Impact Of Fecal Microbiota Transplantation Research Articles

Parkinson’s Disease and the faecal microbiota transplantation. Review of current knowledge

Introduction and Purpose. Parkinson’s Disease (PD) is a chronic neurodegenerative disorder caused by dopamine deficiency due to neuronal degeneration, leading to motor and non-motor symptoms. Gastrointestinal symptoms are common and often precede motor symptoms. There is increasing evidence that imbalanced gut microbiota may influence the gut-brain axis and contribute to motor and non-motor PD symptoms. Fecal microbiota transplantation (FMT) may have the potential to restore gut flora and improve PD symptoms. The study aims to explore the current knowledge on the impact of FMT on PD symptoms, acknowledging existing reviews and highlighting new studies not yet reviewed. Understanding the underlying causes of PD could lead to better treatment, diagnostics, and prevention.State of knowledge. PD patients suffer from specific gut dysbiosis which leads to imbalance in the produced pro- and anti-inflammatory substances in the intestinal lumen resulting in aggreviation of α-synuclein in gut nervous cells which may hypothetically transfer via vagal nerve to CNS causing PD. In animal research FMT showed promising results in alleviating PD symptoms. Case reports showed reduction of both motor and non-motor dysfunctions, especially in constipation. DuPont et al. showed improvements in constipation, motor deficits, overall Parkinson’s symptoms, and some non-motor disorders. Cheng et al. showed improvements in MDS-UPDRS, scores of GI tract symptoms scales, PD-related autonomic symptoms and the stool frequency. Bruggeman et al. showed better MDS-UPDRS part 3 scores and better colon transit, but no significant differencies in any other tested domains. Conclusions. As there is yet no standarized protocol for FMT, all of the past research used different techniques and showed slightly different outcomes, but all have shown that FMT have some positive effects on PD symptoms.

Impact of fecal microbiota transplantation in severe alcoholic hepatitis: A systematic review and meta-analysis.

Severe alcoholic hepatitis (SAH) is a serious condition with few treatments. By modifying the gut-liver axis, fecal microbiota transplantation (FMT) was proposed as a treatment for SAH. The purpose of this meta-analysis was to evaluate the efficacy of FMT versus the standard of care (SOC) in improving SAH patient survival rates. A thorough search of electronic databases was conducted till September 2023. The survival rates of SAH patients undergoing FMT versus SOC were compared. Using Review Manager 5.4, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The meta-analysis consisted of six studies with a total of 371 patients with SAH. Patients who received FMT had significantly higher survival rates at 1 and 3 months compared to those who received SOC, with pooled OR of 2.91 (95% CI: 1.56-5.42, P = 0.0008) and 3.07 (95% CI: 1.81-5.20, P < 0.0001), respectively. However, the survival advantage disappeared after 6 months (OR: 2.96, 95% CI: 0.99-8.85, P = 0.05) and 1 year of follow-up (OR: 1.81, 95% CI: 0.44-7.46, P = 0.41). This meta-analysis highlights the potential of FMT to significantly improve short-term survival rates in SAH patients. However, the survival benefit did not last 6-12 months. These findings call for additional research into the effectiveness of FMT over the long term, along with strategies for extending the survival benefit.

The Impact of Fecal Microbiota Transplantation on the Intestinal Microecology of Patients with Colorectal Cancer

This study investigated the impact of fecal microbiota transplantation (FMT) on the intestinal microecology of patients with colorectal cancer. The intestinal microbiota structure of patients with colorectal cancer often undergoes significant changes, which are closely related to the occurrence and development of the disease. As a novel therapeutic approach, FMT aims to rebuild intestinal microecological balance and thereby improve clinical symptoms and prognosis of patients with colorectal cancer. This study found that FMT can effectively alter the intestinal microbiota structure of patients with colorectal cancer, increase microbial diversity, reduce intestinal inflammation, and potentially enhance the patient s immune function. However, FMT still faces challenges in clinical application, such as donor selection, ethical issues, and the stability of transplantation effects. Future research needs to further explore optimization strategies for FMT to fully realize its potential in the treatment of colorectal cancer.

Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility.

The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear. We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation. In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.

Efficacy of fecal microbiota transplantation in patients with Parkinson’s disease: clinical trial results from a randomized, placebo-controlled design

ABSTRACT The occurrence and development of Parkinson’s disease (PD) have been demonstrated to be related to gut dysbiosis, however, the impact of fecal microbiota transplantation (FMT) on microbiota engraftment in PD patients is uncertain. We performed a randomized, placebo-controlled trial at the Department of Neurology, Army Medical University Southwest Hospital in China (ChiCTR1900021405) from February 2019 to December 2019. Fifty-six participants with mild to moderate PD (Hoehn-Yahr stage 1–3) were randomly assigned to the FMT and placebo group, 27 patients in the FMT group and 27 in the placebo group completed the whole trial. During the follow-up, no severe adverse effect was observed, and patients with FMT treatment showed significant improvement in PD-related autonomic symptoms compared with the placebo group at the end of this trial (MDS-UPDRS total score, group×time effect, B = -6.56 [−12.98, −0.13], P < 0.05). Additionally, FMT improved gastrointestinal disorders and a marked increase in the complexity of the microecological system in patients. This study demonstrated that FMT through oral administration is clinically feasible and has the potential to improve the effectiveness of current medications in the clinical symptoms of PD patients.

Fecal Microbiota Transplantation in Liver Cirrhosis.

The human gastrointestinal tract houses a diverse array of probiotic and pathogenic bacteria and any alterations in this microbial composition can exert a significant influence on an individual's well-being. It is well-established that imbalances in the gut microbiota play a pivotal role in the development of liver diseases. In light of this, a new adjuvant therapy for liver diseases could be regulating the intestinal microbiota. Through fecal microbiota transplantation, patients whose microbiomes are compromised are treated with stool from healthy donors in an attempt to restore a normal microbiome and alleviate their symptoms. A review of cross-sectional studies and case reports suggests that fecal microbiota transplants may offer effective treatment for chronic liver diseases. Adding to the potential of this emerging therapy, recent research has indicated that fecal microbiota transplantation holds promise as a therapeutic approach specifically for liver cirrhosis. By introducing a diverse range of beneficial microorganisms into the gut, this innovative treatment aims to address the microbial imbalances often observed in cirrhotic patients. While further validation is still required, these preliminary findings highlight the potential impact of fecal microbiota transplantation as a novel and targeted method for managing liver cirrhosis. We aimed to summarize the current state of understanding regarding this procedure, as a new therapeutic method for liver cirrhosis, as well as to explain its clinical application and future potential.

Surgical Prehabilitation in Patients with Gastrointestinal Cancers: Impact of Unimodal and Multimodal Programs on Postoperative Outcomes and Prospects for New Therapeutic Strategies-A Systematic Review.

The advantages of prehabilitation in surgical oncology are unclear. This systematic review aims to (1) evaluate the latest evidence of preoperative prehabilitation interventions on postoperative outcomes after gastrointestinal (GI) cancer surgery and (2) discuss new potential therapeutic targets as part of prehabilitation. Randomized controlled trials published between January 2017 and August 2022 were identified through Medline. The population of interest was oncological patients undergoing GI surgery. Trials were considered if they evaluated prehabilitation interventions (nutrition, physical activity, probiotics and symbiotics, fecal microbiota transplantation, and ghrelin receptor agonists), alone or combined, on postoperative outcomes. Out of 1180 records initially identified, 15 studies were retained. Evidence for the benefits of unimodal interventions was limited. Preoperative multimodal programs, including nutrition and physical activity with or without psychological support, showed improvement in postoperative physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. No trial evaluated the impact of fecal microbiota transplantation or oral ghrelin receptor agonists. Further studies are needed to confirm our findings, identify patients who are more likely to benefit from surgical prehabilitation, and harmonize interventions.

