syndrome, autoimmune diseases (including celiac disease), or colon cancer.</p><p id="par0020" class="elsevierStylePara elsevierViewall">We proceed to review the main paediatric gastrointestinal diseases that are most strongly associated with the gastrointestinal microbiota. These include infection by <span class="elsevierStyleItalic">Helicobacter pylori</span>, necrotising enterocolitis, inflammatory bowel disease, celiac disease and acute diarrhoea.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Infection by <span class="elsevierStyleItalic">H. pylori</span></span><p id="par0025" class="elsevierStylePara elsevierViewall">More than 50% of the world's population is infected by <span class="elsevierStyleItalic">H. pylori</span>, with a prevalence of 30–40% in developed countries and more than 80% in developing countries.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">4</span></a> In the population under 20 years, the prevalence is approximately 80% in developing countries, higher than in developed countries. The variations in prevalence are associated with sociodemographic factors, especially in individuals of low socioeconomic status.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">While the bacterial load in the stomach is low, <span class="elsevierStyleItalic">Helicobacter</span> species have received special attention due to their association with various gastric diseases. <span class="elsevierStyleItalic">H. pylori</span>, a gram-negative spirochete, is one of the most frequent agents of bacterial infection in humans,<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">6</span></a> and can cause gastritis, gastric and duodenal ulcers, stomach cancer, adenocarcinoma and mucosa-associated lymphoid tissue lymphomas, such as MALT lymphoma.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">7</span></a> In the absence of ulcerative disease, most infections by <span class="elsevierStyleItalic">H. pylori</span> are asymptomatic, and when there are symptoms, they tend to be nonspecific. Recent studies in adults suggest that infection by <span class="elsevierStyleItalic">H. pylori</span> increases the risk of coronary heart disease.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">There is published evidence on the efficacy of lactic acid bacteria, bifidobacteria, fermented milks, <span class="elsevierStyleItalic">Lactobacillus salivarus</span> and <span class="elsevierStyleItalic">Lactobacillus acidophilus</span> for the mitigation of the adverse effects associated with treatment for <span class="elsevierStyleItalic">H. pylori</span> eradication. Several studies have demonstrated the efficacy of some probiotics (such as <span class="elsevierStyleItalic">Saccharomyces boulardii</span> alone or in combination with <span class="elsevierStyleItalic">Lactobacillus casei</span>) for the eradication of <span class="elsevierStyleItalic">H. pylori</span> in paediatric patients.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">9</span></a> There is an even greater volume of evidence in the adult population that supports the recommendation of probiotic therapy for increasing the rate of <span class="elsevierStyleItalic">H. pylori</span> eradication.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">9,10</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Necrotising enterocolitis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Necrotising enterocolitis is the most common gastrointestinal medical emergency that occurs in neonates. It represents a significant clinical problem in infants and affects up to 10% of infants that weigh less than 1500<span class="elsevierStyleHsp" style=""></span>g, especially neonates of extremely low birth weight (<1000<span class="elsevierStyleHsp" style=""></span>g) with less than 28 weeks of gestation.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">11</span></a> Its mortality ranges between 20% and 30% of affected infants. Its morbidity is also high, mainly neurodevelopmental impairment in extremely low birth weight newborns.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">11,12</span></a> Despite advances in neonatal intensive care, NEC continues to be a potentially disastrous disease in preterm newborns, and there have been no significant changes in mortality and long-term morbidity “incidence”.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">12</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Its pathogenesis is poorly known. Several factors may contribute to its development, such as preterm birth, hypoxia, formula feeding, especially excess protein substrate in the intestinal lumen, sepsis, intestinal ischaemia, and colonisation of the gut by pathogenic bacteria.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">11,12</span></a> A recently published study<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">13</span></a> reported a higher proportion of <span class="elsevierStyleItalic">Proteobacteria</span> in newborns that had received a NEC diagnosis, consistent with other evidence. In this study, performed with nine neonates with NEC and nine in the control group, a lower proportion of these bacteria in patients with NEC was observed one week before diagnosis compared to the control group.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">14</span></a> The authors noted that preterm infants not sufficiently colonised by <span class="elsevierStyleItalic">Proteobacteria</span> in the first week of life may not be able to modulate an adaptive immune response against a subsequent bloom of <span class="elsevierStyleItalic">Proteobacteria</span>.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">14</span></a> Therefore, the immaturity of immune tolerance mechanisms, influenced by the quantity and quality of the microbiota, may be related to this disease.