A multiomics comparative study on the intervention of fecal microbiota transplants of Fengshining on rheumatoid arthritis / 药学学报

The study aims to investigate the mechanism of Fengshining fecal microbiota transplants in the intervention of rheumatoid arthritis by ultra-performance liquid chromatography-quadrupole/electrostatic field obitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). All animal welfare and experimental procedures followed the regulations of the Medical Ethics Committee of Shanxi University of Chinese medicine. The rats were randomly divided into normal group, model group, fecal microbiota transplantation group and Tripterygium wilfordii polyglycoside group, and the collagen induced arthritis (CIA) was established. The changes of body weight and metatarpodal lesions of rats were evaluated. The serum of rats in each group was analyzed by liquid chromatography-mass spectrometry and metagenomic technology for differential metabolites and microflora. The protein expression levels of Toll-like receptors (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor of kappa B (NF-κB p65) were detected by Western blot. A total of 13 different metabolites, including arachidonic acid, docosahexaenoic acid, 13S-hydroxyoctadecanodienoic acid and L-phenylalanine were screened from serum. Three metabolic pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and arachidonic acid metabolism were identified through pathway enrichment. Metagenomic analysis showed that the abundance of g_Bacteroides, g_Prevotella and p_Actinobacteria in CIA group was higher. The abundance of c_Clostridia, g_Akkermansia and s_Akkermansia_muciniphila in fecal microbiota transplantation group is higher. The hierarchical cluster heat map showed that Akkermansia was negatively correlated with L-phenylalanine; while positively correlated with docosahexaenoic acid. Prevotella was positively correlated with L-phenylalanine. Fecal microbiota transplantation group could significantly inhibit the expression of TLR4, MyD88 and p65 proteins in the synovium of rats (P < 0.01). The anti-rheumatoid arthritis effects of fecal microbiota transplantation group is closely related to the intervention of the metabolism of phenylalanine and arachidonic acid, through Akkermansia, Prevotella and other microorganisms, inhibition the TLR4/MyD88/NF-κB pathway.

Trasplante de microbiota fecal para el tratamiento de la obesidad y de sus comorbilidades asociadas: Revisión

RESUMEN La obesidad es un problema de salud pública a nivel mundial. Existen evidencias sobre la interacción entre la microbiota intestinal, la regulación metabólica y la obesidad. El problema mundial de la obesidad impulsa el estudio de nuevas propuestas preventivas y/o terapéuticas. El trasplante de microbiota fecal (TMF) se proyecta como un posible tratamiento para la obesidad y sus comorbilidades asociadas. El objetivo de este estudio es sintetizar la documentación actual que existe sobre el efecto en parámetros metabólicos y clínicos que produce el TMF en humanos con obesidad, así como evidenciar la metodología empleada en el TMF. En los resultados primarios se señaló la existencia de cambios significativos en la composición de la microbiota intestinal (MI) y mejoría en marcadores metabólicos como disminución de la resistencia a la insulina (RI) y de la hemoglobina glicada (HbA1c), así como aumento de colesterol de alta densidad (HDL). Además, en marcadores clínicos como la disminución del índice de masa corporal y de la circunferencia de cintura. En los resultados secundarios se sustentó la necesidad de estandarizar el diseño experimental del TMF, iniciando con establecer la correcta selección de donantes hasta determinar el seguimiento del TMF a largo plazo. En conclusión, a pesar de que hay un número limitado de estudios y una falta de estandarización de las metodologías para llevar a cabo TMF, se han podido evidenciar algunas asociaciones metabólicas positivas, por lo que el TMF sigue siendo una opción potencialmente prometedora para el tratamiento coadyuvante de la obesidad.

ABSTRACT Obesity is a worldwide health problem. There is evidence of the interaction between the gut microbiota metabolic regulation, and obesity. The global problem of obesity has prompted the study of new preventive and/or therapeutic proposals. Fecal Microbiota Transplantation (FMT) is projected as a possible treatment for obesity and its associated comorbidities. The objective of this study is to synthesize the current documentation that exists on the effect in metabolic and clinical parameters produced by FMT in humans with obesity, as well as to make evident the methodology used in FMT. Primary results indicated the existence of significant changes in the composition of gut microbiota and improvement in some metabolic markers such as a decrease in insulin resistance (IR) and glycated hemoglobin (HbA1c), as well as an increase in high-density cholesterol (HDL). Further changed were noted in clinical markers such as the decrease in body mass index and waist circumference. Secondary results supported the need to standardize the experimental design of FMT, starting with establishing the correct selection of donors to determine the long-term follow-up of FMT. In conclusion, even though there is a limited number of studies and a lack of standardization on the methodology to carry out FMT, some positive metabolic associations have been shown, which is why FMT remains a potentially promising option for treatment adjuvant of obesity.

