BACKGROUND: Fecal microbiota transplantation is an effective treatment for many gastrointestinal diseases, such as Clostridium difficile infection and inflammatory bowel disease, especially ulcerative colitis. Changes in colonic microflora may play an important role in the pathogenesis of ulcerative colitis, and improvements in the intestinal microflora may relieve the disease. Fecal bacterial transplants and oral probiotics are becoming important ways to relieve active ulcerative colitis.
PURPOSE: This systematic review with meta-analysis compared the efficacy and safety of basic treatment combined with fecal microbiota transplantation or mixed probiotics therapy in relieving mild to moderate ulcerative colitis.
METHODS: The PubMed, Embase, and Cochrane libraries (updated September 2019) were searched to identify randomized, placebo-controlled, or head-to-head trials assessing fecal microbiota transplantation or probiotic VSL#3 as induction therapy in active ulcerative colitis. We analyze data using the R program to obtain evidence of direct comparison and to generate intermediate variables for indirect treatment comparisons.
RESULTS: Seven randomized, double-blind, placebo-controlled trials were used as the sources of the induction data. All treatments were superior to placebo. In terms of clinical remission and clinical response to active ulcerative colitis, direct comparisons showed fecal microbiota transplantation (OR = 3.47, 95% CI = 1.93-6.25) (OR = 2.48, 95% CI = 1.18-5.21) and mixed probiotics VSL#3 (OR = 2.40, 95% CI = 1.49-3.88) (OR = 3.09, 95% CI = 1.53-6.25) to have better effects than the placebo. Indirect comparison showed fecal microbiota transplantation and probiotic VSL#3 did not reach statistical significance either in clinical remission (RR = 1.20, 95% CI = 0.70-2.06) or clinical response (RR = 0.95, 95% CI = 0.62-1.45). In terms of safety, fecal microbiota transplantation (OR = 1.15, 95% CI = 0.51-2.61) and VSL #3 (OR = 0.90, 95% CI = 0.33-2.49) showed no statistically significant increase in adverse events compared with the control group. In terms of serious adverse events, there was no statistical difference between the fecal microbiota transplantation group and the control group (OR = 1.29, 95% CI = 0.46-3.57). The probiotics VSL#3 seems more safer than fecal microbiota transplantation, because serious adverse events were not reported in the VSL#3 articles.
CONCLUSIONS: Fecal microbiota transplantation or mixed probiotics VSL#3 achieved good results in clinical remission and clinical response in active ulcerative colitis, and there was no increased risk of adverse reactions. There was no statistical difference between the therapeutic effect of fecal microbiota transplantation and that of mixed probiotics VSL#3. However, the use of fecal microbiota transplantation and probiotics still has many unresolved problems in clinical applications, and more randomized controlled trials are required to confirm its efficacy.
Background. Fecal microbiota transplantation (FMT) is an emerging treatment approach for inflammatory bowel disease (IBD). The donor selection, the separation of fecal bacteria, the frequency of FMT, the way of infusion, the long-term safety, and efficacy are still uncertain. Aim. To further study the efficacy and safety and protocol of FMT for IBD. Methods. A systematic review and meta-analysis were conducted until February, 2018. Clinical remission was established as the primary outcome. Results. A total of 596 paediatric and adult IBD patients were enrolled, and 459 patients received FMT therapy. 28.8% (132/459) patients achieved clinical remission during follow-up. 53% (241/459) patients achieved clinical response. The pooled estimated clinical remission for ulcerative colitis (UC) was 21% (95% CI: 8%-37%) and 30% (95% CI: 11%-52%) for Crohn’s disease (CD), both with a risk of heterogeneity; 10% (95% CI: 0%-43%) for paediatric UC; 26% (95% CI: 10%-48%) for adult UC; 45% for paediatric CD (95% CI: 24%-66%); 22% (95% CI: 3%-52%) for adult CD. Meta-analysis of cohort studies showed that moderate-severe IBD patients could achieve more significant remission from FMT than mild-moderate patients (P=0.037). Delivery route has no impact on the efficacy of FMT in UC and CD. Based on current available evidence, a trend was observed towards higher clinical remission rate of frozen stool FMT than that of fresh stool for UC, while there was no significant difference between fresh and frozen FMT for CD. The optimal donor stool for FMT is still uncertain. Meta-analysis of RCTs showed that FMT treatment achieved significantly higher clinical remission rate than placebo for UC (28% versus 9%, P=0.0003). Conclusion. FMT is an effective and safe therapy for both paediatric and adult IBD; fresh or frozen donor stool, delivery route, and antibiotic pretreatment or not have no impact on the efficacy of FMT in IBD. FMT might be a potential rescue therapy and even an initial standardized therapy for IBD. However, few data exist on long-term safety and efficacy and further validation is needed.
