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5.
Science ; 368(6487): 186-189, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32273468

RESUMO

Bleeding and altered iron distribution occur in multiple gastrointestinal diseases, but the importance and regulation of these changes remain unclear. We found that hepcidin, the master regulator of systemic iron homeostasis, is required for tissue repair in the mouse intestine after experimental damage. This effect was independent of hepatocyte-derived hepcidin or systemic iron levels. Rather, we identified conventional dendritic cells (cDCs) as a source of hepcidin that is induced by microbial stimulation in mice, prominent in the inflamed intestine of humans, and essential for tissue repair. cDC-derived hepcidin acted on ferroportin-expressing phagocytes to promote local iron sequestration, which regulated the microbiota and consequently facilitated intestinal repair. Collectively, these results identify a pathway whereby cDC-derived hepcidin promotes mucosal healing in the intestine through means of nutritional immunity.


Assuntos
Células Dendríticas/metabolismo , Microbioma Gastrointestinal , Hepcidinas/metabolismo , Enteropatias/microbiologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiologia , Ferro/metabolismo , Animais , Proteínas de Transporte de Cátions/metabolismo , Transplante de Microbiota Fecal , Deleção de Genes , Hepcidinas/genética , Homeostase , Camundongos , Camundongos Mutantes , Fagócitos/metabolismo
7.
Nat Rev Gastroenterol Hepatol ; 17(4): 223-237, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32076145

RESUMO

A key role of the gut microbiota in the establishment and maintenance of health, as well as in the pathogenesis of disease, has been identified over the past two decades. One of the primary modes by which the gut microbiota interacts with the host is by means of metabolites, which are small molecules that are produced as intermediate or end products of microbial metabolism. These metabolites can derive from bacterial metabolism of dietary substrates, modification of host molecules, such as bile acids, or directly from bacteria. Signals from microbial metabolites influence immune maturation, immune homeostasis, host energy metabolism and maintenance of mucosal integrity. Alterations in the composition and function of the microbiota have been described in many studies on IBD. Alterations have also been described in the metabolite profiles of patients with IBD. Furthermore, specific classes of metabolites, notably bile acids, short-chain fatty acids and tryptophan metabolites, have been implicated in the pathogenesis of IBD. This Review aims to define the key classes of microbial-derived metabolites that are altered in IBD, describe the pathophysiological basis of these associations and identify future targets for precision therapeutic modulation.


Assuntos
Microbioma Gastrointestinal/fisiologia , Doenças Inflamatórias Intestinais/microbiologia , Animais , Ácidos e Sais Biliares/metabolismo , Ácidos Graxos Voláteis/fisiologia , Transplante de Microbiota Fecal/métodos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/terapia , Metabolômica/métodos , Probióticos/uso terapêutico , Triptofano/metabolismo
8.
Cell Host Microbe ; 27(2): 169-172, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32053786

RESUMO

Restoration of the gut microbiome is a promising preventive and therapeutic strategy in a number of clinical scenarios. We discuss here the scientific and clinical challenges of engineering and implementing these strategies.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Desenvolvimento de Medicamentos
9.
Actas esp. psiquiatr ; 48(1): 1-7, ene.-feb. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-188327