Intestinal microbiota changes pre- and post-fecal microbiota transplantation for treatment of recurrent Clostridioides difficile infection among Iranian patients with concurrent inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at a greater risk for the recurrence of Clostridioides difficile infection (rCDI) that is triggered by intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) has emerged as a highly effective therapeutic option for this complication. However, little is known about the impact of FMT on intestinal microbiota alterations in rCDI patients suffering from IBD. In this study, we aimed to investigate post-FMT intestinal microbiota alterations in Iranian rCDI patients with underlying IBD. A total of 21 fecal samples were collected including 14 samples pre- and post-FMT and 7 samples from healthy donors. Microbial analysis was performed by quantitative real-time PCR (RT-qPCR) assay targeting the 16S rRNA gene. The pre-FMT profile and composition of the fecal microbiota were compared to the microbial changes of samples collected 28 days after FMT. Overall, the fecal microbiota profile of recipients was more similar to donor samples after the transplantation. We observed a significant increase in the relative abundance of Bacteroidetes post-FMT, compared to the pre-FMT microbial profile. Furthermore, there were remarkable differences between the microbial profile of pre-FMT, post-FMT, and healthy donor samples by PCoA analysis based on the ordination distance. This study demonstrates FMT as a safe and effective approach to restore the indigenous composition of the intestinal microbiota in rCDI patients and ultimately results in the treatment of concurrent IBD.

Washed microbiota transplantation improves patients with metabolic syndrome in South China.

Metabolic syndrome (MS) is a growing public health problem worldwide. The clinical impact of fecal microbiota transplantation (FMT) from healthy donors in MS patients is unclear, especially in southern Chinese populations. This study aimed to investigate the effect of washed microbiota transplantation (WMT) in MS patients in southern China. The clinical data of patients with different indications receiving 1-3 courses of WMT were retrospectively collected. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared, such as fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c)), high-density lipoprotein cholesterol (HDL-c), non-high-density lipoprotein (non-HDL-c), systolic blood pressure (SBP), diastolic blood pressure (DBP), etc. At the same time, comprehensive efficacy evaluation and atherosclerotic cardiovascular disease (ASCVD) grade assessment were performed on MS patients. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of MS patients before and after transplantation. A total of 237 patients were included, including 42 in the MS group and 195 in the non-MS group. For MS patients, WMT significantly improved the comprehensive efficacy of MS in short term 40.48% (p<0.001), medium term 36.00% (p=0.003), and long term 46.15% (p=0.020). Short-term significantly reduced FBG (p=0.023), TG (p=0.030), SBP (p=0.026) and BMI (p=0.031), and increased HDL-c (p=0.036). The medium term had a significant reduction in FBG (p=0.048), TC (p=0.022), LDL-c (p=0.043), non-HDL-c (p=0.024) and BMI (p=0.048). WMT had a significant short term (p=0.029) and medium term (p=0.011) ASCVD downgrading effect in the high-risk group of MS patients. WMT improved gut microbiota in MS patients. WMT had a significant improvement effect on MS patients and a significant downgrade effect on ASCVD risk in the high-risk group of patients with MS. WMT could restore gut microbiota homeostasis in MS patients. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of MS.

Metataxonomic and Metabolic Impact of Fecal Microbiota Transplantation From Patients With Pancreatic Cancer Into Germ-Free Mice: A Pilot Study.

