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1.
Nutrients ; 13(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34371976

RESUMO

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (LFD) improves both gastrointestinal (GI) symptoms and the psychological profile of patients with irritable bowel syndrome with diarrhea (IBS-D). The effects of 12 weeks of LFD on GI symptom and psychological profiles in relation to inflammation and the involvement of the intestinal barrier were studied in twenty IBS-D patients. The IBS Severity Scoring System, the Symptom Checklist-90-Revised, the Italian version of the 36-Item Short-Form Health Survey, the IBS-Quality of Life (QoL) questionnaire, and the Psychophysiological questionnaire were administered. The GI barrier function was assessed by sugar absorption test, the serum and fecal zonulin levels, and the serum levels of intestinal fatty-acid binding protein and diamine oxidase. Interleukins (ILs) and lipopolysaccharide (LPS) serum levels were evaluated along with dysbiosis. At the end of LFD, GI symptoms, psychological state (mainly anxiety, somatization, psychoticism, and interpersonal sensitivity), and QoL significantly improved in these patients. Simultaneously, an improvement in small intestinal permeability and intestinal mucosal integrity occurred, while IL-6, Il-10, LPS, and fermentative dysbiosis significantly decreased. The LFD can modify the immune-inflammatory features and enhance intestinal permeability and mucosal integrity, thus determining a concurrent improvement in the clinical and psychological conditions.


Assuntos
Dieta com Restrição de Carboidratos , Fermentação , Trato Gastrointestinal/fisiopatologia , Intestinos/fisiopatologia , Síndrome do Intestino Irritável/dietoterapia , Síndrome do Intestino Irritável/psicologia , Adulto , Diarreia/fisiopatologia , Dissacarídeos , Feminino , Humanos , Inflamação/fisiopatologia , Absorção Intestinal/fisiologia , Mucosa Intestinal/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Monossacarídeos , Oligossacarídeos , Polímeros/administração & dosagem , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
2.
J Clin Invest ; 131(13)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196310

RESUMO

The gut-brain axis (GBA) refers to the complex interactions between the gut microbiota and the nervous, immune, and endocrine systems, together linking brain and gut functions. Perturbations of the GBA have been reported in people with multiple sclerosis (pwMS), suggesting a possible role in disease pathogenesis and making it a potential therapeutic target. While research in the area is still in its infancy, a number of studies revealed that pwMS are more likely to exhibit altered microbiota, altered levels of short chain fatty acids and secondary bile products, and increased intestinal permeability. However, specific microbes and metabolites identified across studies and cohorts vary greatly. Small clinical and preclinical trials in pwMS and mouse models, in which microbial composition was manipulated through the use of antibiotics, fecal microbiota transplantation, and probiotic supplements, have provided promising outcomes in preventing CNS inflammation. However, results are not always consistent, and large-scale randomized controlled trials are lacking. Herein, we give an overview of how the GBA could contribute to MS pathogenesis, examine the different approaches tested to modulate the GBA, and discuss how they may impact neuroinflammation and demyelination in the CNS.


Assuntos
Microbioma Gastrointestinal , Esclerose Múltipla/terapia , Animais , Autoimunidade , Modelos Animais de Doenças , Disbiose/imunologia , Disbiose/fisiopatologia , Sistema Endócrino/imunologia , Sistema Endócrino/fisiopatologia , Sistema Nervoso Entérico/imunologia , Sistema Nervoso Entérico/microbiologia , Sistema Nervoso Entérico/fisiopatologia , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiopatologia , Modelos Neurológicos , Esclerose Múltipla/etiologia , Esclerose Múltipla/microbiologia , Neuroimunomodulação , Probióticos/uso terapêutico
3.
Cells ; 10(7)2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201851

RESUMO

Recently, the involvement of the nervous system in the pathology of allergic diseases has attracted increasing interest. However, the precise pathophysiological role of enteric neurons in food allergies has not been elucidated. We report the presence of functional high-affinity IgE receptors (FcεRIs) in enteric neurons. FcεRI immunoreactivities were observed in approximately 70% of cholinergic myenteric neurons from choline acetyltransferase-eGFP mice. Furthermore, stimulation by IgE-antigen elevated intracellular Ca2+ concentration in isolated myenteric neurons from normal mice, suggesting that FcεRIs are capable of activating myenteric neurons. Additionally, the morphological investigation revealed that the majority of mucosal mast cells were in close proximity to enteric nerve fibers in the colonic mucosa of food allergy mice. Next, using a newly developed coculture system of isolated myenteric neurons and mucosal-type bone-marrow-derived mast cells (mBMMCs) with a calcium imaging system, we demonstrated that the stimulation of isolated myenteric neurons by veratridine caused the activation of mBMMCs, which was suppressed by the adenosine A3 receptor antagonist MRE 3008F20. Moreover, the expression of the adenosine A3 receptor gene was detected in mBMMCs. Therefore, in conclusion, it is suggested that, through interaction with mucosal mast cells, IgE-antigen-activated myenteric neurons play a pathological role in further exacerbating the pathology of food allergy.


