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1.
EBioMedicine ; 69: 103443, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34186487

RESUMO

BACKGROUND: Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257). METHODS: Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3 ml solution of either maternal vaginal microbes (CS-seeded, n = 12) or sterile water (CS-placebo, n = 13). Vaginally-born neonates were used as the reference control (VB, n = 22). Clinical assessments occurred within the first 2 h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events. FINDINGS: Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment. INTERPRETATION: Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome. FUNDING: Health Research Council of New Zealand, A Better Start - National Science Challenge.


Assuntos
Cesárea/efeitos adversos , Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal , Doenças do Recém-Nascido/microbiologia , Vagina/microbiologia , Administração Oral , Adulto , Bacteroides/patogenicidade , Transplante de Microbiota Fecal/efeitos adversos , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/etiologia , Doenças do Recém-Nascido/prevenção & controle , Masculino
2.
World J Gastroenterol ; 27(22): 2921-2943, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34168399

RESUMO

Irritable bowel syndrome (IBS) affects about 12% of the global population. Although IBS does not develop into a serious disease or increase mortality, it results in a considerable reduction in the quality of life. The etiology of IBS is not known, but the intestinal microbiota appears to play a pivotal role in its pathophysiology. There is no effective treatment for IBS, and so the applied treatments clinically focus on symptom relief. Fecal microbiota transplantation (FMT), an old Chinese treatment, has been applied to IBS patients in seven randomized controlled trials (RCTs). Positive effects on IBS symptoms in various degrees were obtained in four of these RCTs, while there was no effect in the remaining three. Across the seven RCTs there were marked differences in the selection processes for the donor and treated patients, the transplant dose, the route of administration, and the methods used to measure how the patients responded to FMT. The present frontier discusses these differences and proposes: (1) criteria for selecting an effective donor (superdonor); (2) selection criteria for patients that are suitable for FMT; (3) the optimal FMT dose; and (4) the route of transplant administration. FMT appears to be safe, with only mild, self-limiting side effects of abdominal pain, cramping, tenderness, diarrhea, and constipation. Although it is early to speculate about the mechanisms underlying the effects of FMT, the available data suggest that changes in the intestinal bacteria accompanied by changes in fermentation patterns and fermentation products (specifically short-chain fatty acids) play an important role in improving the IBS symptoms seen after FMT. FMT appears to be a promising treatment for IBS, but further studies are needed before it can be applied in everyday clinical practice.


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Diarreia , Ácidos Graxos Voláteis , Transplante de Microbiota Fecal/efeitos adversos , Fezes , Humanos , Síndrome do Intestino Irritável/terapia
3.
Mayo Clin Proc ; 96(6): 1418-1425, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34088413

RESUMO

OBJECTIVE: To report experience with fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) and provide recommendations for management of rCDI and donor testing during the COVID-19 pandemic. METHODS: A retrospective study of patients with rCDI who underwent FMT from May 26, 2020, to September 30, 2020, with stool from well-screened donors with health and infectious screening and a newly implemented strategy for COVID-19 screening with every 2-week bookend testing with stool quarantine. Patients were followed up for development of rCDI and COVID-19. RESULTS: Of the 57 patients who underwent FMT for rCDI, 29 were tested for COVID-19 via nasopharyngeal polymerase chain reaction (PCR) and 22 via serology. All results were negative, except for 1 positive serology. Donor testing every 2 weeks for COVID-19 via serology and nasopharyngeal swab PCR was negative, except for 2 donors at 1 center who were excluded. Three patients had rCDI after FMT, and 1 underwent repeat FMT. One patient developed respiratory symptoms suggestive of COVID-19 and tested negative via nasopharyngeal PCR. Eleven patients who underwent COVID-19 testing for elective procedures or hospitalizations tested negative. No SARS-CoV-2 transmission was noted. CONCLUSIONS: With appropriate donor screening, FMT can be performed safely for rCDI during the COVID-19 pandemic. Development of a validated stool assay for SARS-CoV-2 will simplify this process further.