RESUMO

INTRODUCCIÓN: Durante la última década, se ha obtenido evidencia que respalda la relación entre el microbiota intestinal y el cerebro. El envejecimiento, el estrés, la nutrición y los medicamentos pueden alterar la composición bacteriana de la microbiota intestinal. Esta condición, llamada disbiosis, se puede reparar con prebióticos, probióticos o con trasplante de microbiota fecal (TMF). El TMF es eficaz en el tratamiento de enfermedades inflamatorias intestinales (EII). La información sobre el uso del TMF en los trastornos psiquiátricos es limitada. Este estudio tiene como objetivo investigar los cambios en la severidad de la depresión, la ansiedad y la obsesión de los pacientes que recibieron TMF para el tratamiento de enfermedades inflamatorias intestinales. METODOLOGÍA: Este estudio se realizó con 10 pacientes con EII que se sometieron al TMF entre marzo y septiembre de 2017. El TMF fue realizado por un gastroenterólogo experimentado. Los pacientes completaron el Inventario de Depresión de Beck (IDB), el Listado de Síntomas Revisado (SCL-90-R) y el Inventario Obsesivo-Compulsivo de Maudsley (MOCI) antes del TMF y otra vez un mes después del TMF. RESULTADOS: Se encontraron disminuciones significativas en las puntuaciones del IDB (Z = 2.49, p = 0.013), SCL-90-R (Z = -2.09, p = 0.037) y MOCI (Z = 2.08, p = 0.037) un mes después del TMF. Aunque las puntuaciones de la subescala de ansiedad del SCL-90-R disminuyeron, esta disminución no fue estadísticamente significativa (Z = -1.55, p = 0.121). CONCLUSIONES: La severidad de la ansiedad, la depresión y la obsesión en los pacientes con EII disminuyó después del TMF. La disminución de los síntomas psiquiátricos puede deberse al efecto neuropsiquiátrico directo del TMF (efecto primario), pero también a la mejora de los síntomas gas-trointestinales (efecto secundario). Otra posibilidad es que este resultado sea independiente de estas dos hipótesis. Por lo tanto, los resultados de nuestro estudio no son suficientes para establecer una relación de causa-efecto. Para generalizar estos resultados, se necesitan más ensayos controlados aleatorizados con muestras de más pacientes con ansiedad o depresión, pero sin enfermedades físicas concomitantes


INTRODUCTION: Over the past decade, evidence that supports the relationship between intestinal microbiota and the brain has been obtained. Ageing, stress, nutrition and medi-cines can alter the composition of bacteria in the intestinal microbiota. This condition, called dysbiosis, can be repaired through prebiotics, probiotics or fecal microbiota transplantation (FMT). FMT is effective in the tratamiento of inflammatory bowel diseases (IBD). Information on FMT's use with psychiatric disorders is limited. This study aims to investigate changes in the severity of depression, anxiety and obsession of patients who received FMT for the tratamiento of inflammatory bowel diseases. METHODS: This study was conducted with 10 patients with IBD who underwent FMT between March and September 2017. FMT was performed by an experienced gastroen-terologist. The patients completed the Beck Depression In-ventory (BDI), Symptom Checklist-90-Revised (SCL-90-R) and Maudsley Obsessive Compulsive Inventory (MOCI) be-fore FMT and again at 1 month after FMT. RESULTS: Significant decreases were found in BDI (Z = 2.49, p = 0.013), SCL-90-R (Z = -2.09, p = 0.037) and MOCI (Z = 2.08, p = 0.037) scores after 1 month of FMT. Although he SCL-90-R anxiety subscale scores decreased, this de-crease was not statistically significant (Z = -1.55, p = 0.121). CONCLUSIONS: The severity of anxiety, depression and obsession in IBD patients decreased after FMT. The decrease in psychiatric symptoms may result from the direct neuro-psychiatric effect of FMT (primary effect), but also the im-provement of gastrointestinal symptoms (secondary effect). Another possibility is that this result is independent of these two conditions. Therefore, the results of our study are not sufficient to establish a cause-effect relationship. More ran-domised controlled trials with larger samples from patients with anxiety or depression but without comorbid physical illnesses are needed to generalise these results


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Transtornos de Ansiedade/psicologia , Síndrome do Intestino Irritável/terapia , Constipação Intestinal/terapia , Diarreia/terapia , Transplante de Microbiota Fecal/enfermagem , Fezes/microbiologia , Síndrome do Intestino Irritável/psicologia , Constipação Intestinal/psicologia , Diarreia/psicologia , Gastroenteropatias , Microbioma Gastrointestinal
10.
Am J Gastroenterol ; 115(2): 165-178, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32023228

RESUMO

Small intestinal bacterial overgrowth is defined as the presence of excessive numbers of bacteria in the small bowel, causing gastrointestinal symptoms. This guideline statement evaluates criteria for diagnosis, defines the optimal methods for diagnostic testing, and summarizes treatment options for small intestinal bacterial overgrowth. This guideline provides an evidence-based evaluation of the literature through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the available evidence was not appropriate for a formal GRADE recommendation, key concepts were developed using expert consensus.