Assuntos
Comunicação Celular , Sistema Nervoso Entérico/fisiopatologia , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/fisiopatologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/fisiopatologia , Mastócitos/imunologia , Neurônios/patologia , Adenosina/farmacologia , Antagonistas do Receptor A3 de Adenosina/farmacologia , Animais , Antígenos/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Comunicação Celular/efeitos dos fármacos , Células Cultivadas , Sistema Nervoso Entérico/efeitos dos fármacos , Sistema Nervoso Entérico/imunologia , Mucosa Intestinal/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Modelos Biológicos , Plexo Mientérico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor A3 de Adenosina/genética , Receptor A3 de Adenosina/metabolismo , Receptores de IgE/metabolismo
4.
PLoS One ; 16(7): e0254280, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34237102

RESUMO

BACKGROUND AND AIM: Psychological stress has been shown to increase intestinal permeability and is associated with the development of gastrointestinal disorders. This study aimed to investigate skydiving as an alternative model to analyse the effect of acute psychological stress on intestinal barrier function. MATERIALS AND METHODS: Twenty healthy subjects participated in a tandem skydive followed by a negative control visit, of which 19 (9 females and 10 males, 25.9 ± 3.7 years) were included in the study. Intestinal permeability was assessed by a multi-sugar urinary recovery test. Sucrose recovery and lactulose/rhamnose ratio in 0-5h urine indicated gastroduodenal and small intestinal permeability, respectively, and sucralose/erythritol ratio in 5-24h urine indicated colonic permeability. Blood samples were taken to assess markers associated with barrier function. This study has been registered at ClinicalTrials.gov (NCT03644979) on August 23, 2018. RESULTS: Skydiving resulted in a significant increase in salivary cortisol levels directly after skydiving compared to the control visit. Cortisol levels were still increased two hours after landing, while cortisol levels before skydiving were not significantly different from the baseline at the control visit. Skydiving did not induce a significant increase in gastroduodenal, small intestinal or colonic permeability. There was also no significant increase in plasma intestinal and liver fatty acid-binding proteins, suggesting no damage to the enterocytes. DISCUSSION: These results show that the acute intense psychological stress induced by skydiving does not affect intestinal permeability in healthy subjects. Future models aiming to investigate the effect of stress on human intestinal barrier function should consider a more sustained exposure to the psychological stressor.


Assuntos
Colo/fisiopatologia , Mucosa Intestinal/fisiopatologia , Intestino Delgado/fisiopatologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Adulto , Colo/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Gastroenteropatias/metabolismo , Gastroenteropatias/fisiopatologia , Gastroenteropatias/psicologia , Humanos , Hidrocortisona/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Lactulose/metabolismo , Masculino , Permeabilidade , Ramnose/metabolismo , Estresse Psicológico/metabolismo
5.
Cell Death Dis ; 12(6): 595, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108447

RESUMO

Intestinal mucosal injuries are directly or indirectly related to many common acute and chronic diseases. Long non-coding RNAs (lncRNAs) are expressed in many diseases, including intestinal mucosal injury. However, the relationship between lncRNAs and intestinal mucosal injury has not been determined. Here, we investigated the functions and mechanisms of action of lncRNA Bmp1 on damaged intestinal mucosa. We found that Bmp1 was increased in damaged intestinal mucosal tissue and Bmp1 overexpression was able to alleviate intestinal mucosal injury. Bmp1 overexpression was found to influence cell proliferation, colony formation, and migration in IEC-6 or HIEC-6 cells. Moreover, miR-128-3p was downregulated after Bmp1 overexpression, and upregulation of miR-128-3p reversed the effects of Bmp1 overexpression in IEC-6 cells. Phf6 was observed to be a target of miR-128-3p. Furthermore, PHF6 overexpression affected IEC-6 cells by activating PI3K/AKT signaling which was mediated by the miR-128-3p/PHF6 axis. In conclusion, Bmp1 was found to promote the expression of PHF6 through the sponge miR-128-3p, activating the PI3K/AKT signaling pathway to promote cell migration and proliferation.