Assuntos
COVID-19/epidemiologia , Clostridioides difficile , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/prevenção & controle , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
4.
World J Gastroenterol ; 27(18): 2219-2237, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34025075

RESUMO

BACKGROUND: Faecal microbiota transplantation (FMT) seems to be a promising treatment for irritable bowel syndrome (IBS) patients. In Western countries (United States and Europe), there is a female predominance in IBS. A sex difference in the response to FMT has been reported recently in IBS patients. AIM: To investigate whether there was a sex difference in the response to FMT in the IBS patients who were included in our previous randomized controlled trial of the efficacy of FMT. METHODS: The study included 164 IBS patients who participated in our previous randomized controlled trial. These patients had moderate-to-severe IBS symptoms belonging to the IBS-D (diarrhoea-predominant), IBS-C (constipation-predominant) and IBS-M (mixed) subtypes, and had not responded to the National Institute for Health and Care Excellence (NICE)-modified diet. They belonged in three groups: placebo (own faeces), and active treated group (30-g or 60-g superdonor faeces). The patients completed the IBS severity scoring system (IBS-SSS), Fatigue Assessment Scale (FAS) and the IBS quality of life scale (IBS-QoL) questionnaires at the baseline and 2 wk, 1 mo and 3 mo after FMT. They also provided faecal samples at the baseline and 1 mo after FMT. The faecal bacteria profile and dysbiosis were determined using the 16S rRNA gene polymerase chain reaction DNA amplification covering V3-V9; probe labelling by single nucleotide extension and signal detection. The levels of short-chain fatty acids (SCFAs) were determined by gas chromatography and flame ionization. RESULTS: There was no sex difference in the response to FMT either in the placebo group or active treated group. There was no difference between females and males in either the placebo group or actively treated groups in the total score on the IBS-SSS, FAS or IBS-QoL, in dysbiosis, or in the faecal bacteria or SCFA level. However, the response rate was significantly higher in females with diarrhoea-predominant (IBS-D) than that of males at 1 mo, and 3 mo after FMT. Moreover, IBS-SSS total score was significantly lower in female patients with IBS-D than that of male patients both 1 mo and 3 mo after FMT. CONCLUSION: There was no sex difference in the response to FMT among IBS patients with moderate-to-severe symptoms who had previously not responded to NICE-modified diet. However, female patients with IBS-D respond better and have higher reduction of symptoms than males after FMT.


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Europa (Continente) , Transplante de Microbiota Fecal/efeitos adversos , Fezes , Feminino , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/terapia , Masculino , Qualidade de Vida , RNA Ribossômico 16S
5.
Lett Appl Microbiol ; 73(2): 149-158, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33864273

RESUMO

Clostridioides difficile is a major cause of health-care related infections and antibiotic-associated diarrhea. High recurrence rates following antibiotic treatment, along with the emergence of hypervirulent and multidrug resistant ribotypes makes essential the development of safe, effective, novel therapies for the treatment of C. difficile infections. The primary outcome evaluated in this meta-analysis was the effectiveness of fecal microbiota transplantation (FMT). Secondary outcomes were the proportion of patients suffering adverse effects along with the most effective administration route. The mean treatment effectiveness was 82% (95% CI: 75-89). Overall, patients receiving FMT via colonoscopy experienced more adverse effects than patients whom received enema, or oral capsules (71·6% vs 40·2%, and 35·3% respectively). Comparing administration of FMT by colonoscopy versus enema resulted in a Hedges' g of -0·74 (95% CI of -0·9 to -0·58), indicating a slight advantage in favor of colonoscopy. The comparison between colonoscopy and capsule returned a Hedges' g of 0·44 (95% CI of 0·20-0·69), indicating that delivery of the FMT by capsule was statistically significantly more effective. FMT provides an effective and safe treatment for C. difficile diarrhea. Further research into the efficacy of different preparation protocols is needed.


