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BACKGROUND: Immunotherapy has revolutionized the treatment of metastatic melanoma, but a significant proportion of patients still experience treatment resistance. Fecal microbiota transplantation (FMT) has emerged as a potential strategy to overcome immunotherapy resistance by modulating the gut microbiome. CASE SUMMARY: We present a case report of a 57-year-old male with metastatic melanoma refractory to immunotherapy who received FMT in combination with anti-programmed death-ligand 1 (PD-L1) immunotherapy (pembrolizumab). After failing multiple lines of treatment, the patient underwent a single FMT procedure by colonoscopy using fecal material from a female metastatic melanoma donor who successfully responded to immunotherapy. Following FMT, the patient demonstrated a response with decreased subcutaneous disease and subsequently underwent surgery to remove the residual disease. Despite a subsequent recurrence in the small bowel that was resected, the patient remained on pembrolizumab without evidence of melanoma recurrence at the time of writing. CONCLUSION: The favorable clinical and long-lasting effect we saw in our patient without significant toxicity suggests that this procedure should be considered in similar patients with immunotherapy refractory melanomas.

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BACKGROUND: Metabolic syndrome is a multifactorial disease, and the gut microbiota may play a role in its pathogenesis. Obesity, especially abdominal obesity, is associated with insulin resistance, often increasing the risk of type two diabetes mellitus, vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease. AIM: To evaluate the outcomes of fecal microbiota transplantation (FMT) in patients with metabolic syndrome. METHODS: This was a randomized, single-blind placebo-controlled trial comparing FMT and a sham procedure in patients with metabolic syndrome. We selected 32 female patients, who were divided into eight groups of four patients each. All of the patients were submitted to upper gastrointestinal endoscopy. In each group, two patients were randomly allocated to undergo FMT, and the other two patients received saline infusion. The patients were followed for one year after the procedures, during which time anthropometric, bioimpedance, and biochemical data were collected. The patients also had periodic consultations with a nutritionist and an endocrinologist. The primary end point was a change in the gut microbiota. RESULTS: There was evidence of a postprocedural change in microbiota composition in the patients who underwent FMT in relation to that observed in those who underwent the sham procedure. However, we found no difference between the two groups in terms of the clinical parameters evaluated. CONCLUSION: There were no significant differences in biochemical or anthropometric parameters, between the two groups evaluated. Nevertheless, there were significant postprocedural differences in the microbiota composition between the placebo group. To date, clinical outcomes related to FMT remain uncertain.

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La infección por Clostridioides difficile es una amenaza para la salud pública, está asociada a la atención médica, cuya complicación más frecuente es la infección recurrente, con tasas de hasta el 60% después del tercer episodio. Las opciones de tratamiento para la recurrencia de esta infección son limitadas. Una gran paradoja es tratar una infección asociada a antibióticos con más antibióticos, por ello, la piedra angular en el manejo de esta infección es la restauración de la microbiota intestinal mediante el trasplante de microbiota fecal. Objetivo. Determinar la eficacia y seguridad del trasplante de microbiota fecal para el tratamiento de la infección recurrente por Clostridioides difficile. Metodología. Se realizó una revisión bibliográfica narrativa de la literatura científica en las bases de datos PubMed y Cochrane Library empleando los Descriptores en Ciencias de la Salud (DeCS) y Medical Subject Headings (MeSH), junto con los operadores booleanos "AND/Y", "OR/O"; donde se recopilaron los estudios que cumplieron con los criterios de inclusión. Conclusión. Se concluyó que el trasplante de microbiota fecal en la infección recurrente por Clostridioides difficile es un tratamiento eficaz y seguro, con eventos adversos mínimos, aunque la seguridad a largo plazo no está bien establecida.

Clostridioides difficile infection is a public health threat, is associated with health care, the most common complication of which is recurrent infection, with rates of up to 60% after the third episode. Treatment options for recurrence of this infection are limited. A great paradox is to treat an antibiotic-associated infection with more antibiotics; therefore, the cornerstone in the management of this infection is the restoration of the intestinal microbiota by fecal microbiota transplantation. Objective. To determine the efficacy and safety of fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile infection. Methodology. A narrative bibliographic review of the scientific literature was carried out in the PubMed and Cochrane Library databases using the Health Sciences Descriptors (DeCS) and Medical Subject Headings (MeSH), together with the Boolean operators "AND/Y", "OR/O"; where the studies that met the inclusion criteria were collected. Conclusion. It was concluded that fecal microbiota transplantation in recurrent Clostridioides difficile infection is an effective and safe treatment, with minimal adverse events, although long-term safety is not well established.