BackgroundBody weight (BW) loss is prevalent in patients with pancreatic cancer (PC). Gut microbiota affects BW and is known to directly shape the host immune responses and antitumor immunity. This pilot study evaluated the link between gut microbiota, metabolic parameters and inflammatory/immune parameters, through the fecal material transplantation (FMT) of PC patients and healthy volunteers into germ-free (GF) mice.MethodsWe transplanted the feces from five PC patients and five age- and gender-matched healthy volunteers into two GF mice each. Mouse BW and energy intake were measured every 1-5 days, oral glucose on day 21, insulin tolerance on day 26, fecal bacterial taxonomic profile by 16S rRNA gene sequencing on day 5, 10, 15 and 30, and gut-associated lymphoid tissue T cells, plasma cytokines and weights of fat and muscle mass at sacrifice (day 34). Results are presented as mean ± SD. The continuous parameters of mice groups were compared by linear univariate regressions, and their bacterial communities by Principal Coordinates Analysis (PCoA), Bray-Curtis similarity and ANCOM test.ResultsRecipients of feces from PC patients and healthy volunteers had similar BW gain and food intake. Visceral fat was lower in recipients of feces from PC patients than from healthy individuals (0.72 ± 0.17 vs. 0.92 ± 0.14 g; coeff -0.19, 95% CI -0.38, -0.02, p=0.035). The other non-metataxonomic parameters did not differ between groups. In PCoA, microbiota from PC patients clustered apart from those of healthy volunteers and the same pattern was observed in transplanted mice. The proportions of Clostridium bolteae, Clostridium scindens, Clostridium_g24_unclassified and Phascolarctobacterium faecium were higher, while those of Alistipes obesi, Lachnospiraceae PAC000196_s and Coriobacteriaceae_unclassified species were lower in PC patients and in mice transplanted with the feces from these patients.ConclusionIn this pilot study, FMT from PC patients was associated with a decrease in visceral fat as compared to FMT from healthy individuals. Some of the differences in fecal microbiota between PC and control samples are common to humans and mice. Further research is required to confirm that feces contain elements involved in metabolic and immune alterations.

Impact of fecal microbiota transplantation with capsules on the prevention of metabolic syndrome among patients with obesity.

Fecal microbiota transplantation (FMT) has been studied for the treatment of metabolic syndrome with varying success. However, the possibility of utilizing FMT to prevent metabolic syndrome is to date unknown. Secondary analysis of a previously published double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients was conducted. Post-prandial glucose and insulin levels were measured (NCT02741518). A total of 22 patients were enrolled, 11 in each arm. There were no baseline differences in the area under the curve (AUC) of glucose or insulin in the FMT group compared to placebo. There was a significant change in glucose AUC at week 12 compared to baseline, and in the insulin AUC at week 6 compared to baseline in the FMT group vs. placebo (change in glucose AUC (mg/dl × 60min): 579 vs 1978, p = 0.03) (change in insulin AUC (μU/ml × 60min): 137 vs 2728, p = 0.01). These data suggest that FMT may have a potential role in preventing the development of metabolic syndrome in patients with obesity.

The Role of Gut Microbiome-Targeted Therapy in Nonalcoholic Fatty Liver Disease

To review the role and progress of microbiome-targeting therapies in nonalcoholic fatty liver disease (NAFLD). This review summarizes recent clinical trials of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) and analyzes the potential clinical impact of reverse dysbiosis in NAFLD. Though results might be mixed, the recent randomized clinical trials and systemic reviews indicate probiotics, prebiotics, and synbiotics are promising therapies that improve transaminitis and hepatic steatosis. The scarcity of FMT clinical trials limits the power to conclude the direct impact of FMT on NAFLD. Given the rapidly growing prevalence of NAFLD and the lack of effective pharmacological intervention, there is an urgent need for the development of novel therapeutic strategies. Despite the advancements in and promising results of gut microbiome (GM) restoring remedies, further studies are needed to assess their beneficial efficacy, safety, and sustainability to develop novel pharmacologic approaches to NAFLD.

Impact of fecal microbiota transplantation on chronic recurrent pouchitis in ulcerative colitis with ileo-anal anastomosis: study protocol for a prospective, multicenter, double-blind, randomized, controlled trial

BackgroundAlmost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch–anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available.Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis.MethodsOur project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation.DiscussionOn April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future.Trial registrationClinicalTrials.gov, NCT03524352. Registered on 14 May 2018.