Efficacy of Fecal Microbiota Transplant in Patients with Moderate or Severe Irritable Bowel Syndrome in India

Background and Aim: To study effect of FMT in patients with moderate or severe IBS. Methods: Patients with IBS for more than one year were offered three sessions of colonoscopicFMT in addition to standard of care. Severity of disease, psychological distress and QOL were assessed by IBS-SSS, HAM-D, HAM-A and WHO-QOL scores. Results: Ten patients with IBS (IBS-D 5, IBS-C 4 and IBS-M 1) were studied. Median IBS-SSS reduced from 313.5 (SD ± 66.8) at baseline to 163 (SD ± 84.5) at 1 week (p = 0.0005), 216 (SD ± 79.3) at 2 weeks (p = 0.003), 201(SD ± 86.6) at 4 weeks (p = 0.005) and 262 (SD ± 69.4) at 8 weeks. Median IBS-SSS at 12 weeks and 24 weeks was not significantly different from baseline. Reduction of IBS-SSS severity was seen in 8 (80%) patients at one week, 6(60%) at 2 and 4 weeks, 3(30%) at 8 weeks and 1(10%) at 12 and 24 weeks. weeks. Of four patients with depression, there was improvement in two patients at 2 and 4 weeks and one at 8 weeks. Quality of life improved in four patients at 2, 4 and 8 weeks, two patients at 12 weeks and one at 24 weeks. Three patients reported marked improvement of symptoms at 12 months along with change in stool odor to donor type. Conclusion: FMT results in short-term improvement in global symptoms of IBS, psychological distress and QOL. Repeat sessions of FMT did not accrue additional benefit.

Trasplante de microbiota fecal / Fecal microbiota's transplant

Introducción: El trasplante de microbiota fecal se basa en la infusión de material fecal de un sujeto sano a otro enfermo por afección específica relacionada con disbiosis de la microbiota intestinal. Entre las indicaciones usadas con resultados promisorios en los últimos 20 años sobresalen infección por Clostridium difficile. Objetivo: Analizar los conocimientos más avanzados y ventajas del trasplante de microbiota fecal en distintas afecciones en el humano, en especial en la infancia. Métodos: Se revisaron las publicaciones sobre esta afección en español e inglés en bases de datos de PubMed, Google Scholar, SciELO y Latindex desde el 2015 hasta el 20 de enero de 2019 Resultados: Se determinan los antecedentes históricos, criterios para indicación del trasplante de microbiota fecal, procedimiento de selección del donante, preparación y conservación de la material fecal, vías de administración, riesgos y efectos adversos, y resultados alcanzados en los últimos años a nivel mundial. Se ha descrito 90 por ciento de resolución de los síntomas en la infección recurrente por Clostridium difficile. Consideraciones finales: El trasplante de microbiota fecal es un tratamiento eficaz y seguro, de fácil realización y buena tolerancia, con repercusión económica y científica, cuya principal indicación aprobada por organizaciones internacionales de la comunidad médica es la infección recurrente o recaída de Clostriium difficile en adultos y niños. Otras indicaciones ensayadas son enfermedades inflamatorias crónicas intestinales, en especial la colitis ulcerosa; síndrome de intestino irritable, enfermedades metabólicas como la obesidad y diabetes mellitus tipo 2 y neuropsiquiátricas que se asocian con desequilibrio de la microbiota intestinal (AU)

Introduction: Fecal microbiota´s transplant (TMF, by its acronym in Spanish) is based on the infusion of fecal material from a healthy subject to another patient due to a specific condition related to intestinal microbiota dysbiosis. Among the indications used with promising results in the last 20 years are the ones used for the infection by Clostridium difficile. Objective: To analyze the most advanced knowledge and advantages of TMF in different conditions in humans, especially in childhood Method: Publications on this condition in Spanish and English in PubMed, Google Scholar, SciELO and Latindex databases from 2015 to January 30, 2019 were reviewed. Results: Historical background, criteria for indication of TMF, donor's selection procedure, preparation and preservation of fecal material, administration routes, risks and adverse effects, and results achieved in recent years worldwide are determined. 90 percent resolution of symptoms in recurrent infection by Clostridium difficile is described. Final considerations: The TMF is an effective and safe treatment, easy to perform and of good tolerance, with economic and scientific impact, whose main indication approved by international organizations of the medical community is the recurrent infection or relapse of Clostriium difficile in adults and children. Other indications tested are chronic intestinal inflammatory diseases, especially ulcerative colitis; irritable bowel syndrome, metabolic diseases as obesity and diabetes mellitus type 2, and neuropsychiatric ones that are associated with imbalance of the intestinal microbiota(AU)