Assuntos
Antibacterianos/uso terapêutico , Síndrome da Alça Cega/diagnóstico , Síndrome da Alça Cega/terapia , Dietoterapia , Transplante de Microbiota Fecal , Probióticos/uso terapêutico , Testes Respiratórios , Técnicas de Cultura , Humanos , Hidrogênio/análise , Intestino Delgado , Metano/análise , Sucção
12.
Dtsch Arztebl Int ; 117(3): 31-38, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-32031511

RESUMO

BACKGROUND: Fecal microbiota transfer (FMT) is increasingly being used in Ger- many, as in other countries, for the treatment of recurrent Clostridioides difficile infection (rCDI). FMT is now being performed both for research and in individual patients outside of clinical trials. No compulsory standards have been established to date for donor screening or for the method of fecal transfer. Given the potential dangers of FMT, this would seem to be urgently necessary. METHODS: This review is based on pertinent literature retrieved by a selective search, including the reports of consensus conferences from Germany and abroad. RESULTS: Because of its high efficacy, FMT is the treatment of choice for rCDI. It is largely free of adverse side effects, even in immune-deficient patients, as long as comprehensive and repeated donor screening has been carried out, with extensive clinical and microbiological testing and with the use of structured questionnaires. The ingestion of frozen, encapsulated microbiota is just as effective as other modes of delivery for the treatment of rCDI. CONCLUSION: Encapsulation of the fecal microbiome (FM) and storage at -20°C is the method of choice, because it can be standardized with the necessary quality controls and it is readily available. Patients with rCDI should undergo FMT by orally ingesting the capsules. There are ongoing research efforts to identify the active e FM. It is not yet clear when the ultimate goal of recombinant production can be achieved.


Assuntos
Infecções por Clostridium/terapia , Clostridium difficile , Transplante de Microbiota Fecal , Alemanha , Humanos , Resultado do Tratamento
14.
PLoS One ; 15(1): e0226128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940312

RESUMO

Secondary manifestations of spinal cord injury beyond motor and sensory dysfunction can negatively affect a person's quality of life. Spinal cord injury is associated with an increased incidence of depression and anxiety; however, the mechanisms of this relationship are currently not well understood. Human and animal studies suggest that changes in the composition of the intestinal microbiota (dysbiosis) are associated with mood disorders. The objective of the current study is to establish a model of anxiety following a cervical contusion spinal cord injury in rats and to determine whether the microbiota play a role in the observed behavioural changes. We found that spinal cord injury caused dysbiosis and increased symptoms of anxiety-like behaviour. Treatment with a fecal transplant prevented both spinal cord injury-induced dysbiosis as well as the development of anxiety-like behaviour. These results indicate that an incomplete unilateral cervical spinal cord injury can cause affective disorders and intestinal dysbiosis, and that both can be prevented by treatment with fecal transplant therapy.


Assuntos
Ansiedade/complicações , Ansiedade/prevenção & controle , Comportamento Animal , Disbiose/complicações , Disbiose/prevenção & controle , Transplante de Microbiota Fecal , Traumatismos da Medula Espinal/complicações , Animais , Disbiose/microbiologia , Microbioma Gastrointestinal , Aprendizagem em Labirinto , Ratos , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/microbiologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/psicologia
17.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(1): 44-50, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-31958930