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Inflammatory bowel disease</span><p id="par0050" class="elsevierStylePara elsevierViewall">In inflammatory bowel diseases (Crohn's disease and ulcerative colitis) there is an anomalous immune response to elements of the microbiota in the intestinal mucosa that causes intestinal damage.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">15</span></a> In the presence of commensal microorganisms, patients with inflammatory bowel disease show an increase in IgG antibodies and T cell activity in the mucosa, which suggests the suppression of local tolerance mechanisms.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">16</span></a> In fact, there are several factors that influence the stimulation and remission of inflammatory activity, such as derivation of the faecal stream, and the use of antibiotics to treat Crohn's disease and of broad-spectrum antibiotics in the intestinal lumen to treat ulcerative colitis.<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">17,18</span></a> Considering that Crohn's disease in humans occurs in the colon and terminal ileum, where the bacterial concentration is highest,<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">16</span></a> it is fair to assume that the intolerance generated by the microbiota combined with genetic susceptibility would contribute to the development of this inflammatory condition.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">15</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The intestinal lamina propria is the site where immune cells first recognise bacterial antigens prior to their migration to distal lymphoid tissue to mount the inflammatory response.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">19</span></a> Toll-like receptors in epithelial cells and NOD2 receptors play an important role in the induction of the immune response. Once activated, these receptors can trigger an intracellular cascade leading to the production of proinflammatory cytokines.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">20</span></a> This mechanism promotes the maturation of mucosal dendritic cells, which migrate to local lymphoid structures such as Peyer's patches and mesenteric draining lymph nodes following antigen recognition to initiate or maintain T- and B-cell immune responses. Dendritic cells initiate the immune response, control intestinal inflammation and maintain immune tolerance. In this context, it is believed that mucosal dendritic cells play a key role in the modulation of the immune response against the gastrointestinal antigenic environment, maintaining intestinal homeostasis and allowing the peaceful coexistence with the endogenous microflora.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">19</span></a> In normal individuals, the commensal flora cannot cross the epithelial barrier, and when some of these bacteria get through the intestinal barrier, they are quickly phagocytosed by the macrophages in the mucosa, preventing the activation of the intestinal immune response. On the other hand, when pathogenic microorganisms cross the barrier, the immune response is activated.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">21</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Ulcerative colitis and Crohn's disease usually develop in areas with the highest concentrations of gut microbiota, which suggests that commensal bacteria, when associated with genetic susceptibility, may contribute to the pathogenesis of these diseases.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">22</span></a> Furthermore, various studies cited by Danese<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">23</span></a> suggest that the microbiota found in patients with inflammatory bowel disease is different from that of healthy individuals, and the authors noted that dysbiosis may lead to immune intolerance. These patients had a reduced microbial diversity with a predominance of <span class="elsevierStyleItalic">Clostridium</span>, <span class="elsevierStyleItalic">Bacteroides</span> and <span class="elsevierStyleItalic">Bifidobacteria</span> (commensal microbiota) and a concomitant increase in pathogenic bacteria such as <span class="elsevierStyleItalic">Escherichia coli</span>, which is rarely found in individuals without bowel inflammation.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">23</span></a> The proportion of pathogenic bacteria may amount to 30–40% of the predominant bacteria, although it is well known that causality has not been properly established.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">24</span></a> It is worth mentioning that reduced bacterial diversity has been associated with a lack of stability in the microbiota, making it more susceptible to changes in composition driven by environmental factors. Thus, changes in the microbiota may increase the risk of inflammation.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Celiac disease</span><p id="par0065" class="elsevierStylePara elsevierViewall">Celiac disease (CD) is currently defined as an immune-mediated systemic disorder elicited by gluten ingestion in genetically susceptible individuals and characterised by the presence of a variable combination of gluten-dependent clinical manifestations, CD-specific antibodies, HLA DQ2 or DQ8 haplotypes and enteropathy.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">13</span></a> The exclusion of gluten from the diet is associated with the disappearance of the symptoms and the CD-specific antibodies and the normalisation of the intestinal mucosa in most of the patients.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">25</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Studies conducted in recent years have found a prevalence of CD of 1:100 (range, 0.5–2%). The disease affects children as well as adults, and the female to male ratio is 2:1.