Assuntos
Infecções por Clostridium/terapia , Diarreia/terapia , Transplante de Microbiota Fecal/métodos , Administração Oral , Cápsulas/administração & dosagem , Clostridioides difficile , Infecções por Clostridium/microbiologia , Diarreia/microbiologia , Enema , Transplante de Microbiota Fecal/efeitos adversos , Microbioma Gastrointestinal , Humanos , Resultado do Tratamento
6.
Int J Mol Sci ; 22(6)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809421

RESUMO

COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut-lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.


Assuntos
COVID-19/epidemiologia , Transplante de Microbiota Fecal/métodos , Pandemias , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal/efeitos adversos , Microbioma Gastrointestinal , Humanos , Pulmão/fisiopatologia , Resultado do Tratamento
7.
Medicine (Baltimore) ; 100(14): e25390, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832129

RESUMO

OBJECTIVE: Functional constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. Combined therapy uniting multiple treatments may be promising. Fecal microbiota transplantation (FMT) which tends to be an etiological treatment has been increasingly investigated in its management. Meanwhile, laxatives are widely used to relieve constipation temporarily, but their overall efficacy is poor. Therefore, we performed meta-analyses of randomized controlled trials to evaluate the joint efficacy of FMT and laxatives in functional constipation. METHODS: We performed a systematic literature search of 6 electronic databases as of August 11, 2020. Randomized controlled trial of FMT together with laxatives vs laxatives alone in functional constipation in adults were included. Two reviewers independently performed the screening, data extraction, and bias assessment. Dichotomous outcome data were synthesized by risk ratio, and measurement data by weighted mean difference (WMD). RESULTS: A total of 1400 records were identified, of which 5 were eligible (409 patients). Overall, compared to laxatives alone, combined therapy of FMT and laxatives more significantly improved total effective rate (risk ratio: 1.35; 95% confidence interval [CI]: 1.14, 1.60; I2 = 13%), Bristol stool form scale score (WMD: 1.04; 95% CI: 0.57, 1.51; I2 = 76%), reduce Wexner score (WMD: -3.25; 95% CI: -5.58, -0.92; I2 = 92%), Knowles-Eccersley-Scott-Symptom (KESS) score (WMD: -5.65; 95% CI: -7.62, -3.69; I2 = 0%) and patient assessment of constipation quality of life score (WMD: -18.56; 95%; CI: -26.43, -10.68; I2 = 78%). No serious adverse events were reported. The majority of included studies had poor methodological quality. CONCLUSION: Combined therapy of FMT and laxatives may be a reasonably effective and safe treatment for people with functional constipation. However, caution is needed with the interpretation of these data due to the small sample size, high heterogeneity, and low quality of the studies. Besides, we expect that more studies will be performed exploring the efficacy and safety of combined therapy for functional constipation.


Assuntos
Terapia Combinada/métodos , Constipação Intestinal/fisiopatologia , Constipação Intestinal/terapia , Transplante de Microbiota Fecal/métodos , Laxantes/uso terapêutico , Adulto , Idoso , Estudos de Casos e Controles , China/epidemiologia , Terapia Combinada/efeitos adversos , Constipação Intestinal/psicologia , Gerenciamento de Dados , Transplante de Microbiota Fecal/efeitos adversos , Feminino , Humanos , Laxantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
8.
J Clin Gastroenterol ; 55(4): 300-308, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33471490