RESUMO

Objective: To summarize the experience of diagnosis and treatment of superior mesenteric artery compression syndrome (SMACS) secondary to chronic constipation according to the concept of Lee's triad syndrome. Methods: The concept of Lee's triad syndrome: (1) clinical symptoms: triad of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, difficulty in eating); (2) anatomical manifestations: with triple anatomy anomaly of transverse colon sagging, elevated spleen flexure, and mesentery arterial compression; (3) treatment: with triple treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation. A descriptive cohort study was performed. According to Lee's triad syndrome criteria, clinical data of 78 patients with superior mesenteric artery compression syndrome secondary to chronic constipation in the Tenth People's Hospital of Tongji University and General Hospital of Eastern Theater Command from June 2004 to November 2018 were prospectively collected, including basic information, symptoms and signs, imaging findings, nutritional indicators, gastrointestinal quality of life index (GIQLI) and Wexner defecation score. The above parameters based on Lee's triad syndrome criteria were followed up and recorded at 1, 3, 6, 12 months after comprehensive treatment. Results: All the patients had Lee's triple symptoms of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, eating difficulties), and triple anatomy anomaly of transverse colon sagging, elevated spleen curvature, and mesentery arterial compression before treatment. After triple treatment of enteral nutrition support, chest-knee posture, and fecal microbiota transplantation, 69 (88.5%) patients had a significant improvement of symptoms, and 9 patients had no significant improvement of symptoms and then eventually received surgery. The 69 cases without operation received follow-up for 12 months. All the patients eventually returned to normal eating, and upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression disappeared. After 1 month, the constipation-related indexes were improved. After 12 months, the number of autonomous defecation per week increased from 1.0±0.8 to 5.0±1.6 (P<0.001). The GIQLI score increased from 52.7±8.5 to 93.2±7.5 (P<0.001), and the Wexner score decreased from 19.1±2.5 to 6.2±2.1 (P<0.001). After 1 month, nutritional indexes were improved gradually. After 12 months, the BMI increased from (17.9±1.8) kg/m(2) to (21.0±1.3) kg/m(2), total protein increased from (65.2±5.7) g/L to (68.3±4.2) g/L, albumin increased from (32.1±5.1) g/L to (40.4±3.0) g/L, prealbumin increased from (163.2±53.7) mg/L to (259.1±45.6) mg/L, fibrinogen increased from (1.9±0.5) g/L to (2.4±0.5) g/L, whose differences were statistically significant (all P<0.001). Upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression were relieved. The angle between superior mesenteric artery and abdominal aorta increased from (17.4±3.8)° to (37.8±5.8)° (t=-22.26, P<0.001). Conclusion: When patients with SMACS secondary to chronic constipation have Lee's triple symptoms and triple anatomy anomaly, the triple combination treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation should be applied.


Assuntos
Constipação Intestinal/complicações , Síndrome da Artéria Mesentérica Superior/diagnóstico , Síndrome da Artéria Mesentérica Superior/terapia , Doença Crônica , Estudos de Coortes , Nutrição Enteral , Transplante de Microbiota Fecal , Humanos , Posição Genupeitoral , Artéria Mesentérica Superior/diagnóstico por imagem , Qualidade de Vida , Síndrome da Artéria Mesentérica Superior/diagnóstico por imagem , Síndrome da Artéria Mesentérica Superior/etiologia , Síndrome , Resultado do Tratamento
20.
Nat Commun ; 11(1): 280, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941900

RESUMO

CrAss-like phages are double-stranded DNA viruses that are prevalent in human gut microbiomes. Here, we analyze gut metagenomic data from mother-infant pairs and patients undergoing fecal microbiota transplantation to evaluate the patterns of acquisition, transmission and strain diversity of crAss-like phages. We find that crAss-like phages are rarely detected at birth but are increasingly prevalent in the infant microbiome after one month of life. We observe nearly identical genomes in 50% of cases where the same crAss-like clade is detected in both the mother and the infant, suggesting vertical transmission. In cases of putative transmission of prototypical crAssphage (p-crAssphage), we find that a subset of strains present in the mother are detected in the infant, and that strain diversity in infants increases with time. Putative tail fiber proteins are enriched for nonsynonymous strain variation compared to other genes, suggesting a potential evolutionary benefit to maintaining strain diversity in specific genes. Finally, we show that p-crAssphage can be acquired through fecal microbiota transplantation.


Assuntos
Bacteriófagos/genética , Fezes/virologia , Microbioma Gastrointestinal/fisiologia , Bacteriófagos/fisiologia , Bacteroides/virologia , Biodiversidade , Cesárea , Transplante de Microbiota Fecal , Feminino , Humanos , Lactente , Metagenoma , Polimorfismo de Nucleotídeo Único , Doadores de Tecidos
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