A infecção por Clostridioides difficile é uma ameaça à saúde pública associada ao cuidado com a saúde, cuja complicação mais comum é a infecção recorrente, com taxas de até 60% após o terceiro episódio. As opções de tratamento para infecções recorrentes são limitadas. Um grande paradoxo é tratar uma infecção associada a antibióticos com mais antibióticos, portanto, a pedra fundamental no manejo desta infecção é a restauração da microbiota intestinal através do transplante da microbiota fecal. Objetivo. Determinar a eficácia e segurança do transplante de microbiota fecal para o tratamento de infecções recorrentes por Clostridioides difficile. Metodologia. Uma revisão bibliográfica narrativa da literatura científica foi realizada nas bases de dados da Biblioteca PubMed e Cochrane utilizando os Descritores de Ciências da Saúde (DeCS) e os Títulos de Assuntos Médicos (MeSH), juntamente com os operadores booleanos "AND/Y", "OR/O"; onde foram compilados os estudos que preenchiam os critérios de inclusão. Conclusão. Concluiu-se que o transplante de microbiota fecal em infecção recorrente por Clostridioides difficile é um tratamento eficaz e seguro com o mínimo de eventos adversos, embora a segurança a longo prazo não esteja bem estabelecida.

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Objetivo: Oferecer uma visão geral sobre os efeitos que as intervenções com o uso de probióticos, prebióticos ou Transplante de Microbiota Fecal (TMF) e suas combinações provocam nos sintomas neurocomportamentais e gastrointestinais (GI) em indivíduos com Transtorno do Espectro Autista (TEA). Metodologia: Foi realizada uma revisão integrativa (RI) da literatura nas plataformas PubMed, SciELO, LILACS e Scopus, a partir dos descritores "autistic disorder", "autism", "prebiotics", "probiotics", "fecal microbiota transplantation" e "fecal transplantation", utilizando os operadores booleanos "AND" e "OR". Foram selecionados apenas artigos dos anos de 2013 a 2022, publicados em português, inglês ou espanhol e que possuíam relação direta com o tema. Resultados: Foram analisados 24 artigos na íntegra, dos quais 14 obedeciam aos critérios de inclusão e tiveram seus resultados analisados na presente revisão. Desses, dois relataram melhora dos sintomas GI com uso de probiótico, prebiótico e/ou TMF, nove mencionaram melhora tanto dos sintomas GI como dos neurocomportamentais com as terapias utilizadas e os outros três avaliaram a mudança dos sintomas neurocomportamentais. Conclusão: As terapias com probióticos, prebióticos e TMF possuem um efeito promissor na modificação da microbiota e na melhora dos sintomas neurocomportamentais e GI em pessoas com TEA.

Objective: To provide an overview of the effects that interventions with the use of probiotics, prebiotics, or fecal microbiota transplantation and their combinations have on neurobehavioral and gastrointestinal (GI) symptoms in individuals with Autism Spectrum Disorder (ASD). Methodology: An integrative review of the literature was conducted on the PubMed, SciELO, LILACS, and Scopus platforms using the descriptors "autistic disorder", "autism", "prebiotics", "probiotics", "fecal microbiota transplantation", and "fecal transplantation", using the Boolean operators "AND" and "OR". Only articles published between 2013 and 2022 in Portuguese, English, or Spanish and directly related to the topic were selected. Results: Twenty-four articles were fully analyzed, of which fourteen met the inclusion criteria and had their results analyzed in this review. Of these, two reported improvement in GI symptoms with the use of probiotics, prebiotics, and/or fecal microbiota transplantation, nine mentioned improvement in both GI and neurobehavioral symptoms with the therapies used, and the other three evaluated the change in neurobehavioral symptoms. Conclusion: Probiotic, prebiotic, and fecal microbiota transplantation therapies have a promising effect on modifying the microbiota and improving neurobehavioral and GI symptoms in individuals with ASD.

Objetivo: Proporcionar una visión general de los efectos que las intervenciones con el uso de probióticos, prebióticos o trasplante de microbiota fecal y sus combinaciones tienen sobre los síntomas neuroconductuales y gastrointestinales (GI) en individuos con Trastorno del Espectro Autista (TEA). Metodología: Se realizó una revisión integradora de la literatura en las plataformas PubMed, SciELO, LILACS y Scopus utilizando los descriptores "autistic disorder", "autism", "prebiotics", "probiotics", "fecal microbiota transplantation" y "fecal transplantation", utilizando los operadores booleanos "AND" y "OR". Solo se seleccionaron artículos publicados entre 2013 y 2022 en portugués, inglés o español y directamente relacionados con el tema. Resultados: Veinticuatro artículos fueron analizados en su totalidad, de los cuales catorce cumplieron los criterios de inclusión y sus resultados fueron analizados en esta revisión. De estos, dos reportaron mejoría en los síntomas GI con el uso de probióticos, prebióticos y/o trasplante de microbiota fecal, nueve mencionaron mejoría tanto en los síntomas GI como neuroconductuales con las terapias utilizadas, y los otros tres evaluaron el cambio en los síntomas neuroconductuales. Conclusiones: Las terapias con probióticos, prebióticos y trasplante de microbiota fecal tienen un efecto prometedor en la modificación de la microbiota y la mejora de los síntomas neuroconductuales y GI en individuos con TEA. PALABRAS CLAVE: Autismo; Microbiota; Prebióticos; Probióticos; Trasplante de Microbiota Fecal.