Fecal microbiota transplantation for patients on antibiotic treatment with C. difficile infection history (GRAFT): Study protocol for a phase II, randomized, double-blind, placebo-controlled trial to prevent recurrent C. difficile infections

Recurrent Clostridiodes difficile infections (rCDIs) are a burdensome problem. Patients with a history of CDI that are prescribed antibiotics are at a high risk for recurrence. Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for rCDI, though there is little information on the impact of FMT with antibiotics on the gut microbiome. We are conducting a clinical trial of FMT to prevent rCDI in patients with a history of CDI currently taking antibiotics. Our primary objective is to determine the effect of FMT on the gut microbiome during antibiotic exposure. Our secondary aim is to assess safety and feasibility of using FMT as a prophylaxis for CDI. We plan to enroll 30 patients into a phase II randomized, double-blind, placebo-controlled trial with three arms: (1) 5 FMT capsules per day during antibiotic treatment and for 7 days post antibiotic cessation, (2) a one-time dose of 30 FMT capsules 48–72 h post cessation of antibiotic treatment, or (3) 5 placebo capsules per day during antibiotic treatment and for 7 days post antibiotic treatment. Patients provide stool samples throughout the duration of the study and are cultured C. difficile. Sequencing of the V4 region of the 16S rRNA gene will be carried out to assess the gut microbiota. Results of this study will provide information on the impact of FMT on the gut microbiome as well as the necessary data to examine whether or not prophylactic FMT should be explored further as a way to prevent CDI recurrence.

OR26-06 Fecal Microbiota Transplantation Trial for the Improvement of Metabolism (FMT-TRIM): A Randomized Double-Blind Placebo-Controlled Pilot Trial

Background: There is intense interest about the therapeutic potential of altering gut microbiota to improve metabolism, based primarily on intriguing animal studies. One prior trial of fecal microbiota transplantation (FMT) in obese men found that improved metabolic response after FMT was predicted by low baseline microbiome diversity. In the current trial, we investigated the safety and efficacy of weekly oral FMT capsules to improve glycemic outcomes in obese adults, and also explored determinants of successful microbiome engraftment and metabolic improvement after FMT. Methods: FMT-TRIM was a double-blind randomized placebo-controlled pilot trial of weekly oral FMT vs placebo capsules for 6 weeks in 24 obese adults with mild-moderate insulin resistance. Each participant in the FMT arm received capsules derived from one of 4 metabolically healthy lean donors (BMI 18.5-23 kg/m2). The primary outcome was change in insulin sensitivity assessed by hyperinsulinemic euglycemic clamp at 0 and 6 weeks. Secondary outcomes included body weight, metabolic labs, and body composition assessed by DXA over 12 weeks. 16SV4 rRNA sequencing was performed to assess microbiome composition and engraftment. Post-hoc exploratory analyses investigated metabolic outcomes after stratification by baseline microbiome diversity. Results: FMT and placebo groups were well balanced in terms of age (mean±SD 40±9 yrs), BMI (40±6 kg/m2), sex (72% female), and baseline metabolic measures. During the study, there were no statistically significant differences in insulin sensitivity between the FMT and placebo groups (+5 ± 12% FMT vs -3 ± 32% placebo, mean percent difference 9%, 95% CI -5% to 28%; p=0.16). There was a minor improvement in HbA1c at 12 weeks after FMT as compared to placebo (mean difference -0.1, 95% CI -0.3-0.01), but no significant differences in other metabolic labs, body weight, or body composition. Microbial engraftment varied by donor but was present in most FMT recipients, with persistence of engrafting strains throughout the 12-week study. Subgroup analyses of subjects with low microbiome diversity at baseline (FMT n=4, placebo n=7) showed a relative benefit of FMT over placebo at 12 weeks for HbA1c (mean difference -0.2, 95% CI -0.4 to -0.01), total cholesterol (-22 mg/dL, 95% CI -40 to -4 mg/dL), and fasting glucose (-10 mg/dL, 95% CI -19 to -1 mg/dL). There were no significant differences in adverse events between FMT and placebo groups. Conclusion: Weekly administration of FMT capsules results in gut microbiota engraftment for at least 12 weeks but does not meaningfully alter human metabolism in an unselected population of obese adults. Future studies are needed to elucidate the role of baseline recipient microbial diversity and other factors on the impact of FMT.