RESUMO

GOALS: We performed a systematic review with meta-analysis to examine the efficacy and safety of oral fecal microbiota transplantation (FMT) capsules for recurrent Clostridioides difficile infection (rCDI). BACKGROUND: FMT through colonoscopy is established as effective and safe in treating multiple recurrences of CDI, but consensus has not been established on delivery through oral capsules. STUDY: A systematic literature search was performed with multiple databases including MEDLINE and EMBASE to identify original studies including at least 10 patients that investigated the role of oral FMT capsules to treat rCDI. Cure rates were pooled by a random effects model and publication bias was assessed with the Egger test. Secondary analyses assessed for differences between capsule preparation (frozen vs. lyophilized stool) and delivery modality (capsule vs. colonoscopy). RESULTS: Fifteen studies (12 case series and 3 randomized controlled trials) encompassing 763 patients were identified for inclusion. Significant variability existed in baseline patient characteristics and protocols. Meta-analysis of proportions showed efficacy of oral FMT capsules to be 0.821 (95% confidence interval: 0.762-0.874). No evidence for publication bias was found (P=0.51). Secondary analyses did not find significant differences in efficacy. Fourteen adverse events leading to death or hospitalization were noted, none of which were attributed to FMT. CONCLUSIONS: Oral FMT capsules for rCDI are promising because of ease of administration and noninvasive delivery. We found an overall efficacy of 82.1% with a low rate of serious adverse events. Further studies are needed to optimize protocols and outcomes.


Assuntos
Infecções por Clostridium , Transplante de Microbiota Fecal , Cápsulas , Clostridioides , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal/efeitos adversos , Humanos , Recidiva Local de Neoplasia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Resultado do Tratamento
9.
Gastroenterology ; 160(6): 1961-1969.e3, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33444573

RESUMO

BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI), with emerging data on intermediate and long-term safety. METHODS: A prospective survey-based study was conducted (September 2012-June 2018) in patients undergoing FMT for recurrent CDI. Data on demographics and comorbidities were abstracted from medical records. Patients were contacted at 1 week, 1 month, 6 months, 1 year (short-term), and ≥2 years post-FMT (long-term). Symptoms and new medical diagnoses were recorded at each time point. Data were weighted to account for survey nonresponse bias. Multivariate logistic regression models for adverse events were built using age (per 10-year increment), sex, time of survey, and comorbidities. P < .05 was considered statistically significant. RESULTS: Overall, 609 patients underwent FMT; median age was 56 years (range, 18-94), 64.8% were women, 22.8% had inflammatory bowel disease (IBD). At short-term follow-up (n = 609), >60% of patients had diarrhea and 19%-33% had constipation. At 1 year, 9.5% reported additional CDI episodes. On multivariable analysis, patients with IBD, dialysis-dependent kidney disease, and multiple FMTs had higher risk of diarrhea; risk of constipation was higher in women and lower in IBD (all P < .05). For long-term follow-up (n = 447), median time of follow-up was 3.7 years (range, 2.0-6.8). Overall, 73 new diagnoses were reported: 13% gastrointestinal, 10% weight gain, 11.8% new infections (all deemed unrelated to FMT). Median time to infections was 29 months (range, 0-73) post-FMT. CONCLUSION: FMT appears safe with low risk of transmission of infections. Several new diagnoses were reported, which should be explored in future studies.


Assuntos
Clostridioides difficile , Constipação Intestinal/etiologia , Diarreia/etiologia , Enterocolite Pseudomembranosa/terapia , Transplante de Microbiota Fecal/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Enterocolite Pseudomembranosa/complicações , Enterocolite Pseudomembranosa/tratamento farmacológico , Transplante de Microbiota Fecal/estatística & dados numéricos , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Estudos Prospectivos , Recidiva , Fatores de Risco , Sepse/epidemiologia , Inquéritos e Questionários , Fatores de Tempo , Infecções Urinárias/epidemiologia , Ganho de Peso , Adulto Jovem
10.
Aliment Pharmacol Ther ; 53(1): 33-42, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33159374