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ABSTRACT Introduction: despite being extremely effective in some cases, up to 70% of patients with melanoma do not respond to anti-PD-1/PD-L1 (primary resistance) and many of the responders eventually progress (secondary resistance). Extensive efforts are being made to overcome this resistance through new strategies, especially aimed at modulating the intestinal microbiota. Objective: to assess whether fecal microbiota transplantation (FMT), associated with immunotherapy, is beneficial in the clinical course of patients with refractory melanoma. Methods: this is a scope review, based on studies collected on the MEDLINE, ScienceDirect, The Cochrane Library, Embase and BMJ Journals; using the terms: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; and "Microbiota". Clinical trials, in English, with relevant data on the subject and fully available were included. A cut-off period was not determined, due to the limited amount of evidence on the topic. Results: crossing the descriptors allowed the identification of 342 publications and, after applying the eligibility criteria, allowed the selection of 4 studies. From the analyses, it was observed that a considerable part of those studied overcame resistance to immune checkpoint inhibitors after FMT, with better response to treatment, less tumor growth and increased beneficial immune response. Conclusion: it is noted that FMT favors the response of melanoma to immunotherapy, translated into significant clinical benefit. However, further studies are necessary for the complete elucidation of the bacteria and the mechanisms involved, as well as for the translation of new evidence to oncological care practice.

RESUMO Introdução: apesar de extremamente eficaz em alguns casos, até 70% dos pacientes com melanoma não respondem aos anti-PD-1/PD-L1 (resistência primária) e muitos dos respondedores, eventualmente, acabam progredindo (resistência secundária). Extensos esforços estão sendo realizados para superar esta resistência através de novas estratégias, sobretudo, visando a modulação da microbiota intestinal. Objetivo: avaliar se o transplante de microbiota fecal (TMF), associado à imunoterapia, é benéfico no curso clínico do paciente com melanoma refratário. Métodos: trata-se de uma revisão de escopo, baseada em estudos coletados nas plataformas MEDLINE, ScienceDirect, The Cochrane Library, Embase e BMJ Journals; utilizando os descritores: "Antibodies, Monoclonal"; "Drug Resistance, Neoplasm"; "Fecal Microbiota Transplantation"; "Host Microbial Interactions"; "Immunotherapy"; "Melanoma"; e "Microbiota". Foram incluídos ensaios clínicos, na língua inglesa, com dados relevantes sobre a temática e disponíveis integralmente. Não foi determinado um período de corte temporal, devido à quantidade limitada de evidências sobre o tema. Resultados: o cruzamento dos descritores permitiu a identificação de 342 publicações e, após a aplicação dos critérios de elegibilidade, permitiu a seleção de 4 estudos. A partir das análises, observou-se que grande parte dos estudados superaram a resistência aos inibidores do checkpoint imunológico pós-TMF, com melhor resposta ao tratamento, menor crescimento tumoral e aumento da resposta imunológica benéfica. Conclusão: nota-se que o TMF favorece a resposta do melanoma à imunoterapia, traduzido por benefício clínico significativo. Entretanto, novos estudos são necessários para a completa elucidação das bactérias e mecanismos envolvidos, bem como para que haja a translação das novas evidências para a prática assistencial oncológica.

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Abstract Introduction The relationship between humidity and systemic lupus erythematosus (SLE) has yielded inconsistent results in prior research, while the effects of humidity on lupus in animal experiments and its underlying mechanism remain inadequately explored. Methods The present study aimed to investigate the impact of high humidity (80 ± 5%) on lupus using female and male MRL/lpr mice, with a particular focus on elucidating the role of gut microbiota in this process. To this end, fecal microbiota transplantation (FMT) was employed to transfer the gut microbiota of MRL/lpr mice under high humidity to blank MRL/lpr mice under normal humidity (50 ± 5%), allowing for an assessment of the effect of FMT on lupus. Results The study revealed that high humidity exacerbated lupus indices (serum anti-dsDNA, ANA, IL-6, and IFN- g, and renal pathology) in female MRL/lpr mice but had no significant effect on male MRL/lpr mice. The aggravation of lupus caused by high humidity may be attributed to the increased abundances of the Rikenella, Romboutsia, Turicibacter, and Escherichia-Shigella genera in female MRL/lpr mice. Furthermore, FMT also exacerbated lupus in female MRL/lpr mice but not in male MRL/lpr mice. Conclusion In summary, this study has demonstrated that high humidity exacerbated lupus by modulating gut microbiota in female MRL/lpr mice. The findings underscore the importance of considering environmental factors and gut microbiota in the development and progression of lupus, particularly among female patients.

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El diagnóstico de la infección por Clostridioides dfficile (ICD) ha aumentado en el embarazo y periparto. Cambios fisiológicos e inmunológicos normales durante el embarazo pueden incrementar el riesgo de ICD. Mujeres embarazadas con ICD tienen una mayor frecuencia de fracaso al tratamiento y una significativa morbilidad y mortalidad. El trasplante de microbiota fecal (TMF) se ha convertido en el tratamiento estándar de la ICD recurrente y refractaria. Sin embargo, existen escasos datos sobre sus resultados en mujeres embarazadas. Presentamos el caso de una mujer embarazada que se sometió con éxito a un TMF para el tratamiento de una ICD recurrente.

The diagnosis of Clostridioides dfficile infection (CDI) in pregnant and peripartum women has increased. In this scenario, there are higher rates of treatment failure and a significant maternal morbidity and mortality. Fecal microbiota transplant (FMT) has become the gold standard for the treatment of recurrent and refractory CDI however, there are few data on its results in pregnant patients. This case showed that FMT could be a therapeutic strategy in pregnant women with recurrent CDI.