Assuntos
Mucosa Intestinal/fisiopatologia , RNA Longo não Codificante/fisiologia , Cicatrização/genética , Animais , Células Cultivadas , Células HEK293 , Humanos , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Proteínas Repressoras/fisiologia , Transdução de Sinais/genética
6.
Int J Sport Nutr Exerc Metab ; 31(4): 359-368, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039771

RESUMO

Along with digestion and absorption of nutrients, the gastrointestinal epithelium acts as a primary intestinal defense layer, preventing luminal pathogens from entering the circulation. During exercise in the heat, epithelial integrity can become compromised, allowing bacteria and bacterial endotoxins to translocate into circulation, triggering a systemic inflammatory response and exacerbating gastrointestinal damage. While this relationship seems clear in the general population in endurance/ultraendurance exercise, the aim of this systematic review was to evaluate the effect of exercise in the heat on blood markers of gastrointestinal epithelial disturbance in well-trained individuals. Following the 2009 Preferred Reporting Items for Systematic Reviewed and Meta-Analyses guidelines, five electronic databases were searched for appropriate research, and 1,885 studies were identified. Five studies met the inclusion criteria and were subject to full methodological appraisal by two reviewers. Critical appraisal of the studies was conducted using the McMasters Critical Review Form. The studies investigated changes in markers of gastrointestinal damage (intestinal fatty acid-binding protein, endotoxin, and/or lipopolysaccharide-binding protein) following acute exercise in warm to hot conditions (≥ 30 °C) and included trained or well-trained participants with direct comparisons to a control temperate condition (≤ 22 °C). The studies found that prolonged submaximal and strenuous exercise in hot environmental conditions can acutely increase epithelial disturbance compared with exercise in cooler conditions, with disturbances not being clinically relevant. However, trained and well-trained populations appear to tolerate exercise-induced gastrointestinal disturbance in the heat. Whether this is an acquired tolerance related to regular training remains to be investigated.


Assuntos
Atletas , Biomarcadores/sangue , Proteínas de Transporte/sangue , Endotoxinas/sangue , Exercício Físico/fisiologia , Proteínas de Ligação a Ácido Graxo/sangue , Temperatura Alta , Mucosa Intestinal/metabolismo , Glicoproteínas de Membrana/sangue , Proteínas de Fase Aguda , Trato Gastrointestinal/fisiopatologia , Temperatura Alta/efeitos adversos , Humanos , Mucosa Intestinal/fisiopatologia , Consumo de Oxigênio , Esforço Físico
7.
J Clin Invest ; 131(10)2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-33998597

RESUMO

Given the crucial role of the gastrointestinal tract and associated organs in handling nutrient assimilation and metabolism, it has long been known that its communication with the brain is important for the control of ingestive behavior and body weight regulation. It is also clear that gut-brain communication is bidirectional and utilizes both rapid neural and slower humoral mechanisms and pathways. However, progress in understanding these mechanisms and leveraging them for the treatment of obesity and metabolic disease has been hindered by the enormous dimension of the gut mucosa, the complexity of the signaling systems, and lack of specific tools. With the ascent of modern neurobiological technology, our understanding of the role of vagal afferents in gut-brain communication has begun to change. The first function-specific populations of vagal afferents providing nutritional feedback as well as feed-forward signals have been identified with genetics-guided methodology, and it is hoped that extension of the methodology to other neural communication pathways will follow soon. Currently, efficient clinical leveraging of gut-brain communication to treat obesity and metabolic disease is limited to a few gut hormones, but a more complete understanding of function-specific and projection-specific neuronal populations should make it possible to develop selective and more effective neuromodulation approaches.


Assuntos
Encéfalo , Mucosa Intestinal , Obesidade , Transmissão Sináptica , Nervo Vago , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiopatologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/fisiopatologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Nervo Vago/metabolismo , Nervo Vago/fisiopatologia
8.
J Clin Invest ; 131(14)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34032635

RESUMO

BACKGROUNDWeeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in children (MIS-C). Gastrointestinal (GI) symptoms are common in patients with MIS-C, and a severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not been identified to date.METHODSHere, we analyzed biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. Stools were assessed for SARS-CoV-2 by reverse transcription PCR (RT-PCR), and plasma was examined for markers of breakdown of mucosal barrier integrity, including zonulin. Ultrasensitive antigen detection was used to probe for SARS-CoV-2 antigenemia in plasma, and immune responses were characterized. As a proof of concept, we treated a patient with MIS-C with larazotide, a zonulin antagonist, and monitored the effect on antigenemia and the patient's clinical response.RESULTSWe showed that in children with MIS-C, a prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. The patient with MIS-C treated with larazotide had a coinciding decrease in plasma SARS-CoV-2 spike antigen levels and inflammatory markers and a resultant clinical improvement above that achieved with currently available treatments.CONCLUSIONThese mechanistic data on MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children.