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In celiac patients, the immune response to gliadin fragments elicits an inflammatory response, mainly in the upper portion of the small intestine, characterised by infiltration of the lamina propria and the epithelium by inflammatory cells and villous atrophy. This response is mediated by innate and adaptive immunity. The adaptive response is mediated by T CD4+ lymphocytes in the lamina propria that recognise gliadin peptides, which bind class II HLA molecules (DQ2 or DQ8) expressed in antigen-presenting cells; T cells then produce proinflammatory cytokines, and interferon γ in particular. The enzyme tissue transglutaminase catalyses the deamidation of gliadin peptides in the intestine, enhancing their immunogenicity.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">25</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">It is believed that besides immunologic and genetic factors, environmental factors such as type of feeding during infancy and the intestinal microbiota play a role in the aetiopathogenesis of CD.<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">26,27</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The importance of the microbiota in CD remains to be determined.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">28</span></a> Some genetic factors have been associated with colonisation by <span class="elsevierStyleItalic">Bacteroides</span> species.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">29</span></a> Some studies conducted on celiac patients have shown that a strict gluten-free diet promotes a decrease in colonisation by beneficial bacteria, especially <span class="elsevierStyleItalic">Bifidobacterium</span> and <span class="elsevierStyleItalic">Lactobacillus</span>, compared to colonisation by gram-negative bacteria (<span class="elsevierStyleItalic">Bacteroides</span> and <span class="elsevierStyleItalic">E. coli</span>).<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">30</span></a> This change in the microbiota following gluten exclusion may be due to the elimination of important sources of carbohydrates, the main source of energy for the commensal microbiota.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">29</span></a> Dietary treatment in these patients does not promote intestinal homeostasis; however, the immunosuppressive effects of such a microbiota may be beneficial for patients with CD.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">31</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Ongoing research on the roles of specific components of the microbiota in the pathogenesis of CD may allow the future development of nutritional intervention strategies (probiotics and prebiotics) for preventive or therapeutic purposes.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Acute diarrhoea</span><p id="par0095" class="elsevierStylePara elsevierViewall">Acute gastroenteritis (AGE) is defined as the passage of loose or watery stools three or more times a day and with a duration of less than 14 days, which distinguishes it from chronic diarrhoea, usually of an infectious origin, with the aetiological agent being a microbial pathogen: viruses, bacteria or parasites. It may be accompanied by nausea, vomiting, fever, abdominal pain or dehydration, and it is usually self-limiting.<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">32–34</span></a> In Europe, the incidence of AGE in children less than 3 years of age ranges between 0.5 and 1.9 episodes per year.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">32</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The most common causative agents are <span class="elsevierStyleItalic">Rotavirus</span> and, among bacteria, <span class="elsevierStyleItalic">Campylobacter</span> followed by <span class="elsevierStyleItalic">Salmonella</span>. Parasites such as <span class="elsevierStyleItalic">Giardia lamblia</span> and <span class="elsevierStyleItalic">Cryptosporidium</span> are a rare cause of diarrhoea in healthy children. The predominant causative agents may change with the age of the child: in children younger than one year, <span class="elsevierStyleItalic">Rotavirus</span>, <span class="elsevierStyleItalic">Norovirus</span>, <span class="elsevierStyleItalic">Adenovirus</span> and <span class="elsevierStyleItalic">Salmonella</span> are most common. Between 1 and 4 years, the same pathogens predominate along with <span class="elsevierStyleItalic">Campylobacter</span> and <span class="elsevierStyleItalic">Yersinia</span>. In children older than 5 years, they are <span class="elsevierStyleItalic">Campylobacter</span>, <span class="elsevierStyleItalic">Salmonella</span> and <span class="elsevierStyleItalic">Rotavirus</span>.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">32</span></a> Diarrhoea associated with antibiotic administration is also common, with an incidence of up to 30%.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">35</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In the management of patients with AGE, the initial treatment must include rehydration by means of oral solutions and a rapid replenishment of nutrients. Rehydration with small volumes of oral solution can compensate the loss of water and electrolytes caused by AGE, but it does not have a favourable impact on the duration of diarrhoea nor on the quality and intensity of the bowel movements; it also does not restore the intestinal microbiota that was altered by the infection.</p><p id="par0110" class="elsevierStylePara elsevierViewall">The rationale for the use of probiotics to treat and prevent AGE is based on the modification of the composition of the gut microbiota to prevent the growth of pathogenic enteric strains. It is also believed that probiotics secrete antibacterial substances, competing with pathogens and preventing their adhesion to the intestinal epithelium, and that they have an anti-toxin effect and reverse some of the consequences of infection of the intestinal epithelium, such as secretory changes and neutrophil migration. Used in combination with rehydration therapy, certain probiotics seem to be safe and have clear beneficial effects in the reduction of the duration and frequency of acute infectious diarrhoea.