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Clostridioides difficile infection (CDI) is a major public health problem and responsible for significant morbidity and mortality. Eighty percent of CDIs occur in adults older than 65 years of age due to a decreased gastrointestinal microbial diversity, immunosenescence and frailty. Thus, the most reported risk factor for recurrent CDI is older age since nearly 60% of cases occur in individuals aged ≥ 65 years. Fecal microbiota transplantation (FMT) is a highly cost-effective alternative to antibiotic treatment for patients with recurrent CDI. We report a 75-year-old male with recurrent CDI, who received a FMT after several unsuccessful antimicrobial treatments. He had a satisfactory evolution after the procedure and remained without diarrhea during the ensuing five months.

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Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.

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BACKGROUND: Clostridiodes difficile infection (CDI) is one of the most common causes of antibiotic-associated diarrhea in children. Conventional antibiotics and emerging fecal microbiota transplantation (FMT) are used to treat CDI. METHODS: Children with CDI admitted to the Shanghai Children's Hospital, from September 2014 to September 2020, were retrospectively included to this observational study. Pediatric patients were assigned as initial CDI and recurrent CDI (RCDI), and symptoms, comorbidities, imaging findings, laboratory tests, and treatments were systematically recorded and analyzed. RESULTS: Of 109 pediatric patients with CDI, 58 were boys (53.2%), and the median age was 5 years (range, 2-9 years). The main clinical symptoms of CDI children were diarrhea (109/109, 100%), hematochezia (55/109, 50.46%), abdominal pain (40/109, 36.70%); fever, pseudomembrane, vomit, and bloating were observed in 39 (35.78%), 33 (30.28%), and 24 (22.02%) patients, respectively. For the primary therapy with conventional antibiotics, 68 patients received metronidazole, and 41 patients received vancomycin. RCDI occurred in 48.53% (33/68) of those initially treated with metronidazole compared with 46.33% (19/41) of those initially treated with vancomycin (p=0.825). The total resolution rate of FMT for RCDI children was significantly higher than with vancomycin treatment (28/29, 96.55% vs 11/23, 47.83%, p < 0.001). There were no serious adverse events (SAEs) reported after two months of FMT. CONCLUSIONS: The major manifestations of children with CDI were diarrhea, hematochezia, and abdominal pain. The cure rate of FMT for pediatric RCDI is superior to vancomycin treatment.

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The aim of this scoping review was to determine the characteristics of studies evaluating fecal microbiota transplantation (FMT), as well as its effects and safety as a therapeutic intervention for people living with human immunodeficiency virus (HIV). We conducted a scoping review following the methodology of the Joanna Briggs Institute. We searched the following databases: PubMed, Web of Science, Scopus, Embase, Cochrane Library, and Medline until September 19, 2021. Studies that used FMT in people living with HIV and explored its effects on the health of these people were included. Two randomized and 2 uncontrolled clinical trials with a total of 55 participants were included. Participants were well-controlled HIV-infected people. Regarding microbiota changes, three studies found significant post-FMT increases in Fusobacterium, Prevotella, α-diversity, Chao index, and/or Shannon index, and/or decreases in Bacteroides. Regarding markers of intestinal damage, one study found a decrease in intestinal fatty acid binding protein post-FMT, and another study found an increase in zonulin. Other outcomes evaluated by the studies were as follows: markers of immune and inflammatory activation, markers of immunocompetence (CD4+, and CD8+ T lymphocytes), and HIV viral load; however, none showed significant changes. Clinical outcomes were not evaluated by these studies. Regarding the safety of FMT, only mild adverse events were appreciated. No serious adverse event was reported. The clinical evidence for FMT in people living with HIV is sparse. FMT appears to have good tolerability and, no serious adverse event has been reported so far. Further clinical trials and evaluation of clinically important biomedical outcomes for FMT in people living with HIV are needed.

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The prevalence of Carbapenem-resistant Enterobacteriaceae (CRE) has increased dramatically in recent years and has become a global public health issue. Since carbapenems are considered the last drugs of choice, infections caused by these pathogens are difficult to treat and carry a high risk of mortality. Several antibiotic combination regimens have been utilized for the management of CRE infections or to eradicate colonization in CRE carriers with variable clinical responses. In addition, recent studies have explored the use of fecal microbiota transplantation (FMT) to eradicate CRE infections. Here, we conducted a systematic review of publications in which FMT was used to eliminate CRE colonization in infected individuals. We searched the PubMed, Cochrane, and Medline databases up to November 30, 2021. Ten studies (209 patients) met the inclusion criteria for this review with three articles describing retrospective cohorts (n = 53 patients) and seven reporting prospective data (n = 156 patients), including one randomized open-label clinical trial. All studies were published between 2017 and 2021 with eight studies from Europe and two from South Korea. There were substantial variations in terms of outcome measurements and study endpoint among these studies. Among the 112 FMT recipients with confirmed CRE colonization, CRE decolonization was reported in 55/90 cases at one month after FMT and at the end of the study follow-up (6-12 months), decolonization was documented in 74/94 (78.7%) patients. The predominant CRE strains reported were Klebsiella pneumoniae and Escherichia coli and the most frequently documented carbapenemases were KPC, OXA-48, and NDM. In general, FMT was well tolerated, with no severe complications reported even in immunosuppressed patients and in those with multiple underlying conditions. In conclusion, FMT appears to be safe and effective in eradicating CRE colonization, however, more studies, especially randomized trials, are needed to validate the safety and clinical utility of FMT for CRE eradication.