RESUMO

BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment in C. difficile infection (CDI) and is currently being investigated in other diseases. There is concern around the safety of FMT and that side effects or complications may be under-reported in the medical literature. AIM: To evaluate the safety of FMT by summarising the overall reported Adverse Events (AEs) over a 20-year period METHODS: We searched EMBASE, MEDLINE, and Cochrane Library databases, and CNKI and Wanfang Data from January 2000 to April 2020. All original studies reporting FMT-related AEs were considered for inclusion. FMT-related AEs were further classified as delivery-related or microbiota-related. RESULTS: Based on the inclusion criteria, 129 studies, which included 4241 patients (5688 FMT courses), were finally eligible. The most common indication for FMT was CDI. Overall, FMT-related AEs were observed in 19% of FMT procedures. The most frequently reported FMT-related AEs were diarrhoea (10%) and abdominal discomfort/pain/cramping (7%). FMT-related serious adverse events (SAEs), including infections and deaths, have been reported in 1.4% of patients who underwent FMT (0.99% microbiota-related SAEs). Four of five FMT-related deaths were reported in patients receiving FMT via the upper gastrointestinal route. Importantly, all reported FMT-related SAEs were in patients with mucosal barrier injury. CONCLUSION: Most FMT-related AEs were mild or moderate and self-limiting. Although FMT appears to be highly safe, its methodology should be improved to reduce both delivery-related AEs and, microbiota-related AEs.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/terapia , Diarreia/epidemiologia , Diarreia/etiologia , Diarreia/terapia , Transplante de Microbiota Fecal/efeitos adversos , Fezes , Humanos , Incidência , Recidiva , Resultado do Tratamento
11.
Science ; 371(6529): 602-609, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33303685

RESUMO

The gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Transplante de Microbiota Fecal/efeitos adversos , Microbioma Gastrointestinal , Melanoma/terapia , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/terapia , Adulto , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Imunoterapia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
13.
Gut Microbes ; 12(1): 1-25, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33345703

RESUMO

The intestinal microbiome has been identified as a key modifier for a variety of health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a fast, safe, and effective means by which to modify the intestinal microbiome and potentially treat a variety of health conditions. Despite extensive research of FMT for CDI, there is a lack of clarity informed by systematic synthesis of data regarding the safety and efficacy of FMT for other health conditions. This systematic review used PRISMA guidelines and was prospectively registered with PROSPERO (CRD42018104243). In March 2020, a search of MEDLINE, EMBASE, and PsycINFO was conducted. We identified 26 eligible studies. A meta-analysis of FMT for active Ulcerative Colitis (UC) showed that FMT significantly improved rates of clinical remission (OR = 3.634, 95% CI = 1.940 to 6.808, I2 = 0%, p < .001), clinical response (OR = 2.634, 95% CI = 1.441 to 4.815, I2 = 33%, p = .002) and endoscopic remission (OR = 4.431, 95% CI = 1.901 to 10.324, I2 = 0%, p = .001). With respect to Irritable Bowel Syndrome, a meta-analysis showed no significant change in symptoms following FMT (p = .739). Hepatic disorders, metabolic syndrome, and antibiotic-resistant organisms were conditions with emerging data on FMT. Serious adverse events (AE) were more often reported in control group participants (n = 43) compared with FMT group participants (n = 26). There were similar rates of mild to moderate AE in both groups. Preliminary data suggest that FMT is a potentially safe, well-tolerated and efficacious treatment for certain conditions other than CDI, with evidence for active UC being the most compelling.


Assuntos
Colite Ulcerativa/terapia , Transplante de Microbiota Fecal/métodos , Síndrome do Intestino Irritável/terapia , Hepatopatias/terapia , Síndrome Metabólica/terapia , Obesidade/terapia , Farmacorresistência Bacteriana/genética , Transplante de Microbiota Fecal/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Humanos , Resultado do Tratamento
14.
JAMA Netw Open ; 3(12): e2030415, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33346848

RESUMO

Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants: This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and Relevance: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Obesidade Pediátrica , Qualidade de Vida , Adolescente , Índice de Massa Corporal , Método Duplo-Cego , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/métodos , Feminino , Humanos , Masculino , Monitorização Fisiológica/métodos , Nova Zelândia , Obesidade Pediátrica/metabolismo , Obesidade Pediátrica/fisiopatologia , Obesidade Pediátrica/psicologia , Obesidade Pediátrica/terapia , Resultado do Tratamento
15.
PLoS One ; 15(9): e0238910, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32946509

RESUMO

OBJECTIVES: Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease. METHODS: Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted. RESULTS: Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn's disease patients seemed to benefit more from the procedure. CONCLUSIONS: The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn's disease.