Assuntos
COVID-19/etiologia , COVID-19/fisiopatologia , Haptoglobinas/fisiologia , Mucosa Intestinal/fisiopatologia , Precursores de Proteínas/fisiologia , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Adolescente , Antígenos Virais/sangue , Biomarcadores/sangue , COVID-19/virologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Haptoglobinas/antagonistas & inibidores , Humanos , Lactente , Recém-Nascido , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/virologia , Masculino , Oligopeptídeos/farmacologia , Permeabilidade/efeitos dos fármacos , Estudo de Prova de Conceito , Precursores de Proteínas/antagonistas & inibidores , Precursores de Proteínas/sangue , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , Síndrome de Resposta Inflamatória Sistêmica/virologia , Adulto Jovem
9.
Radiat Res ; 196(2): 204-212, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34043805

RESUMO

In the event of a radiological attack or accident, it is more likely that the absorbed radiation dose will be heterogeneous, rather than uniformly distributed throughout the body. This type of uneven dose distribution is known as partial-body irradiation (PBI). Partial exposure of the vital organs, specifically the highly radiosensitive intestines, may cause death, if the injury is significant and the post-exposure recovery is considerably compromised. Here we investigated the recovery rate and extent of recovery from PBI-induced intestinal damage in large animals. Rhesus macaques (Macaca mulatta) were randomly divided into four groups: sham-irradiated (0 Gy), 8 Gy PBI, 11 Gy PBI and 14 Gy PBI. A single dose of ionizing radiation was delivered in the abdominal region using a uniform bilateral anteroposterior and posteroanterior technique. Irradiated animals were scheduled for euthanasia on days 10, 28 or 60 postirradiation, and sham-irradiated animals on day 60. Intestinal structural injuries were assessed via crypt depth, villus height, and mucosal surface length in the four different intestinal regions (duodenum, proximal jejunum, distal jejunum and ileum) using H&E staining. Higher radiation doses corresponded with more injury at 10 days post-PBI and a faster recovery rate. However, at 60 days post-PBI, damage was still evident in all regions of the intestine. The proximal and distal ends (duodenum and ileum, respectively) sustained less damage and recovered more fully than the jejunum.


Assuntos
Duodeno/efeitos da radiação , Íleo/efeitos da radiação , Intestino Delgado/efeitos da radiação , Jejuno/efeitos da radiação , Animais , Duodeno/fisiopatologia , Humanos , Íleo/fisiopatologia , Mucosa Intestinal/fisiopatologia , Mucosa Intestinal/efeitos da radiação , Intestino Delgado/fisiopatologia , Intestinos/fisiopatologia , Intestinos/efeitos da radiação , Jejuno/fisiopatologia , Macaca mulatta/fisiologia , Primatas/fisiologia , Doses de Radiação , Radiação Ionizante , Irradiação Corporal Total
10.
Biomed Res Int ; 2021: 6635452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954188

RESUMO

Objective: The lipopolysaccharide- (LPS-) induced acute intestinal dysfunction model has been widely applied in recent years. Here, our aim was to investigate the effect of triggering receptor expressed on myeloid cells-1 (TREM1) inhibitor in LPS-induced acute intestinal dysfunction. Methods: Male rats were randomly assigned into normal (saline injection), model (LPS and saline injection), and LP17 (LPS and LP17 (a synthetic TREM1 inhibitor) injection) groups. The levels of intestinal TREM1 expression were evaluated by immunohistochemistry and western blot. Intestinal permeability and apoptosis were separately assessed by the lactulose/mannitol (L/M) ratio and TUNEL assay. The levels of soluble TREM1 (sTREM1), TNF-α, IL-6, and IL-1ß were measured in the plasma and intestinal tissues by ELISA. The expression levels of NF-κB, high-mobility group box 1 (HMGB1), and toll-like receptor 4 (TLR-4) were measured with RT-qPCR and western blot. After transfection with si-TREM1 in LPS-induced intestinal epithelium-6 (IEC-6) cells, p-p65 and p-IκBα levels were detected by western blot. Results: LP17-mediated TREM1 inhibition alleviated the intestine tissue damage in rats with LPS-induced acute intestinal dysfunction. LP17 attenuated the LPS-induced increase in sTREM1, TNF-α, IL-6, and IL-1ß levels in the plasma and intestinal tissues. Furthermore, intestine permeability and epithelial cell apoptosis were ameliorated by LP17. LP17 attenuated the LPS-induced increase in the expression of TREM1, HMGB1, TLR-4, and NF-κB in the intestine tissues. In vitro, TREM1 knockdown inactivated the NF-κB signaling in LPS-induced IEC-6 cells. Conclusion: LP17 could ameliorate LPS-induced acute intestinal dysfunction, which was associated with inhibition of intestinal apoptosis and inflammation response.