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La sepsis es la respuesta desordenada del organismo a la infección y se caracteriza por un daño a los órganos que puede ser irreversible y mortal. El microbioma intestinal regula a un grupo de mecanismos homeostáticos en el huésped, como la función inmunológica y la protección de la barrera intestinal, la pérdida de la estructura y la función microbiana intestinal normal; además, se ha asociado con el inicio de enfermedades de características diversas. La evidencia reciente ha demostrado un nexo entre el microbioma intestinal y la sepsis: la alteración del microbioma intestinal aumenta la susceptibilidad a la sepsis a través de varios mecanismos como la expansión de bacterias intestinales patógenas, la respuesta proinflamatoria marcada y la disminución de la formación de productos microbianos beneficiosos como los ácidos grasos de cadena corta. Una vez establecida la sepsis, la alteración del microbioma intestinal empeora y aumenta la susceptibilidad a la disfunción del órgano terminal. Existen pruebas limitadas de que las terapias basadas en microbiomas (que incluyen a probióticos y a la descontaminación digestiva selectiva) pueden disminuir el riesgo de sepsis y mejorar sus resultados en poblaciones de pacientes seleccionadas, pero las preocupaciones sobre la seguridad causan una aceptación limitada. Si bien gran parte de la evidencia que vincula el microbioma intestinal y la sepsis se ha establecido en estudios preclínicos, aún es necesaria la evidencia clínica en distintas áreas.

Sepsis is the body's overwhelming response to an infection. It is characterized by damage to the organs that may be irreversible and life-threatening. The gastrointestinal microbiome regulates a series of homeostatic mechanisms in the host, such as the immune function and the protection of the intestinal barrier, and the loss of normal intestinal microbial structure and function. Moreover, it has been associated with the onset of diseases of diverse characteristics. Recent evidence has shown a link between the gastrointestinal microbiome and sepsis: the alteration of the gastrointestinal microbiome increases the susceptibility to sepsis through various mechanisms, including the expansion of pathogenic intestinal bacteria, marked pro-inflammatory response and decreased production of beneficial microbial products such as short-chain fatty acids. Once sepsis is established, the alteration of the gastrointestinal microbiome worsens and the susceptibility to end-organ dysfunction increases. There is limited evidence that microbiome-based therapies, which include probiotics and selective digestive decontamination, can decrease the risk of sepsis and improve its outcomes in selected patient populations. However, safety concerns generate limited acceptance. While much of the evidence linking the gastrointestinal microbiome and sepsis has been established in preclinical studies, clinical evidence is still necessary in many areas.

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ABSTRACT Background: Clostridiodes difficile infection (CDI) is one of the most common causes of antibiotic-associated diarrhea in children. Conventional antibiotics and emerging fecal micro-biota transplantation (FMT) are used to treat CDI. Methods: Children with CDI admitted to the Shanghai Children's Hospital, from September 2014 to September 2020, were retrospectively included to this observational study. Pediatric patients were assigned as initial CDI and recurrent CDI (RCDI), and symptoms, comorbid-ities, imaging findings, laboratory tests, and treatments were systematically recorded and analyzed. Results: Of 109 pediatric patients with CDI, 58 were boys (53.2%), and the median age was 5 years (range, 2-9 years). The main clinical symptoms of CDI children were diarrhea (109/109, 100%), hematochezia (55/109, 50.46%), abdominal pain (40/109, 36.70%); fever, pseudomembrane, vomit, and bloating were observed in 39 (35.78%), 33 (30.28%), and 24 (22.02%) patients, respectively. For the primary therapy with conventional antibiotics, 68 patients received metronidazole, and 41 patients received vancomycin. RCDI occurred in 48.53% (33/68) of those initially treated with metronidazole compared with 46.33% (19/41) of those initially treated with vancomycin (p=0.825). The total resolution rate of FMT for RCDI children was significantly higher than with vancomycin treatment (28/29, 96.55% vs 11/23, 47.83%, p < 0.001). There were no serious adverse events (SAEs) reported after two months of FMT. Conclusions: The major manifestations of children with CDI were diarrhea, hematochezia, and abdominal pain. The cure rate of FMT for pediatric RCDI is superior to vancomycin treatment.