Assuntos
Transplante de Microbiota Fecal/métodos , Doenças Inflamatórias Intestinais/terapia , Transplante de Microbiota Fecal/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Resultado do Tratamento
16.
Medicine (Baltimore) ; 99(35): e22035, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871960

RESUMO

Imbalances in the gut microbiota mediate the progression of neurodegenerative diseases such as Parkinson's disease (PD). Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for PD. The objective of this study was to assess the efficacy and safety of FMT on PD. Fifteen PD patients were included, 10 of them received FMT via colonoscopy (colonic FMT group) and 5 received FMT via nasal-jejunal tube (nasointestinal FMT group). The score of PSQI, HAMD, HAMA, PDQ-39, NMSQ and UPDRS-III significantly decreased after FMT treatment (all P < .05). Colonic FMT group showed significant improvement and longer maintenance of efficacy compared with nasointestinal FMT (P = .002). Two patients achieved self-satisfying outcomes that last for more than 24 months. However, nasointestinal FMT group had no significant therapeutic effect, although UPDRS-III score slightly reduced. There were no patients were satisfied with nasointestinal FMT for more than 3 months. Among 15 PD patients, there were 5 cases had adverse events (AEs), including diarrhea (2 cases), abdominal pain (2 cases) and flatulence (1 case). These AEs were mild and self-limiting. We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable.


Assuntos
Transplante de Microbiota Fecal/estatística & dados numéricos , Doença de Parkinson/terapia , Idoso , Colonoscopia , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/métodos , Feminino , Humanos , Intubação Gastrointestinal , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Projetos Piloto , Adulto Jovem
18.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(5): 509-515, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32842434

RESUMO

Fecal microbiota transplant (FMT) has become an effective method for the treatment of recurrent C. difficile infection. In addition, it has shown certain effects in other diseases inside and outside the intestine. A large number of clinical trials have been carried out. However, there is still lack of uniform standard for strategies of FMT. In this paper, we discussed the current hot and controversial issues of FMT from the aspects of indication, donor screening, fecal suspension quality control, methodology, follow-up and efficacy judgment, treatment of adverse reaction and ethical supervision based on our team's clinical experience.


Assuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal/métodos , Seleção do Doador , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/normas , Fezes/microbiologia , Humanos , Resultado do Tratamento
20.
Exp Neurol ; 334: 113439, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32835671

RESUMO

Obstructive sleep apnea (OSA) is a chronic prevalent condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). Evidence suggests that OSA can alter the gut microbiome (GM) diversity and composition that may then promote the occurrence of some of the OSA-associated morbidities. However, it is unclear whether perturbations in the GM caused by IH can elicit sleep disturbances that underlie the increased sleep propensity that occurs in IH-exposed mice. To evaluate this issue, we exposed C57Bl/6 J mice to IH or room air (RA) for 6 weeks, and fecal matter was collected and frozen. C57Bl/6 J naïve mice were then randomly assigned to a fecal microbiota transfer (FMT) protocol for 3 weeks with either IH or RA fecal slur, and their GM was then analyzed using 16 s rRNA sequencing. In addition, FMT recipients underwent sleep recordings using piezoelectric approaches for 3 consecutive days. As anticipated, FMT-IH and FMT-RA mice showed different taxonomic profiles that corresponded to previous effects of IH on GM. Furthermore, FMT-IH mice exhibited increased sleep duration and the frequency of longer sleep bouts during the dark cycle, suggesting increased sleepiness (p < 0.0001 vs. FMT-RA mice). Thus, alterations of GM diversity induced by IH exposures can elicit sleep disturbances in the absence of concurrent IH, suggesting that sleep disturbances can be mediated, at least in part, by IH-induced alterations in GM.


Assuntos
Transplante de Microbiota Fecal/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Hipóxia/complicações , Hipóxia/fisiopatologia , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/fisiopatologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL
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