Impact of fecal microbiota transplantation on TGF-β1/Smads/ERK signaling pathway of endotoxic acute lung injury in rats.

Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Studies have shown that intestinal microbiota affect the pathology and immune function of respiratory diseases through the "gut-lung axis". The authors investigated the therapeutic effect of fecal microbiota transplantation (FMT) in rats with ALI induced by lipopolysaccharide (LPS). Rats were treated with FMT, and then measured lung wet/dry ratio, PaO2 in artery, proinflammatory marker, and TGF-β1, Smad3, Smad7, and phosphorylated ERK (p-ERK) protein levels, as well as a histopathologic analysis and high-throughput sequencing of intestinal microbiota. FMT significantly reduced lung wet/dry ratio and TNF-α, IL-1β, and IL-6 levels, but increased the levels of PaO2 in artery. In addition, FMT significantly decreased the expression of TGF-β1, Smad3, and p-ERK, while increased the levels of Smad7. Lung histopathological analyses showed that FMT reduced the inflammatory cell infiltration and interstitial lung exudates. High-throughput sequencing of intestinal microbiota analyses showed that FMT reconstructed the structure of intestinal microbiota, and increased the gene abundance of the bacterial community. Therefore, FMT may act on the TGF-β1/Smads/ERK pathway by regulating intestinal microbiota, inhibiting immune inflammation, reducing the production of inflammatory markers in the body and release, and reducing alveolar epithelial damage and repair, thereby improving the endotoxic ALI in rats induced by LPS.

Fecal microbiota transplantation in children: current concepts.

Administration of fecal material into the gastrointestinal tract, termed fecal microbiota transplantation (FMT), is increasingly recognized as an effective treatment option for recurrent Clostridium difficile infection (RCDI). The impact of FMT on host microbial communities and subsequent disease states has also been explored in recent years for conditions as varied as inflammatory bowel disease especially ulcerative colitis, metabolic diseases, such as diabetes, graft-versus-host disease in hematopoietic stem cell transplant recipients, and autism and autism spectrum disorders. The purpose of this article is to review the evidence for FMT as a treatment option in various pediatric illnesses. The rate of C. difficile infection is rising among children, and is associated with significant morbidity and disease, with recurrence in up to 20% of pediatric patients. Several randomized controlled trials evaluating the utility of FMT in RCDI in comparison to vancomycin have been published and demonstrate high rates of efficacy between 70 and 100%. In addition, the safety of FMT in the treatment of RCDI has been well described in the adult population, with several pediatric case series demonstrating similar rates of tolerability and adverse events. FMT in ulcerative colitis appears promising, especially with multiple infusions administered via the lower gastrointestinal tract. However, there are several limitations, including the lack of uniformity of protocols used, source of FMT, route of administration and the lack of standardization of concomitant therapies. The data on usage of FMT for other indications are preliminary and limited. FMT is recognized as an effective treatment option for RCDI and is increasing sought by parents. Although limited, pediatric studies to date on the use of FMT for RCDI demonstrate similar efficacy rates as in the adult population. FMT has been proposed as a treatment option for an increasing number of pediatric conditions, and additional studies are needed to delineate the efficacy of FMT outside of RCDI, as well as its short and long-term impacts on human health.

Impact of Fecal Microbiota Transplantation on Obesity and Metabolic Syndrome—A Systematic Review