Assuntos
Apoptose , Inflamação/patologia , Intestinos/patologia , Intestinos/fisiopatologia , Receptor Gatilho 1 Expresso em Células Mieloides/antagonistas & inibidores , Doença Aguda , Animais , Inflamação/complicações , Mucosa Intestinal/patologia , Mucosa Intestinal/fisiopatologia , Lipopolissacarídeos , Masculino , NF-kappa B/metabolismo , Permeabilidade , Ratos Sprague-Dawley , Transdução de Sinais , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo
11.
Food Funct ; 12(9): 4142-4151, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977961

RESUMO

Irritable bowel syndrome (IBS) is a common chronic functional bowel disease, associated with a high risk of depression and anxiety. The brain-gut axis plays an important role in the pathophysiological changes involved in IBS; however, an effective treatment for the same is lacking. The natural compound costunolide (COS) has been shown to exert gastroprotective, enteroprotective, and neuroprotective effects, but its therapeutic effects in IBS are unclear. Our study explored the effect of COS on intestinal dysfunction and depressive behaviour in stress-induced IBS mice. Mice were subjected to chronic unpredictable mild stress to trigger IBS, and some were administered COS. Behavioural tests, histochemical assays, western blotting, and measurement of 5-hydroxytryptamine (5-HT) levels in the colon and hippocampus were applied to monitor the physiological and molecular consequences of COS treatment in IBS mice. COS administration relieved intestinal dysfunction and depression-like behaviours in IBS mice. Improvements in low-grade colon inflammation and intestinal mucosal permeability, inhibition of the activation of mast cells, upregulation of colonic Occludin expression, and downregulation of Claudin 2 expression were also observed. COS was also found to upregulate GluN2A, BDNF, p-ERK1/2, and p-CREB expression and 5-HT levels in hippocampal cells but inhibited 5-HT metabolism. Molecular docking showed that COS could form hydrogen bonds with the serotonin transporter (SERT) to affect the reuptake of 5-HT in the intercellular space. In conclusion, COS alleviates intestinal dysfunction and depressive behaviour in stress-induced IBS mice by inhibiting mast cell activation in the colon and regulating 5-HT metabolism in the central nervous system.


Assuntos
Transtorno Depressivo/tratamento farmacológico , Intestinos/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/psicologia , Mastócitos/imunologia , Serotonina/metabolismo , Sesquiterpenos/farmacologia , Animais , Barreira Hematoencefálica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/metabolismo , Colo/imunologia , Hipocampo/metabolismo , Mucosa Intestinal/fisiopatologia , Síndrome do Intestino Irritável/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade , Receptores de N-Metil-D-Aspartato/metabolismo , Sesquiterpenos/farmacocinética , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico
12.
Medicine (Baltimore) ; 100(21): e25883, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032700

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal (GI) disorders affecting up to 11.5% of the general global population. The brain-gut axis has been shown to play an important role in the pathogenesis of IBS. Several studies confirmed that intrinsic brain abnormalities existed in patients with IBS. But, studies of abnormal regional homogeneity (ReHo) in IBS have reported inconsistent results. The objective of this protocol is to conduct a meta-analysis using the Seed-based d mapping software package to identify the most consistent and replicable findings of ReHo in IBS patients. METHOD: We will search the following three electronic databases: MEDLINE, EMBASE and Web of Science. The primary outcome will include the peak coordinates and effect sizes of differences in ReHo between patients with IBS and healthy controls from each dataset. The secondary outcomes will be the effects of age, illness severity, illness duration, and scanner field strength. The SDM approach was used to conduct voxel-wise meta-analysis. Whole-brain voxel-based jackknife sensitivity analysis was performed to conduct jackknife sensitivity analysis. A random effects model with Q statistics is used to conduct heterogeneity and publication bias between studies and meta-regression analyses were carried out to examine the effects of age, illness severity, illness duration, and scanner field strength. RESULTS: The results of this paper will be submitted to a peer-reviewed journal for publication. CONCLUSION: This research will determine the consistent pattern of alterations in ReHo in IBS patients.