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Background: The treatment of Clostridioides difficile is based on an antibiotics cycle, but for individuals who have more than two recurrences, fecal microbiota transplantation can be considered as a therapeutic option. Objective: To describe the technique and results of fecal microbiota transplantation performed for recurrent infection by Clostridioides difficile. Methods: Retrospective, cross-sectional study based on a review of medical records of patients undergoing transplantation of fecal microbiota. Data were obtained on the criteria used to select the donor, the preparation of stools in the laboratory and the method of delivery of the material offered, as well as information regarding the characteristics of the recipient, such as: gender, age, comorbidities, hospitalizations, use of antibiotics prior to infection, clinical presentation, diagnosis and treatments performed for Clostridioides difficile. After transplantation, data on efficacy, outcome, follow-up time and procedure complications were considered. Results: Between 2012 and 2019, 11 patients underwent fecal microbiota transplantation. The use of antibiotics prior to infection occurred in 9 patients, no patient was hospitalized in the previous 6 months due to another etiology. All had at least 2 cycles of vancomycin for recurrent disease. Of the total of 11 patients, 2 required 2 infusions and 1 patient required 3, totaling 15 fecal microbiota transplants. The success rate was 81.8% with only one infusion and 90.9% resolution considering patients who needed more than one infusion. Conclusion: Fecal microbiota transplantation is a feasible therapy with resolution in 90.9% of cases as a treatment for recurrent Clostridioides difficile infection.

Contexto: O tratamento do Clostridioides difficile é baseado em ciclo antimicrobiano, mas para os indivíduos que apresentam mais de duas recorrências, pode-se considerar o transplante de microbiota fecal como opção terapêutica. Objetivo: Descrever a técnica e os resultados do transplante de microbiota fecal realizados para infecção recorrente por Clostridioides difficile. Métodos: Estudo retrospectivo, transversal, baseado em revisão de prontuários de pacientes submetidos ao transplante de microbiota fecal. Foram obtidos dados sobre os critérios empregados para seleção do doador, o preparo das fezes e o método de entrega do material, além de informações referentes às características do receptor, como: sexo, idade, comorbidades, internamentos, uso de antimicrobiano prévio à infecção, apresentação clínica, diagnóstico e tratamentos realizados para o Clostridioides difficile. Após o transplante, dados sobre eficácia, desfecho, tempo de seguimento e complicações do procedimento foram considerados. Resultados: Entre 2012 e 2019, 11 pacientes foram submetidos ao transplante de microbiota fecal. O uso de antimicrobiano prévio à infecção ocorreu em 9 pacientes, nenhum paciente internou nos 6 meses anteriores por outra etiologia. Todos fizeram pelo menos 2 ciclos de vancomicina para doença recorrente. Do total de 11 pacientes, 2 necessitaram de 2 infusões e 1 paciente necessitou de 3, totalizando 15 transplantes de microbiota fecal. O sucesso foi de 81,8% com apenas uma infusão e resolução de 90,9% considerando pacientes que necessitaram de mais de uma infusão. Conclusão: O transplante de microbiota fecal é uma terapia factível e com resolução em 90,9% dos casos como tratamento de infecção recorrente por Clostridioides difficile.

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Resumen La infección por Clostridioides difficile (iCD) es la causa más frecuente de diarrea nosocomial. La primera línea terapéutica es la vancomicina asociada o no al metronidazol. En los últimos años se incrementó el número de fracasos terapéuticos con una mayor frecuencia de formas refractarias o recurrentes. El trasplante de microbiota fecal (TMF) ha surgido como una opción terapéutica para estos casos. Se evaluó la seguridad y la tasa de resolución empleando el TMF en un estudio observacional abierto y prospectivo de 21 pacientes con iCD recurrentes o refractarias internados entre los años 2016 y 2019. La edad media fue de 76.5 años (33-92). Diez presentaron una forma recurrente y 11 una refractaria, 18 fueron graves y 3 fulminantes. En 20 casos el TMF se administró por la vía digestiva alta y en uno por presentar íleo se utilizó la vía baja. Se empleó TMF de heces frescas en un caso y el resto recibió muestras congeladas de un banco de microbiota. Veinte pacientes (95.2%) tuvieron respuesta terapéutica favorable sin presentar recurrencias. Un caso recurrente, con osteomielitis y falla multiorgánica, no tuvo resolución tras dos TMF. La respuesta fue similar en las formas recurrentes y refractarias. Siete pacientes (31%) tuvieron efectos adversos leves y autolimitados. El TMF ha demostrado una alta eficacia como tratamiento de rescate de las formas graves de iCD, con escasos y leves efectos adversos. Contar con un banco de microbiota fecal resulta fundamental para disponer de este recurso terapéutico oportunamente.

Abstract Clostridiodes difficile infection (CDi) is the most common cause of nosocomial diarrhea. Vancomycin, associated or not to metronidazol, is the treatment of choice. However, the rate of treatment failure has increased over the last years and fecal microbiota transplantation (FMT) has emerged as a therapeutic option. To evaluate safety and efficacy of FMT were enrolled 21 hospitalized patients with refractory or recurrent CDi between 2016 and 2019. Fourteen (66%) patients were men and the average age was 76.5 years (range 33-92). Ten had recurrent and 11 refractory CDi, and 18 presented severe and 3 fulminant clinical forms. In 20 cases the FMT was delivered through a nasojejunal tube and in one patient with ileo via enema infusion. Frozen fecal from a stool bank were administered in 20 and in the remaining was used fresh fecal matter. The rate of resolution was observed in 20 patients (95.2%) and none presented recurrence. The response rate was similar in recurrent or refractory forms (9/10 vs 11/11 respectively). One patient with osteomyelitis and multiple organ failure received 2 FMT without response and died. Seven patients (31%) presented mild and self-limited adverse effects. FMT has shown a high efficacy as rescue treatment in cases with refractory or recurrent CDi regardless of severity, with mild side effects. Availability of a stool banks provide reliable, timely and equitable access to FMT for CDi.