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The effect of probiotics depends on the species and strain used, and the effects of one microorganism cannot be extrapolated to other species or strains.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">32</span></a> The probiotics for which the efficacy has been clearly demonstrated are basically <span class="elsevierStyleItalic">Lactobacillus rhamnosis</span> GG and <span class="elsevierStyleItalic">S. boulardii</span>.<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">36–38</span></a> The effect seems to be dose-dependent, with higher doses being more efficacious. Probiotics are also more useful when they are administered early in the course of diarrhoea.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Final considerations</span><p id="par0120" class="elsevierStylePara elsevierViewall">The microbiota of the human gut constitutes a universe in itself, alive within our bodies, and it has a significant impact in our physiology and pathophysiology.</p><p id="par0125" class="elsevierStylePara elsevierViewall">The main functions carried out by the human gut microbiota, such as metabolic functions (fermentation of nondigestible dietary substrates and endogenous mucus), protective functions (protection against pathogens in a barrier effect) and trophic functions (control of the proliferation and differentiation of epithelial cells), and its role in the development and homeostasis of the immune system, allow us to say that the gut microbiota is a metabolic organ.</p><p id="par0130" class="elsevierStylePara elsevierViewall">A good understanding of the intestinal microbiota is essential to elucidate the role of changes at this level associated with the development of certain intestinal and extraintestinal diseases.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of interest</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres597308" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec612032" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres597307" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec612031" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Infection by H. pylori" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Necrotising enterocolitis" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Inflammatory bowel disease" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Celiac disease" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Acute diarrhoea" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Final considerations" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-07-23" "fechaAceptado" => "2015-07-29" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec612032" "palabras" => array:5 [ 0 => "Microbiota" 1 => "Children" 2 => "Adolescents" 3 => "Gastrointestinal diseases" 4 => "Probiotics" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec612031" "palabras" => array:5 [ 0 => "Microbiota" 1 => "Niños" 2 => "Adolescentes" 3 => "Enfermedades gastrointestinales" 4 => "Probióticos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The bacterial colonisation is established immediately after birth, through direct contact with maternal microbiota, and may be influenced during lactation. There is emerging evidence indicating that quantitative and qualitative changes on gut microbiota contribute to alterations in the mucosal activation of the immune system, leading to intra- or extra-intestinal diseases. A balance between pathogenic and beneficial microbiota throughout childhood and adolescence is important to gastrointestinal health, including protection against pathogens, inhibition of pathogens, nutrient processing (synthesis of vitamin K), stimulation of angiogenesis, and regulation of host fat storage. Probiotics can promote an intentional modulation of intestinal microbiota favouring the health of the host. A review is presented on the modulation of intestinal microbiota on prevention, and adjuvant treatment of some paediatric gastrointestinal diseases.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La colonización bacteriana se establece inmediatamente después del nacimiento, por contacto directo con la microbiota materna, y puede modificarse durante la lactancia. Están apareciendo datos indicativos de que modificaciones cuantitativas y cualitativas de la microbiota intestinal son capaces de estimular cambios en la activación del sistema inmune que pueden conducir a la aparición de enfermedades gastrointestinales o extraintestinales. El equilibrio entre la microbiota patógena y beneficiosa durante la niñez y la adolescencia es importante para la salud gastrointestinal, incluyendo la protección frente a patógenos, la inhibición de patógenos, el procesamiento de nutrientes (síntesis de vitamina K), el estímulo de la angiogénesis y la regulación del almacenamiento de la grasa corporal. También los probióticos pueden modular la microbiota intestinal para favorecer la salud del huésped. Este artículo es una revisión sobre la acción moduladora de la microbiota intestinal en la prevención y el tratamiento coadyuvante de las enfermedades gastrointestinales pediátricas.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Polanco Allué I. Microbiota y enfermedades gastrointestinales. An Pediatr (Barc). 2015;83:443.e1–443.e5.