Assuntos
Encéfalo/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Mucosa Intestinal/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Humanos , Metanálise como Assunto , Descanso/fisiologia , Índice de Gravidade de Doença , Revisões Sistemáticas como Assunto
13.
Nutrients ; 13(4)2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920345

RESUMO

Numerous disorders can alter the physiological mechanisms that guarantee proper digestion and absorption of nutrients (macro- and micronutrients), leading to a wide variety of symptoms and nutritional consequences. Malabsorption can be caused by many diseases of the small intestine, as well as by diseases of the pancreas, liver, biliary tract, and stomach. This article provides an overview of pathophysiologic mechanisms that lead to symptoms or complications of maldigestion (defined as the defective intraluminal hydrolysis of nutrients) or malabsorption (defined as defective mucosal absorption), as well as its clinical consequences, including both gastrointestinal symptoms and extraintestinal manifestations and/or laboratory abnormalities. The normal uptake of nutrients, vitamins, and minerals by the gastrointestinal tract (GI) requires several steps, each of which can be compromised in disease. This article will first describe the mechanisms that lead to poor assimilation of nutrients, and secondly discuss the symptoms and nutritional consequences of each specific disorder. The clinician must be aware that many malabsorptive disorders are manifested by subtle disorders, even without gastrointestinal symptoms (for example, anemia, osteoporosis, or infertility in celiac disease), so the index of suspicion must be high to recognize the underlying diseases in time.


Assuntos
Mucosa Intestinal/fisiopatologia , Intestino Grosso/fisiopatologia , Intestino Delgado/fisiopatologia , Síndromes de Malabsorção/fisiopatologia , Nutrientes/metabolismo , Anemia/diagnóstico , Anemia/etiologia , Anemia/prevenção & controle , Humanos , Infertilidade/diagnóstico , Infertilidade/etiologia , Infertilidade/prevenção & controle , Absorção Intestinal/fisiologia , Mucosa Intestinal/diagnóstico por imagem , Intestino Grosso/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Síndromes de Malabsorção/complicações , Síndromes de Malabsorção/diagnóstico , Síndromes de Malabsorção/terapia , Osteoporose/diagnóstico , Osteoporose/etiologia , Osteoporose/prevenção & controle
14.
Int J Mol Sci ; 22(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805299

RESUMO

BACKGROUND: Adherent-invasive Escherichia coli (AIEC) have been implicated in the etiology of Crohn's disease. The AIEC reference strain LF82 possesses a pathogenicity island similar to the high pathogenicity island of Yersinia spp., which encodes the yersiniabactin siderophore required for iron uptake and growth of the bacteria in iron-restricted environment. Here, we investigated the role of yersiniabactin during AIEC infection. METHODS: Intestinal epithelial T84 cells and CEABAC10 transgenic mice were infected with LF82 or its mutants deficient in yersiniabactin expression. Autophagy was assessed by Western blot analysis for p62 and LC3-II expression. RESULTS: Loss of yersiniabactin decreased the growth of LF82 in competitive conditions, reducing the ability of LF82 to adhere to and invade T84 cells and to colonize the intestinal tract of CEABAC10 mice. However, yersiniabactin deficiency increased LF82 intracellular replication. Mechanistically, a functional yersiniabactin is necessary for LF82-induced expression of HIF-1α, which is implicated in autophagy activation in infected cells. CONCLUSION: Our study highlights a novel role for yersiniabactin siderophore in AIEC-host interaction. Indeed, yersiniabactin, which is an advantage for AIEC to growth in a competitive environment, could be a disadvantage for the bacteria as it activates autophagy, a key host defense mechanism, leading to bacterial clearance.


Assuntos
Autofagia , Doença de Crohn/etiologia , Infecções por Escherichia coli/complicações , Escherichia coli/patogenicidade , Mucosa Intestinal/fisiopatologia , Fenóis/metabolismo , Tiazóis/metabolismo , Animais , Doença de Crohn/fisiopatologia , Escherichia coli/metabolismo , Infecções por Escherichia coli/fisiopatologia , Masculino , Camundongos , Camundongos Transgênicos
15.
Biochem J ; 478(5): 975-995, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33661278

RESUMO

Dietary nutrients absorbed in the proximal small intestine and assimilated in different tissues have a profound effect on overall energy homeostasis, determined by a balance between body's energy intake and expenditure. In obesity, altered intestinal absorption and consequently tissue assimilation of nutrients may disturb the energy balance leading to metabolic abnormalities at the cellular level. The absorption of nutrients such as sugars, amino acids and fatty acids released from food digestion require high-capacity transporter proteins expressed in the intestinal epithelial absorptive cells. Furthermore, nutrient sensing by specific transporters/receptors expressed in the epithelial enteroendocrine cells triggers release of gut hormones involved in regulating energy homeostasis via their effects on appetite and food intake. Therefore, the intestinal epithelial cells play a pivotal role in the pathophysiology of obesity and associated complications. Over the past decade, gut microbiota has emerged as a key factor contributing to obesity via its effects on digestion and absorption of nutrients in the small intestine, and energy harvest from dietary fiber, undigested component of food, in the large intestine. Various mechanisms of microbiota effects on obesity have been implicated. However, the impact of obesity-associated microbiota on the intestinal nutrient transporters needs extensive investigation. This review marshals the limited studies addressing the altered structure and function of the gut epithelium in obesity with special emphasis on nutrient transporters and role of diet and microbiota. The review also discusses the thoughts and controversies and research gaps in this field.