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ABSTRACT BACKGROUND: Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC). OBJECTIVE: The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection. METHODS: The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects. RESULTS: A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%. CONCLUSION: The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.

RESUMO CONTEXTO: O Transplante de microbiota fecal (TMF) é uma importante opção terapêutica para a infecção recorrente ou refratária pelo Clostridioides difficile, sendo método seguro e eficaz. Resultados iniciais sugerem que o TMF também desempenha papel relevante em outras afecções cuja patogênese envolve a alteração da microbiota intestinal. No entanto, seu uso sistematizado é pouco difundido, especialmente no Brasil. Na última década, surgiram múltiplos relatos e séries de casos utilizando diferentes protocolos para o TMF, sem padronização de métodos e com taxas de resposta variáveis. No Brasil, poucos casos isolados de TMF foram relatados sem a implantação de um Centro de Transplante de Microbiota Fecal (CTMF). OBJETIVO: O principal objetivo deste estudo foi descrever o processo de implantação de um CTMF com banco de fezes, em hospital universitário brasileiro, para tratamento de infecção recorrente e refratária pelo C. difficile. MÉTODOS: O CTMF foi estruturado dentro dos critérios exigidos e aprovados por organismos internacionais como o Food and Drug Administration, Grupo Europeu de Transplante de Microbiota Fecal e em consonância com os aspectos epidemiológicos e regulatórios nacionais. RESULTADOS: Foi estabelecida toda uma plataforma envolvida na estruturação de um centro de transplante com fezes congeladas. Determinou-se os critérios para seleção de doadores, processamento e armazenamento de amostras, manejo dos receptores antes e após o procedimento, uniformização de vias de administração do substrato fecal e seguimento a curto e longo prazo dos pacientes transplantados. A seleção dos doadores foi conduzida em três etapas: pré-triagem, avaliação clínica e exames laboratoriais. Boa parte dos candidatos foram excluídos na primeira (75,4%) e segunda etapa (72,7%). Os principais critérios clínicos de exclusão foram: diarreia aguda recente, excesso de peso (IMC ≥25 kg/m2) e distúrbios gastrointestinais crônicos. Quatro dos 134 candidatos foram selecionados após a triagem completa, com taxa de detecção de doadores de 3%. CONCLUSÃO: A implantação de um CTMF, inédito no nosso meio, possibilita o acesso de pacientes com infecção recorrente e refratária pelo C. difficile a tratamento inovador, seguro, com elevada taxa de sucesso e pouco disponível no Brasil. A seleção apropriada de doadores qualificados é vital no processo de implantação de um CTMF. A avaliação clínica rigorosa dos doadores permitiu o uso racional de recursos para realização de exames laboratoriais. Um CTMF possibilita tratamento sob demanda, em maior escala, menos personalizados, com mais segurança e rastreabilidade. Este protocolo fornece subsídios para a realização de TMF em países emergentes.

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Clostridiodes difficile infection (CDi) is the most common cause of nosocomial diarrhea. Vancomycin, associated or not to metronidazol, is the treatment of choice. However, the rate of treatment failure has increased over the last years and fecal microbiota transplantation (FMT) has emerged as a therapeutic option. To evaluate safety and efficacy of FMT were enrolled 21 hospitalized patients with refractory or recurrent CDi between 2016 and 2019. Fourteen (66%) patients were men and the average age was 76.5 years (range 33-92). Ten had recurrent and 11 refractory CDi, and 18 presented severe and 3 fulminant clinical forms. In 20 cases the FMT was delivered through a nasojejunal tube and in one patient with ileo via enema infusion. Frozen fecal from a stool bank were administered in 20 and in the remaining was used fresh fecal matter. The rate of resolution was observed in 20 patients (95.2%) and none presented recurrence. The response rate was similar in recurrent or refractory forms (9/10 vs 11/11 respectively). One patient with osteomyelitis and multiple organ failure received 2 FMT without response and died. Seven patients (31%) presented mild and self-limited adverse effects. FMT has shown a high efficacy as rescue treatment in cases with refractory or recurrent CDi regardless of severity, with mild side effects. Availability of a stool banks provide reliable, timely and equitable access to FMT for CDi.

La infección por Clostridioides difficile (iCD) es la causa más frecuente de diarrea nosocomial. La primera línea terapéutica es la vancomicina asociada o no al metronidazol. En los últimos años se incrementó el número de fracasos terapéuticos con una mayor frecuencia de formas refractarias o recurrentes. El trasplante de microbiota fecal (TMF) ha surgido como una opción terapéutica para estos casos. Se evaluó la seguridad y la tasa de resolución empleando el TMF en un estudio observacional abierto y prospectivo de 21 pacientes con iCD recurrentes o refractarias internados entre los años 2016 y 2019. La edad media fue de 76.5 años (33-92). Diez presentaron una forma recurrente y 11 una refractaria, 18 fueron graves y 3 fulminantes. En 20 casos el TMF se administró por la vía digestiva alta y en uno por presentar íleo se utilizó la vía baja. Se empleó TMF de heces frescas en un caso y el resto recibió muestras congeladas de un banco de microbiota. Veinte pacientes (95.2%) tuvieron respuesta terapéutica favorable sin presentar recurrencias. Un caso recurrente, con osteomielitis y falla multiorgánica, no tuvo resolución tras dos TMF. La respuesta fue similar en las formas recurrentes y refractarias. Siete pacientes (31%) tuvieron efectos adversos leves y autolimitados. El TMF ha demostrado una alta eficacia como tratamiento de rescate de las formas graves de iCD, con escasos y leves efectos adversos. Contar con un banco de microbiota fecal resulta fundamental para disponer de este recurso terapéutico oportunamente.

