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Chronic kidney disease (CKD) is a progressive loss of renal function in which gut dysbiosis is involved. Fecal microbiota transplantation (FMT) may be a promising alternative for restoring gut microbiota and treating CKD. This study evaluated the changes in CKD progression in patients treated with FMT. Patients with diabetes and/or hypertension with CKD clinical stages 2, 3, and 4 in this single-center, double-blind, randomized, placebo-controlled clinical trial (NCT04361097) were randomly assigned to receive either FMT or placebo capsules for 6 months. Laboratory and stool metagenomic analyses were performed. A total of 28 patients were included (15 FMT and 13 placebo). Regardless of CKD stages, patients responded similarly to FMT treatment. More patients (53.8%) from the placebo group progressed to CKD than the FMT group (13.3%). The FMT group maintained stable renal function parameters (serum creatinine and urea nitrogen) compared to the placebo group. Adverse events after FMT treatment were mild or moderate gastrointestinal symptoms. The abundance of Firmicutes and Actinobacteria decreased whereas Bacteroidetes, Proteobacteria and Roseburia spp. increased in the FMT group. CKD patients showed less disease progression after FMT administration. The administration of oral FMT in patients with CKD is a safe strategy, does not represent a risk, and has potential benefits.

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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.

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INTRODUCTION: Necrotizing Enterocolitis (NEC) is a serious intestinal disease that affects premature neonates, causing high mortality, despite the technological development in neonatal intensive care, with antibiotics, parenteral nutrition, surgery, and advanced life support. The correction of dysbiosis with fecal microbiome transplantation (FMT) has shown beneficial effects in experimental models of the disease. The different forms of administration and conservation of FMT and mixed results depending on several factors lead to questions about the mechanism of action of FMT. This study aimed to compare the effectiveness of fresh, sterile FMT and probiotic treatment under parameters of inflammation, oxidative stress, and tissue damage in a neonatal model of NEC. METHODS: One-day-old Wistar rats were used to induce NEC model. Animals were divided in five groups: Control + saline; NEC + saline; NEC + fresh FMT; NEC + sterile FMT and NEC+ probiotics. Parameters of inflammatory response and oxidative damage were measured in the gut, brain, and serum. It was also determined gut histopathological alterations. RESULTS: Proinflammatory cytokines were increased in the NEC group, and IL-10 levels decreased in the gut, brain, and serum. Fresh and sterile FMT decreased inflammation when compared to the use of probiotics. Oxidative and histological damage to the intestine was apparent in the NEC group, and both FMT treatments had a protective effect. CONCLUSION: Fresh and sterile FMT effectively reduced the inflammatory response, oxidative damage, and histological alterations in the gut and brain compared to an experimental NEC model.

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The role of gut microbiota on immune regulation and the development of autoimmune diseases such as rheumatoid arthritis (RA) is an emerging research topic. Multiple studies have demonstrated alterations on gut microbiota composition and/or function (referred to as dysbiosis) both in early and established RA patients. Still, research delineating the molecular mechanisms by which gut microorganisms induce the loss of immune tolerance or contribute to disease progression is scarce. Available data indicate that gut microbiota alterations are involved in RA autoimmune response by several mechanisms including the post-translational modification of host proteins, molecular mimicry between bacterial and host epitopes, activation of immune system and polarization toward inflammatory phenotypes, as well as induction of intestinal permeability. Therefore, in this review we analyze recent clinical and molecular evidence linking gut microbiota with the etiopathogenesis of RA. The potential of the gut microbiota as a diagnostic or severity biomarker is discussed, as well as the opportunity areas for the development of complementary therapeutic strategies based on the modulation of gut microbiota in the rheumatic patient.

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INTRODUCTION: Currently, there is a growing emphasis on the study of intestinal signaling as an influencer in the pathophysiology of neuropsychiatric diseases, and the gut-brain axis is recognized as a communication route through endocrine, immune, and neural pathways (vagus nerve). Studies have shown that diets that modify the microbiota can reduce stress-related behavior and hypothalamic-pituitary-adrenal axis activation. Investigators have used fecal microbiota transplantation (FMT) approaches to demonstrate that stress-related microbiota composition plays a causal role in behavioral changes. AIM: We hypothesized that FMT may present immunomodulatory, biochemical, endocrine, cognitive, and behavioral benefits in stress situations and that these changes can be mediated via the vagus nerve. METHODS: Animals were subjected to a chronic mild stress (CMS) protocol. In one experiment, animals were divided into five groups: control, control + FMT, control + FMT + CMS, CMS + saline, and CMS + FMT. The animals received FMT, and behavioral tests were performed; cytokine and carbonyl levels were measured. In a second experiment, animals were submitted to vagotomy and divided into two groups: CMS + FMT and CMS + vagotomy + FMT. RESULTS: Animals submitted to the CMS protocol or that received FMT from stressed animals showed behavioral changes and changes in neuroactive substances (increased IL-6 and TNF-α levels and carbonyl proteins). The FMT of healthy donors improved the analyzed parameters. In addition, vagotomy influenced beneficial FMT results, confirmed by behavioral testing and protein carbonyl in the hippocampus. CONCLUSION: Manipulation of the microbiota reversed the behavioral and biochemical changes induced by the CMS protocol, and the vagus nerve influenced the gut-brain axis response.

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During the initial stage of a study to recruit universal intestinal microbiota donors in Mexico City, we found multiple "healthy" subjects that colonized with MDRO (Multidrug-resistant organisms). We aimed to describe clinical and demographic characteristics of these individuals. This was a prospective observational study. Participants were consecutively recruited among blood donors. A fecal sample was collected from each subject and analyzed at the same day in search of MDRO through chromographic culture media and, if growth observed, later confirmed by MALDI-TOF and susceptibility testing in Vitek 2 system. From July 2018 to March 2019, 85 individuals were screened for fecal colonization. Median age was 35 years (IQR 27-46 years), and 48/85 (56.4%) were males. Seventy-two (84.7%) subjects harbored at least one MDRO. ESBL-producing microorganisms were found in 72/85 (84.3%) subjects, and E. coli was the most frequent (63/85, 74.1%). Four samples (2 E. coli, 2 P. aeruginosa, 2.4% each) harbored carbapenem-resistant Enterobacteriaceae (CRE), together with an ESBL-producing microorganism. Antibiotic use (p = 0.06) and PPIs or H2-blockers intake (p = 0.03) were more common in the colonized subjects during the previous 6-month period. We report a high incidence of enteric colonization of healthy subjects with MDRO, a condition that may be related to antibiotics or PPIs/H2-blockers consumption. This surprisingly high MDRO colonization rate in potential FMT donors emphasizes the need for careful screening of donors to avoid possible transmission to FMT recipients.

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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.

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.

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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)

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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.

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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.

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