Assuntos
Dieta , Mucosa Intestinal/fisiopatologia , Microbiota , Nutrientes/metabolismo , Obesidade/patologia , Animais , Humanos , Obesidade/etiologia
16.
Carbohydr Polym ; 261: 117876, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766363

RESUMO

Cyclophosphamide (CTX) is a commonly used antitumor drug in clinical practice, and intestinal mucosal injury is one of its main toxic side effects, which seriously affects the treatment tolerance and prognosis of patients. Therefore, the prevention of intestinal mucosal injury is a research hotspot. Studies have shown that polysaccharides can effectively prevent and improve CTX-induced intestinal mucosal injury and immune system disorders. Recent research has elucidated the structure, biological function, and physicochemical properties of polysaccharides that prevent intestinal mucosal injury, and the potential mechanisms whereby they have this effect. In this paper, we review the recent progress made in understanding the effects of polysaccharides on intestinal mucosal injury and their protective mechanism in order to provide a reference for further research on the prevention of intestinal mucosal injury and the mechanisms involved in nutritional intervention.


Assuntos
Produtos Biológicos/farmacologia , Ciclofosfamida/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antineoplásicos/efeitos adversos , Produtos Biológicos/química , Humanos , Mucosa Intestinal/lesões , Mucosa Intestinal/patologia , Mucosa Intestinal/fisiopatologia , Polissacarídeos/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos
17.
Pediatr Surg Int ; 37(3): 347-352, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33580271

RESUMO

PURPOSE: Monitoring disease progression is crucial to improve the outcome of necrotizing enterocolitis (NEC). A previous study indicates that intestinal wall flow velocity was reduced in NEC pups from the initial stages of the disease. This study aims to investigate whether splanchnic perfusion via the superior mesenteric artery (SMA) (i) is altered during NEC development and (ii) can be used as a monitoring tool to assess disease progression. METHODS: NEC was induced in C57BL/6 mice via gavage feeding of formula, hypoxia, and oral lipopolysaccharide, from postnatal day 5 (P5) to P9 (AUP: 32,238). Breastfed littermates served as controls. Doppler ultrasound (U/S) of bowel loops was performed daily. Intestinal wall perfusion was calculated as average flow velocity (mm/s) of multiple abdominal regions. Groups were compared using one-way ANOVA. RESULTS: The SMA flow velocity was not altered during the initial stage of NEC development, but become significantly reduced at P8 when the intestinal disease was more advanced. These changes occurred concomitantly with an increase in heart rate. CONCLUSIONS: NEC is associated with intestinal hypo-perfusion at the periphery and flow in the SMA is reduced during the later stages of disease indicating the presence of intestinal epithelium damage. This study contributes to understanding NEC pathophysiology and illustrates the value of Doppler U/S in monitoring disease progression.


Assuntos
Enterocolite Necrosante/fisiopatologia , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/fisiologia , Ultrassonografia Doppler , Animais , Modelos Animais de Doenças , Frequência Cardíaca , Humanos , Recém-Nascido , Doenças do Recém-Nascido , Mucosa Intestinal/fisiopatologia , Intestinos/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Perfusão
18.
Dig Dis Sci ; 66(12): 4557-4564, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33537921

RESUMO

Collagenous colitis (CC) is associated with non-bloody, watery diarrhea, which is pathophysiologically reasonable because normal colonic absorption (or excretion) of water and electrolytes can be blocked by the abnormally thick collagen layer in CC. However, CC has also been associated with six previous cases of protein-losing enteropathy (PLE), with no pathophysiologic explanation. The colon does not normally absorb (or excrete) amino acids/proteins, which is primarily the function of the small bowel. Collagenous duodenitis (CD) has not been associated with PLE. This work reports a novel case of CD (and CC) associated with PLE; a pathophysiologically reasonable mechanism for CD causing PLE (by the thick collagen layer of CD blocking normal intestinal amino acid absorption); and a novel association of PLE with severe COVID-19 infection (attributed to relative immunosuppression from hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and malnutrition from PLE).