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OBJECTIVE: The aim of this study was to investigate the protective effects of probiotics and fecal transplantation on inflammatory and oxidative parameters in the intestines of two rat models of sepsis. METHODS: Rats were treated with prebiotics, probiotics, or symbiotics and exposed to lipopolysaccharide (LPS) or zymosan after 15 d to induce endotoxemia. Oxidative damage and inflammation were analyzed, and histologic examination of the intestinal tissue was performed. Fecal microbiota transplantation (FMT) was carried out in LPS- and zymosan-induced rat models of sepsis. RESULTS: Supplementation with symbiotics for 15 d effectively reduced the inflammatory parameters compared with supplementation for 7 d. Probiotics, prebiotics, and symbiotics exerted different effects on the evaluated parameters. In general, Lactobacillus rhamnosus and L. casei exerted better local protective effects. Evaluation of the role of the intestinal microbiota through FMT revealed its protective effects irrespective of the previous treatment with probiotics. CONCLUSION: Probiotic strains significantly differ among themselves and exert different effects on the host's health. Symbiotics and FMT could offer additional immunomodulatory benefits to drug therapy, thus serving as a new therapeutic alternative in pediatric patients with sepsis.

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Introdução: O Transplante de Microbiota Fecal (TMF) é uma importante opção terapêutica para a infecção recorrente ou refratária pelo Clostridioides difficile, sendo método seguro e eficaz. Resultados iniciais sugerem que o TMF também desempenha um papel relevante em outras afecções cuja patogênese envolve a alteração da microbiota intestinal. No entanto, seu uso sistematizado é pouco difundido, especialmente no Brasil. Na última década, surgiram múltiplos relatos e séries de casos utilizando diferentes protocolos para o TMF, sem padronização de métodos e com taxas de resposta variáveis. No Brasil, foram relatados poucos casos isolados de TMF, com taxa de sucesso em torno de 90%, realizados de forma experimental, sem a implantação de um Centro de Transplante de Microbiota Fecal (CTMF). É objetivo principal desse estudo descrever o processo envolvido na implantação de um Centro de Transplante de Microbiota Fecal (CTMF) no Instituto Alfa de Gastroenterologia do Hospital das Clínicas da UFMG/EBSERH (IAG-HC/UFMG) para o tratamento de infecção recorrente e refratária pelo C. difficile e analisar prospectivamente os resultados do tratamento a curto e longo prazo. Métodos: O CTMF foi estruturado dentro dos critérios exigidos e aprovados por organismos internacionais como o FDA (Food and Drug Administration), Grupo Europeu de Transplante de Microbiota Fecal e em consonância com os aspectos epidemiológicos e regulatórios nacionais. Resultados: Foi estabelecida plataforma que define todas as etapas envolvidas na seleção de doadores universais, processamento e armazenamento de amostras, uniformização de vias de administração do substrato fecal e seguimento a curto e longo prazo dos pacientes transplantados. A seleção de doadores foi realizada em três etapas: pré-triagem, avaliação clínica e triagem laboratorial. A maioria dos candidatos foi excluída na primeira (75,4%) e segunda etapa (72,7%). Os principais critérios clínicos de exclusão foram: diarreia aguda recente, excesso de peso (índice de massa corporal ≥ 25 kg / m²) e distúrbios gastrointestinais crônicos. Apenas quatro dos 134 candidatos foram selecionados como doadores após rastreio completo, com taxa de detecção de doadores habilitados de 3%. Ao todo foram realizados 11 transplantes em 10 pacientes com ICD recorrente. A taxa de resolução primária, com apenas um procedimento, foi de 80% e a taxa de remissão geral, após segundo TFM, foi de 90%. A ocorrência de eventos adversos foi semelhante à observada em outros estudos. A maioria dos eventos adversos foram autolimitados e de resolução espontânea. Conclusão: A implantação de um centro de transplante, inédito no nosso país, permitiu o acesso de pacientes com infecção recorrente pelo C. difficile a tratamento inovador, seguro e efetivo. A seleção adequada de doadores qualificados é vital no processo de implantação de um CTMF. A rigorosa avaliação clínica dos doadores permitiu o uso racional de recursos. Um centro de transplante de microbiota possibilita oferecer um tratamento sob demanda, menos personalizado, com mais segurança e rastreabilidade. Mesmo em países emergentes, onde há preocupação com doenças tropicais e infecciosas, o TMF parece ser uma estratégia segura e efetiva no tratamento de ICD recorrente.

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