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:38 [ 0 => array:3 [ "identificador" => "bib0195" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immune-microbiota interactions in health and disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N.W. Palm" 1 => "M.R. de Zoete" 2 => "R.A. Flavell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clim.2015.05.014" "Revista" => array:6 [ "tituloSerie" => "Clin Immunol" "fecha" => "2015" "volumen" => "159" "paginaInicial" => "122" "paginaFinal" => "127" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26141651" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0200" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The gut microbiota as an environmental factor that regulates fat storage" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Bäckhed" 1 => "H. Ding" 2 => "T. Wang" 3 => "L.V. Hooper" 4 => "G.Y. Koh" 5 => "A. Nagy" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Proc Natl Acad Sci USA" "fecha" => "2004" "paginaInicial" => "101" "paginaFinal" => "110" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0205" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gastrointestinal microbiota and some children diseases: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T.K. Weber" 1 => "I. Polanco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2012/676585" "Revista" => array:5 [ "tituloSerie" => "Gastroenterol Res Pract" "fecha" => "2012" "volumen" => "2012" "paginaInicial" => "676585" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23197978" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0210" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">Helicobacter pylori</span> in middle ear of children with otitis media with effusion" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.W. Park" 1 => "J.H. Chung" 2 => "H.J. Min" 3 => "K.R. Kim" 4 => "K. Tae" 5 => "S.H. Cho" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chin Med J (Engl)" "fecha" => "2011" "volumen" => "124" "paginaInicial" => "4275" "paginaFinal" => "4278" "itemHostRev" => array:3 [ "pii" => "S1552526012000568" "estado" => "S300" "issn" => "15525260" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0215" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence and incidence of <span class="elsevierStyleItalic">Helicobacter pylori</span> infection in a healthy pediatric population in the Lisbon area" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Oleastro" 1 => "A. Pelerito" 2 => "P. Nogueira" 3 => "J. Benoliel" 4 => "A. Santos" 5 => "J. Cabral" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1523-5378.2011.00858.x" "Revista" => array:6 [ "tituloSerie" => "Helicobacter" "fecha" => "2011" "volumen" => "16" "paginaInicial" => "363" "paginaFinal" => "372" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21923682" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0220" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">Helicobacter pylori</span> infection and childhood" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Mourad-Baars" 1 => "S. Hussey" 2 => "N.L. Jones" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1523-5378.2010.00776.x" "Revista" => array:6 [ "tituloSerie" => "Helicobacter" "fecha" => "2010" "volumen" => "15" "paginaInicial" => "53" "paginaFinal" => "59" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21054654" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0225" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">Helicobacter pylori</span>-negative gastric mucosa-associated lymphoid tissue lymphomas: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "N. Asano" 1 => "K. Iijima" 2 => "T. Koike" 3 => "A. Imatani" 4 => "T. Shimosegawa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v21.i26.8014" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2015" "volumen" => "21" "paginaInicial" => "8014" "paginaFinal" => "8020" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26185372" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0230" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A meta-analysis of the association between <span class="elsevierStyleItalic">Helicobacter pylori</span> infection and risk of coronary heart disease from published prospective studies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Sun" 1 => "P. Rangan" 2 => "S.S. Bhat" 3 => "L. Liu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/hel.12234" "Revista" => array:2 [ "tituloSerie" => "Helicobacter" "fecha" => "2015" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0235" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical efficacy of probiotics: review of the evidence with focus on children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "NASPGHAN Nutrition Report Committee" 1 => "S. Michael" 2 => "F. Silvester" 3 => "G. Fuchs" 4 => "R. Issenman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.mpg.0000239990.35517.bf" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2006" "volumen" => "43" "paginaInicial" => "550" "paginaFinal" => "557" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17033538" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0240" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Probiotics in <span class="elsevierStyleItalic">Helicobacter pylori</span> eradication therapy: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.M. Zhang" 1 => "W. Qian" 2 => "Y.Y. Qin" 3 => "J. He" 4 => "Y.H. Zhou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v21.i14.4345" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2015" "volumen" => "21" "paginaInicial" => "4345" "paginaFinal" => "4357" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25892886" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0245" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Critical systematic review of the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.A. Mihatsch" 1 => "C.P. Braegger" 2 => "T. Decsi" 3 => "S. Kolacek" 4 => "H. Lanzinger" 5 => "B. Mayer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clnu.2011.09.004" "Revista" => array:6 [ "tituloSerie" => "Clin Nutr" "fecha" => "2012" "volumen" => "31" "paginaInicial" => "6" "paginaFinal" => "15" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21996513" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0250" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G. Deshpande" 