Assuntos
Aminoácidos/metabolismo , COVID-19/etiologia , Colite Colagenosa/complicações , Duodenite/complicações , Duodeno/fisiopatologia , Absorção Intestinal , Mucosa Intestinal/fisiopatologia , Enteropatias Perdedoras de Proteínas/etiologia , Idoso , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Colite Colagenosa/diagnóstico , Colite Colagenosa/fisiopatologia , Colite Colagenosa/terapia , Duodenite/diagnóstico , Duodenite/fisiopatologia , Duodenite/terapia , Duodeno/metabolismo , Feminino , Hidratação , Glucocorticoides/uso terapêutico , Humanos , Mucosa Intestinal/metabolismo , Estado Nutricional , Nutrição Parenteral Total , Enteropatias Perdedoras de Proteínas/diagnóstico , Enteropatias Perdedoras de Proteínas/fisiopatologia , Enteropatias Perdedoras de Proteínas/terapia , Fatores de Risco , Resultado do Tratamento
19.
J Toxicol Sci ; 46(1): 43-55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33408300

RESUMO

Graphene oxide (GO) is one of the most promising nanomaterials used in biomedicine. However, studies about its adverse effects on the intestine in state of inflammation remain limited. This study aimed to explore the underlying effects of GO on intestinal epithelial cells (IECs) in vitro and colitis in vivo. We found that GO could exert toxic effects on NCM460 cells in a dose- and time-dependent manner and promote inflammation. Furthermore, GO caused lysosomal dysfunction and then blockaded autophagy flux. Moreover, pharmacological autophagy inhibitor 3-Methyladenine could reverse GO-induced LC3B and p62 expression levels, reduce expression levels of IL-6, IL-8, TLR4, and CXCL2, and increase the level of IL-10. In vivo, C57BL/6 mice were treated with 2.5% dextran sulfate sodium (DSS) in drinking water for five consecutive days to induce colitis. Then, GO at 60 mg/kg dose was administered through the oral route every two days from day 2 to day 8. These results showed that GO aggravated DSS-induced colitis, characterized by shortening of the colon and severe pathological changes, and induced autophagy. In conclusion, GO caused the abnormal autophagy in IECs and exacerbated DSS-induced colitis in mice. Our research indicated that GO may contribute to the development of intestinal inflammation by inducing IECs autophagy dysfunction.


Assuntos
Autofagia/efeitos dos fármacos , Colite/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Células Epiteliais/fisiologia , Grafite/efeitos adversos , Mucosa Intestinal/fisiopatologia , Nanoestruturas/efeitos adversos , Animais , Células Cultivadas , Colite/patologia , Colo/patologia , Progressão da Doença , Humanos , Inflamação , Mucosa Intestinal/citologia , Camundongos Endogâmicos C57BL
20.
Food Funct ; 12(4): 1569-1579, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33459741

RESUMO

Galactooligosaccharides (GOS) have been identified as beneficial prebiotics for animals and human beings. Most studies have focused on the effect of GOS on the hindgut populated with abundant microbes. However, few research studies have been conducted on the small intestine, and many results are inconsistent due to the purity of GOS, commonly mixed with monosaccharides or lactose. Therefore, pure GOS with definite structures were prepared and used in the present study to evaluate their effects on intestinal barrier function, inflammatory responses and short-chain fatty acids (SCFAs) produced in the colon of mice challenged with lipopolysaccharide (LPS). The results of 1H and 13C nuclear magnetic resonance spectral analyses indicated that the main structures of GOS with a degree of polymerization of 3 (trisaccharide) and 4 (tetrasaccharide) are [ß-Gal-(1 → 6)-ß-Gal(1 → 4)-ß-Glc] and [ß-Gal-(1 → 6)-ß-Gal-(1 → 6)-ß-Gal-(1 → 4)-ß-Glc], respectively. The results of an in vivo study in mice showed that intragastric administration of 0.5 g per kg BW GOS attenuated intestinal barrier damage and inflammatory responses induced by LPS in the jejunum and ileum, as indicated by increasing villus height and villus-to-crypt ratio, up-regulated intestinal tight junction (ZO-1, occludin, and claudin-1) gene expression, and down-regulated pro-inflammatory cytokines such as IL-1ß, IL-6, IFN-γ, and TNF-α gene expression. Nevertheless, the protective effects of GOS on the intestinal barrier are independent of glucagon-like peptide 2. In addition, 0.5 g per kg BW GOS administration promoted the recovery of colonic acetate, propionate, butyrate, and total SCFA production reduced by LPS challenge. The obtained results provide practical evidence that pure GOS can act as protective agents for intestinal health.


Assuntos
Inflamação/metabolismo , Mucosa Intestinal , Oligossacarídeos , Prebióticos , Animais , Peso Corporal/efeitos dos fármacos , Colo/metabolismo , Citocinas/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiopatologia , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Junções Íntimas/metabolismo
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