BACKGROUND: Changes in the colonic microbiota may play a role in the pathogenesis of ulcerative colitis (UC) and restoration of healthy gut microbiota may ameliorate disease. A systematic review and meta-analysis was conducted to assess fecal microbiota transplantation (FMT) as a treatment for active UC.
METHODS: A literature search was conducted to identify high-quality studies of FMT as a treatment for patients with UC. The primary outcome was combined clinical remission and endoscopic remission or response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Odds ratios with 95% confidence intervals (CIs) are reported.
RESULTS: Overall, 4 studies with 277 participants were eligible for inclusion. Among 4 randomized controlled trials, FMT was associated with higher combined clinical and endoscopic remission compared with placebo (risk ratio UC not in remission was 0.80; 95% CI: 0.71-0.89) with a number needed to treat of 5 (95% CI: 4-10). There was no statistically significant increase in serious adverse events with FMT compared with controls (risk ratio adverse event was 1.4; 95% CI: 0.55-3.58).
CONCLUSIONS: Among randomized controlled trials, short-term use of FMT shows promise as a treatment to induce remission in active UC based on the efficacy and safety observed. However, there remain many unanswered questions that require further research before FMT can be considered for use in clinical practice.
El trasplante de microbiota fecal (FMT) está emergiendo como una nueva terapia para la colitis ulcerosa (UC). La interpretación de la eficacia de la FMT para la UC se complica por las diferencias entre los estudios de cegamiento, los procedimientos de administración de FMT, la intensidad de la terapia y los métodos de procesamiento de las heces de los donantes. OBJETIVO: Determinar si la FMT es efectiva y segura para la inducción de la remisión en UC activa. Métodos: Medline (Ovid), Embase y la Cochrane Library se realizaron búsquedas desde el inicio hasta febrero de 2017. Se incluyeron estudios originales que informaron tasas de remisión después de FMT para UC activa. Todos los diseños del estudio se incluyeron en la revisión sistemática y un metanálisis realizado incluyendo sólo ensayos controlados aleatorios (ECA). RESULTADOS: Hubo 14 estudios de cohortes y cuatro ECA que utilizaron protocolos marcadamente diferentes. En el metanálisis de ECA, la remisión clínica se logró en 39 de 140 (28%) pacientes en los grupos de FMT donantes, en comparación con 13 de 137 (9%) pacientes en los grupos placebo; Odds ratio 3,67 (IC del 95%: 1,82 - 7,39, P <0,01). La respuesta clínica se logró en 69 de 140 (49%) pacientes FMT donantes en comparación con 38 de 137 (28%) pacientes con placebo; Odds ratio 2,48 (IC del 95%: 1,18 - 5,21, p = 0,02). En los estudios de cohortes, 39 de 168 (24%, IC del 95%: 11% -40%) lograron la remisión clínica. CONCLUSIONES: A pesar de la variación en los procesos, la FMT parece ser eficaz para la inducción de la remisión en la UC, sin señales de seguridad a corto plazo importantes. Se necesitan más estudios para definir mejor la frecuencia de las dosis y los métodos de preparación y explorar su viabilidad, eficacia y seguridad como agente de mantenimiento.