Fecal microbiota transplantation (FMT) is a gut microbial-modulation strategy that has been investigated for the treatment of a variety of human diseases, including obesity-associated metabolic disorders. This study appraises current literature and provides an overview of the effectiveness and limitations of FMT as a potential therapeutic strategy for obesity and metabolic syndrome (MS). Five electronic databases and two gray literature sources were searched up to 10 December 2018. All interventional and observational studies that contained information on the relevant population (adult patients with obesity and MS), intervention (receiving allogeneic FMT) and outcomes (metabolic parameters) were eligible. From 1096 unique citations, three randomized placebo-controlled studies (76 patients with obesity and MS, body mass index = 34.8 ± 4.1 kg/m2, fasting plasma glucose = 5.8 ± 0.7 mmol/L) were included for review. Studies reported mixed results with regards to improvement in metabolic parameters. Two studies reported improved peripheral insulin sensitivity (rate of glucose disappearance, RD) at 6 weeks in patients receiving donor FMT versus patients receiving the placebo control. In addition, one study observed lower HbA1c levels in FMT patients at 6 weeks. No differences in fasting plasma glucose, hepatic insulin sensitivity, body mass index (BMI), or cholesterol markers were observed between two groups across all included studies. While promising, the influence of FMT on long-term clinical endpoints needs to be further explored. Future studies are also required to better understand the mechanisms through which changes in gut microbial ecology and engraftment of microbiota affect metabolic outcomes for patients with obesity and MS. In addition, further research is needed to better define the optimal fecal microbial preparation, dosing, and method of delivery.

Fecal Microbiota Transplantation for the Treatment of Clostridium difficile Infection

By systematic review, we assessed the impact of fecal microbiota transplantation (FMT) for the treatment of Clostridium difficile (CD)-associated diarrhea. Fecal microbiota microbiota transplantation from a healthy donor into an individual with CD infection (CDI) can resolve symptoms. We conducted systematic searches in PubMed, SCOPUS, Web of Science, and Cochrane Library. The last search was run on February 8, 2013. The following Medical Subject Headings terms and keywords were used alone or in combination: Clostridium difficile; Clostridium infection; pseudomembranous colitis; feces; stools; fecal suspension; fecal transplantation; fecal transfer; fecal infusion; microbiota; bacteriotherapy; enema; nasogastric tube; colonoscopy; gastroscopy; fecal donation; donor. A critical appraisal of the clinical research evidence on the effectiveness and safety of FMT for the treatment of patients with CD-associated diarrhea was made. Twenty full-text case series, 15 case reports, and 1 randomized controlled study were included for the final analysis. Almost all patients treated with donors' fecal infusion experienced recurrent episodes of CD-associated diarrhea despite standard antibiotic treatment. Of a total of 536 patients treated, 467 (87%) experienced resolution of diarrhea. Diarrhea resolution rates varied according to the site of infusion: 81% in the stomach; 86% in the duodenum/jejunum; 93% in the cecum/ascending colon; and 84% in the distal colon. No severe adverse events were reported with the procedure. FMT seems efficacious and safe for the treatment of recurrent CDI. Hospitals should encourage the development of fecal transplantation programs to improve therapy of local patients.

Fecal microbiota transplantation: effectiveness, complexities, and lingering concerns.

The mammalian colon is home to a microbial ecosystem that enhances resistance to infection, stimulates mucosal immune defenses, synthesizes essential vitamins, and promotes caloric uptake by hydrolyzing complex carbohydrates. The bacterial populations inhabiting the gut are complex and vary between different individuals. Clinical and experimental studies reveal that the colonic microbiota can enhance or ameliorate intestinal and systemic inflammatory diseases. Because of its potential to enhance resistance to infection and to reduce inflammatory diseases, targeted manipulation of microbial populations is a growing focus of investigation. The most dramatic manipulation of the intestinal microbiota involves fecal microbiota transplantation (FMT) from healthy donors to individuals with specific diseases. Remarkable clinical effectiveness of FMT has been demonstrated for recurrent Clostridium difficile infection and ongoing studies are investigating FMT for other diseases. Transplantation of complex microbial populations to recipients likely triggers mucosal immune responses that, depending on the microbiota composition and the recipient's genotype, could range from pro- to anti-inflammatory. The impact of FMT on the recipient immune system is complex and unpredictable. Ongoing discovery of commensal microbes and investigations of their impact on the host will lead to the development of new probiotic agents and microbial consortia that will eventually replace FMT.