1 => "S. Rao" 2 => "S. Patole" 3 => "M. Bulsara" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1542/peds.2009-1301" "Revista" => array:6 [ "tituloSerie" => "Pediatrics" "fecha" => "2010" "volumen" => "125" "paginaInicial" => "921" "paginaFinal" => "930" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20403939" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0255" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Husby" 1 => "S. Koletzko" 2 => "I.R. Korponay-Szabó" 3 => "M.L. Mearin" 4 => "A. Phillips" 5 => "R. Shamir" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MPG.0b013e31821a23d0" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2012" "volumen" => "54" "paginaInicial" => "136" "paginaFinal" => "160" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22197856" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0260" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fecal microbiota in premature infants prior to necrotizing enterocolitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Mai" 1 => "C.M. Young" 2 => "M. Ukhanova" 3 => "X. Wang" 4 => "Y. Sun" 5 => "G. Casella" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0020647" "Revista" => array:5 [ "tituloSerie" => "PLoS ONE" "fecha" => "2011" "volumen" => "6" "paginaInicial" => "e20647" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21674011" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0265" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inflammatory bowel disease: immunodiagnostics, immunotherapeutics, and ecotherapeutics" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F. Shanahan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2011" "volumen" => "120" "paginaInicial" => "622" "paginaFinal" => "635" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11179240" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0270" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Innate and adaptive mechanisms to control pathological intestinal inflammation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "B.L. Kelsall" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/path.2286" "Revista" => array:6 [ "tituloSerie" => "J Pathol" "fecha" => "2008" "volumen" => "214" "paginaInicial" => "242" "paginaFinal" => "259" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18161750" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0275" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G.R. D’Haens" 1 => "K. Geboes" 2 => "M. Peeters" 3 => "F. Baert" 4 => "F. Penninckx" 5 => "P. Rutgeerts" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "1998" "volumen" => "114" "paginaInicial" => "262" "paginaFinal" => "267" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9453485" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0280" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.B. Sartor" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2004" "volumen" => "126" "paginaInicial" => "1620" "paginaFinal" => "1633" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15168372" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0285" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of mucosal dendritic cells in inflammatory bowel disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.H. Niess" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2008" "volumen" => "14" "paginaInicial" => "5138" "paginaFinal" => "5148" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18777590" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S155252601200012X" "estado" => "S300" "issn" => "15525260" ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0290" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "War and peace at mucosal surfaces" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.J. Sansonetti" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nri1499" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Immunol" "fecha" => "2004" "volumen" => "4" "paginaInicial" => "953" "paginaFinal" => "964" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15573130" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0295" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.J. Macpherson" 1 => "D. Gatto" 2 => "E. Sainsbury" 3 => "G.R. Harriman" 4 => "H. Hengartner" 5 => "R.M. Zinkernagel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "2000" "volumen" => "288" "paginaInicial" => "2222" "paginaFinal" => "2226" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10864873" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0300" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Microbial influences in inflammatory bowel diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.B. Sartor" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2007.11.059" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2008" "volumen" => "134" "paginaInicial" => "577" "paginaFinal" => "594" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18242222" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0305" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intestinal microbiota in inflammatory bowel disease: friend of foe" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. Danese" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v17.i5.557" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2011" "volumen" => "17" "paginaInicial" => "557" "paginaFinal" => "566" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21350704" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0310" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mucosal colonization with <span class="elsevierStyleItalic">Lactobacillus casei</span> mitigates barriers injury induced by exposure to trinitronbenzene sulfonic acid" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Llopis" 1 => "M. Antolín" 2 => "F. Guarner" 3 => "A. Salas" 4 => "J.R. Malagelada" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.2004.056101" "Revista" => array:6 [ "tituloSerie" => "Gut" "fecha" => "2005" "volumen" => "54" "paginaInicial" => "955" "paginaFinal" => "959" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15951541" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0315" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Celiac disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "I. Polanco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MPG.0b013e3181818df5" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2008" "volumen" => "47" "paginaInicial" => "S3" "paginaFinal" => "S6" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18667915" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0320" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of milk-feeding type and genetic risk of developing coeliac disease on intestinal microbiota of infants: the PROFICEL study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G.D. Palma" 1 => "A. Capilla" 2 => "E. Nova" 3 => "G. Castillejo" 4 => "V. Varea" 5 => "T. Pozo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0030791" "Revista" => array:5 [ "tituloSerie" => "PLoS ONE" "fecha" => "2012" "volumen" => "7" "paginaInicial" => "e30791" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22319588" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0325" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Composition and diversity of the duodenal mucosa-associated microbiome in children with untreated coeliac disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "T. Meij" 1 => "A. Budding" 2 => "M. Grasman" 3 => "F. Kneepkens" 4 => "P. Savelkoul" 5 => "M.L. Mearin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Scand J Gastroenterol" "fecha" => "2013" "paginaInicial" => "530" "paginaFinal" => "536" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0330" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The intestinal microflora of childhood patients with indicated celiac disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. Kopecný" 1 => "J. Mrázek" 2 => "K. Fliegerová" 3 => "P. Frühauf" 4 => "L. Tucková" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Folia Microbiol (Praha)" "fecha" => "2008" "volumen" => "53" "paginaInicial" => "214" "paginaFinal" => "216" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0335" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of environmental and genetic factors linked to celiac disease risk on infant gut colonization by <span class="elsevierStyleItalic">Bacteroides</span> species" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Sánchez" 1 => "G. de Palma" 2 => "A. Capilla" 3 => "E. Nova" 4 => "T. Pozo" 5 => "G. Castillejo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AEM.00365-11" "Revista" => array:6 [ "tituloSerie" => "Appl Environ Microbiol" "fecha" => "2011" "volumen" => "77" "paginaInicial" => "5316" "paginaFinal" => "5323" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21642397" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0340" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imbalance in the composition of the duodenal microbiota of children with coeliac disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "I. Nadal" 1 => "E. Donat" 2 => "C. Ribes-Koninckx" 3 => "M. Calabuig" 4 => "Y. Sanz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1099/jmm.0.47410-0" "Revista" => array:6 [ "tituloSerie" => "J Med Microbiol" "fecha" => "2007" "volumen" => "56" "paginaInicial" => "1669" "paginaFinal" => "1674" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18033837" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0345" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of a gluten-free diet on gut microbiota and immune function in healthy adult humans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Y. Sanz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4161/gmic.1.3.11868" "Revista" => array:6 [ "tituloSerie" => "Gut Microbes" "fecha" => "2010" "volumen" => "1" "paginaInicial" => "135" "paginaFinal" => "137" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21327021" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0350" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases Evidence-Based Guidelines for the Management of Acute Gastroenteritis in Children in Europe: Update 2014" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Guarino" 1 => "S. Ashkenazi" 2 => "D. Gendrel" 3 => "A. Lo Vecchio" 4 => "R. Shamir" 5 => "H. Szajewska" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MPG.0000000000000375" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2014" "volumen" => "59" "paginaInicial" => "132" "paginaFinal" => "152" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24739189" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0355" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guía de práctica clínica gastroenteritis aguda en el niño. Guía multidisciplinar promovida y avalada por la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica y la Sociedad Española de Infectología Pediátrica" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Costa i Pagès" 1 => "I. Polanco Allué" 2 => "C. Rodrigo Gonzalo de Liria" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2010" "editorial" => "Ergon" "editorialLocalizacion" => "Madrid" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0360" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guía práctica clínica iberolatinoamericana sobre el manejo de la gastroenteritis aguda en menores de 5 años: tratamiento farmacológico" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Grupo Ibero-Latinoamericano sobre el Manejo de la Diarrea Aguda (GILA)" "etal" => false "autores" => array:3 [ 0 => "E. Salazar-Lindo" 1 => "I. Polanco Allué" 2 => "P. Gutiérrez-Castrellón" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "An Pediatr (Barc)" "fecha" => "2014" "volumen" => "80" "paginaInicial" => "15" "paginaFinal" => "22" ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0365" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Meta-analysis: non-pathogenic yeast <span class="elsevierStyleItalic">Saccharomyces boulardii</span> in the prevention of antibiotic-associated diarrhoea" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H. Szajewska" 1 => "J. Mrukowicz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2036.2005.02624.x" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2005" "volumen" => "22" "paginaInicial" => "365" "paginaFinal" => "372" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16128673" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0370" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Probiotics and prebiotics in infants and children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "V. Vandenplas" 1 => "E. De Greef" 2 => "T. Devreker" 3 => "G. Veereman-Wauters" 4 => "B. Hauser" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11908-013-0334-4" "Revista" => array:6 [ "tituloSerie" => "Curr Infect Dis Rep" "fecha" => "2013" "volumen" => "15" "paginaInicial" => "251" "paginaFinal" => "262" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23640127" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0375" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Meta-analysis: <span class="elsevierStyleItalic">Saccharomyces boulardii</span> for treating acute diarrhea in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H. Szajewska" 1 => "A. Skorka" 2 => "M. Dylag" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2036.2006.03202.x" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2007" "volumen" => "25" "paginaInicial" => "257" "paginaFinal" => "264" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17269987" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0380" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Probiotics for children with diarrhea: an update" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. Guandalini" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MCG.0b013e3181674087" "Revista" => array:6 [ "tituloSerie" => "J Clin Gastroenterol" "fecha" => "2008" "volumen" => "42" "paginaInicial" => "S53" "paginaFinal" => "S57" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18520336" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000008300000006/v2_201601190027/S2341287915002781/v2_201601190027/en/main.assets" "Apartado" => array:4 [ "identificador" => "46679" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Special Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000008300000006/v2_201601190027/S2341287915002781/v2_201601190027/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287915002781?idApp=UINPBA00005H" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 10 | 17 |
| 2024 October | 60 | 30 | 90 |
| 2024 September | 65 | 43 | 108 |
| 2024 August | 53 | 50 | 103 |
| 2024 July | 59 | 31 | 90 |
| 2024 June | 58 | 41 | 99 |
| 2024 May | 45 | 35 | 80 |
| 2024 April | 59 | 35 | 94 |
| 2024 March | 38 | 22 | 60 |
| 2024 February | 31 | 23 | 54 |
| 2024 January | 38 | 23 | 61 |
| 2023 December | 33 | 14 | 47 |
| 2023 November | 42 | 23 | 65 |
| 2023 October | 39 | 38 | 77 |
| 2023 September | 24 | 22 | 46 |
| 2023 August | 50 | 19 | 69 |
| 2023 July | 32 | 25 | 57 |
| 2023 June | 43 | 31 | 74 |
| 2023 May | 50 | 28 | 78 |
| 2023 April | 37 | 18 | 55 |
| 2023 March | 57 | 28 | 85 |
| 2023 February | 29 | 20 | 49 |
| 2023 January | 18 | 20 | 38 |
| 2022 December | 75 | 31 | 106 |
| 2022 November | 83 | 43 | 126 |
| 2022 October | 57 | 55 | 112 |
| 2022 September | 71 | 32 | 103 |
| 2022 August | 88 | 36 | 124 |
| 2022 July | 78 | 41 | 119 |
| 2022 June | 40 | 45 | 85 |
| 2022 May | 68 | 43 | 111 |
| 2022 April | 34 | 35 | 69 |
| 2022 March | 47 | 53 | 100 |
| 2022 February | 29 | 27 | 56 |
| 2022 January | 24 | 32 | 56 |
| 2021 December | 29 | 32 | 61 |
| 2021 November | 39 | 37 | 76 |
| 2021 October | 49 | 45 | 94 |
| 2021 September | 45 | 48 | 93 |
| 2021 August | 35 | 32 | 67 |
| 2021 July | 21 | 26 | 47 |
| 2021 June | 47 | 37 | 84 |
| 2021 May | 29 | 37 | 66 |
| 2021 April | 104 | 77 | 181 |
| 2021 March | 75 | 24 | 99 |
| 2021 February | 47 | 29 | 76 |
| 2021 January | 34 | 27 | 61 |
| 2020 December | 34 | 24 | 58 |
| 2020 November | 27 | 21 | 48 |
| 2020 October | 17 | 20 | 37 |
| 2020 September | 34 | 20 | 54 |
| 2020 August | 24 | 17 | 41 |
| 2020 July | 23 | 24 | 47 |
| 2020 June | 27 | 13 | 40 |
| 2020 May | 45 | 21 | 66 |
| 2020 April | 18 | 21 | 39 |
| 2020 March | 35 | 21 | 56 |
| 2020 February | 33 | 16 | 49 |
| 2020 January | 22 | 17 | 39 |
| 2019 December | 25 | 21 | 46 |
| 2019 November | 28 | 6 | 34 |
| 2019 October | 20 | 13 | 33 |
| 2019 September | 18 | 10 | 28 |
| 2019 August | 29 | 14 | 43 |
| 2019 July | 49 | 14 | 63 |
| 2019 June | 39 | 20 | 59 |
| 2019 May | 41 | 35 | 76 |
| 2019 April | 54 | 34 | 88 |
| 2019 March | 43 | 17 | 60 |
| 2019 February | 44 | 18 | 62 |
| 2019 January | 38 | 24 | 62 |
| 2018 December | 37 | 25 | 62 |
| 2018 November | 77 | 47 | 124 |
| 2018 October | 129 | 29 | 158 |
| 2018 September | 69 | 21 | 90 |
| 2018 August | 9 | 0 | 9 |
| 2018 July | 11 | 0 | 11 |
| 2018 June | 15 | 0 | 15 |
| 2018 May | 58 | 0 | 58 |
| 2018 April | 22 | 0 | 22 |
| 2018 March | 27 | 0 | 27 |
| 2018 February | 10 | 0 | 10 |
| 2018 January | 14 | 0 | 14 |
| 2017 December | 21 | 0 | 21 |
| 2017 November | 18 | 0 | 18 |
| 2017 October | 25 | 0 | 25 |
| 2017 September | 18 | 0 | 18 |
| 2017 August | 19 | 0 | 19 |
| 2017 July | 24 | 0 | 24 |
| 2017 June | 33 | 21 | 54 |
| 2017 May | 37 | 12 | 49 |
| 2017 April | 17 | 11 | 28 |
| 2017 March | 15 | 7 | 22 |
| 2017 February | 7 | 3 | 10 |
| 2017 January | 10 | 6 | 16 |
| 2016 December | 16 | 9 | 25 |
| 2016 November | 27 | 7 | 34 |
| 2016 October | 29 | 17 | 46 |
| 2016 September | 21 | 8 | 29 |
| 2016 August | 27 | 2 | 29 |
| 2016 July | 13 | 7 | 20 |
Show all