El trasplante de microbiota fecal (FMT) ha sido investigado como un posible tratamiento para la enfermedad inflamatoria intestinal (EII). Por lo tanto, realizó una revisión sistemática y meta-análisis de evaluación de la eficacia y la seguridad de FMT en la EII. Métodos Se realizó una revisión sistemática hasta enero de 2017. Se excluyeron los estudios si los pacientes tenían co-infección o los datos se agruparon entre los subtipos de la enfermedad (colitis ulcerosa (UC), enfermedad de Crohn (CD), pouchitis). La remisión clínica se estableció como el resultado primario. Se obtuvieron tamaños de efecto agrupados e intervalos de confianza del 95% usando el modelo de efectos aleatorios. RESULTADOS: Se incluyeron 53 estudios (41 en UC, 11 en CD, 4 en pouchitis). En general, el 36% (201/555) de la CU, el 50,5% (42/83) de la CD y el 21,5% (5/23) de los pacientes con pouchitis alcanzaron la remisión clínica. Entre los estudios de cohorte, la proporción agrupada que alcanzó la remisión clínica fue de 33% (IC del 95%: 23% -43%) para UC y 52% (IC del 95%: 31% -72%) para DC, ambos con riesgo moderado de heterogeneidad. Para 4 ECA en UC, se observó un beneficio significativo en la remisión clínica (P-OR = 2,89, IC del 95% = 1,36-6,13, P = 0,006) con heterogeneidad moderada (Q de Cochran, 0,188; I2 = 37%). Los subanálisis sugieren que la remisión en UC mejoró con un mayor número de infusiones de FMT y una menor administración del tracto gastrointestinal. La mayoría de los eventos adversos fueron trastornos gastrointestinales transitorios. Microbiota análisis se realizó en 24 estudios, con muchos de ellos la identificación de una mayor diversidad y un cambio en el receptor microbiota perfil hacia el donante post-FMT. Conclusiones: La FMT parece eficaz en la inducción de la remisión de la UC, pero la durabilidad y la seguridad a largo plazo no están claras. Se necesitan estudios controlados adicionales bien diseñados de FMT en IBD, especialmente en CD y pouchitis.
Fecal microbiota transplantation is an effective treatment for many gastrointestinal diseases, such as Clostridium difficile infection and inflammatory bowel disease, especially ulcerative colitis. Changes in colonic microflora may play an important role in the pathogenesis of ulcerative colitis, and improvements in the intestinal microflora may relieve the disease. Fecal bacterial transplants and oral probiotics are becoming important ways to relieve active ulcerative colitis.
PURPOSE:
This systematic review with meta-analysis compared the efficacy and safety of basic treatment combined with fecal microbiota transplantation or mixed probiotics therapy in relieving mild to moderate ulcerative colitis.
METHODS:
The PubMed, Embase, and Cochrane libraries (updated September 2019) were searched to identify randomized, placebo-controlled, or head-to-head trials assessing fecal microbiota transplantation or probiotic VSL#3 as induction therapy in active ulcerative colitis. We analyze data using the R program to obtain evidence of direct comparison and to generate intermediate variables for indirect treatment comparisons.
RESULTS:
Seven randomized, double-blind, placebo-controlled trials were used as the sources of the induction data. All treatments were superior to placebo. In terms of clinical remission and clinical response to active ulcerative colitis, direct comparisons showed fecal microbiota transplantation (OR = 3.47, 95% CI = 1.93-6.25) (OR = 2.48, 95% CI = 1.18-5.21) and mixed probiotics VSL#3 (OR = 2.40, 95% CI = 1.49-3.88) (OR = 3.09, 95% CI = 1.53-6.25) to have better effects than the placebo. Indirect comparison showed fecal microbiota transplantation and probiotic VSL#3 did not reach statistical significance either in clinical remission (RR = 1.20, 95% CI = 0.70-2.06) or clinical response (RR = 0.95, 95% CI = 0.62-1.45). In terms of safety, fecal microbiota transplantation (OR = 1.15, 95% CI = 0.51-2.61) and VSL #3 (OR = 0.90, 95% CI = 0.33-2.49) showed no statistically significant increase in adverse events compared with the control group. In terms of serious adverse events, there was no statistical difference between the fecal microbiota transplantation group and the control group (OR = 1.29, 95% CI = 0.46-3.57). The probiotics VSL#3 seems more safer than fecal microbiota transplantation, because serious adverse events were not reported in the VSL#3 articles.
CONCLUSIONS:
Fecal microbiota transplantation or mixed probiotics VSL#3 achieved good results in clinical remission and clinical response in active ulcerative colitis, and there was no increased risk of adverse reactions. There was no statistical difference between the therapeutic effect of fecal microbiota transplantation and that of mixed probiotics VSL#3. However, the use of fecal microbiota transplantation and probiotics still has many unresolved problems in clinical applications, and more randomized controlled trials are required to confirm its efficacy.