Colitis refractaria por Clostridium difficile tratada con trasplante de microbiota fecal / Refractory colitis by Clostridium difficile treated with fecal microbiota transplant

La diarrea por Clostridium difficile es reconocida de manera creciente en pacientes hospitalizados y se asocia con alta mortalidad. La vancomicina por vía enteral es el tratamiento antibiótico recomendado para las diferentes formas, incluso las más graves. Sin embargo, un grupo pequeño de pacientes desarrolla formas refractarias a ese tratamiento y no existen esquemas antibióticos alternativos recomendados para estos casos. El trasplante de microbiota fecal ha demostrado ser exitoso en una serie de casos de diarrea grave asociada a este microorganismo. Presentamos un caso de diarrea refractaria por C. difficile que fue tratada con éxito con una infusión de microbiota fecal.

Clostridium difficile infection is an increasingly recognized cause of diarrhea in inpatients, frequently associated to high mortality. Vancomycin is the treatment of choice for all Clostridium difficile- associated diarrheas, with different degrees of severity. However, some patients develop refractory forms to that treatment and there are no alternative antibiotic schemes recommended for these cases. Fecal microbiota transplantation has been shown to be successful in a series of cases of severe diarrhea associated with this organism. We present a case of refractory C. difficile infection successfully treated with fecal microbiota transplantation.

Trasplante de microbiota fecal en paciente con colitis ulcerosa e infección refractaria por: revisión de la literatura a partir de un caso clínico / Fecal microbiota transplantation in patient with ulcerative colitis and refractory infection due to: review of the literature based on a clinical case

Infection (CDI) is increasing both in the hospital environment as in the outpatient setting, and is associated with prior use of antibiotics, hospitalizations and inflammatory bowel disease (IBD), among others. It is also characterized by a high rate of recurrence with the usual antibiotic treatment, which increases with greater number of episodes, reaching up to 65 percent. In this context, the transplantation of fecal microbiota (FMT) emerges as recurrent CDI therapy, achieving success rates exceeding 90 percent, including in IBD patients, with minimum rates of recurrence. To achieve such efficiency, the colonization by the donated microbiota in the recipient is critical. The role of FMT is still unclear in IBD therapy not associated with CDI. Although there are great differences in the methodology of FMT, the process has been standardized even creating banks of frozen fecal samples, without reducing its effectiveness. FMT is a safe procedure, without serious adverse events, and accepted by the potential beneficiary population. There are few reported cases of refractory CDI management with FMT. Since 2012, the FMT in CDI and IBD publications have increased significantly, but in our country there are only few reports of this therapeutic strategy. We present a patient with ulcerative colitis and conventional antimicrobial management resistant CDI, which was successfully treated with FMT in a public hospital in Chile.

La infección por Clostridium difficile (ICD) está en aumento tanto en el ambiente hospitalario como ambulatorio, y se asocia a uso previo de antibióticos, hospitalización y enfermedades inflamatorias intestinales (EII), entre otros. Se caracteriza además por su alta tasa de recurrencia con el tratamiento antimicrobiano habitual, que aumenta con el mayor número de episodios alcanzando hasta 65 por ciento. En este contexto, el trasplante de microbiota fecal (TMF) surge como terapia para la ICD recurrente, logrando tasas de éxito superiores a 90 por ciento, incluyendo pacientes con EII, con mínimas tasas de recurrencia. Para lograr esa eficacia, la colonización por la microbiota donada en el receptor es fundamental. Aún no está claro el rol del TMF en la terapia de EII no asociada a ICD. Aunque existe gran heterogeneidad en la metodología del TMF, el proceso se ha ido estandarizando incluso hasta llegar a la creación de bancos de muestra fecal congelada, sin disminuir su efectividad. El TMF es un procedimiento seguro, sin eventos adversos graves y aceptado por la población potencialmente beneficiaria de él. Existen pocos casos publicados de manejo de ICD refractaria con TMF. Desde el 2012 el número de publicaciones sobre TMF en ICD y en EII ha aumentado considerablemente, sin embargo, en nuestro país los reportes sobre esta estrategia terapéutica son escasos. Presentamos el caso de un paciente con colitis ulcerosa e ICD refractaria al manejo antimicrobiano habitual, que se trató exitosamente con TMF en un hospital público de Chile.