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The fecal microbiome is identical to the gut microbial communities and provides an easy access to the gut microbiome. Therefore, fecal microbial transplantation (FMT) strategies have been used to alter dysbiotic gut microbiomes with healthy fecal microbiota, successfully alleviating various metabolic disorders, such as obesity, type 2 diabetes, and inflammatory bowel disease (IBD). However, the success of FMT treatment is donor-dependent and variations in gut microbes cannot be avoided. This problem may be overcome by using a cultured fecal microbiome. In this study, a human fecal microbiome was cultured using five different media; growth in brain heart infusion (BHI) media resulted in the highest microbial community cell count. The microbiome (16S rRNA) data demonstrated that the cultured microbial communities were similar to that of the original fecal sample. Therefore, the BHI-cultured fecal microbiome was selected for cultured FMT (cFMT). Furthermore, a dextran sodium sulfate (DSS)-induced mice-IBD model was used to confirm the impact of cFMT. Results showed that cFMT effectively alleviated IBD-associated symptoms, including improved gut permeability, restoration of the inflamed gut epithelium, decreased expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6, IL-12, and IL-17), and increased expression of anti-inflammatory cytokines (IL-4 and IL-10). Thus, study's findings suggest that cFMT can be a potential alternative to nFMT. KEY POINTS: • In vitro fecal microbial communities were grown in a batch culture using five different media. • Fecal microbial transplantation was performed on DSS-treated mice using cultured and normal fecal microbes. • Cultured fecal microbes effectively alleviated IBD-associated symptoms.

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In the human body, eukaryotic somatic cells and prokaryotic microorganisms live together. In this state, the body can be viewed as a "superorganism." Symbiotic life with commensal microorganisms can be observed in almost every part of the body. Intestinal microbiota plays an important role in health and disease, and in shaping and regulating neuronal functions from the intrauterine period to the end of life. Microbiota-based treatment opportunities are becoming more evident in both understanding the etiopathogenesis and treatment of neuropsychiatric disorders, especially depression. Antidepressant drugs, which are the first choice in the treatment of depression, also have antimicrobial and immunomodulatory mechanisms of action. From these perspectives, direct probiotics and fecal microbiota transplantation are treatment options to modulate microbiota composition. There are few preclinical and clinical studies on the effectiveness and safety of these applications in depression. The information obtained from these studies may still be at a doxa level. However, the probability that this information will become episteme in the future seems to be increasing.

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Pouchitis, as the most common complication after ileal pouch-anal anastomosis (IPAA), has an incidence from 7% to 46%. Pouchitis treatment still represents one of the biggest gaps of knowledge in the treatment of diseases. This review has focused on achievements and challenges in the treatment of pouchitis. A combined assessment of symptoms, endoscopic findings, histologic results, quick biomarkers, and fecal calprotectin test were determined to be valuable diagnostic criteria. Conventional therapy was described as a modification of bacterial flora, mainly with antibiotics and more recently with probiotics such as bifidobacteria, lactobacilli, and streptococci. Other therapeutic approaches such as anti-tumor necrosis factor, infliximab, adalimumab, vedolizumab, ustekinumab, tacrolimus, tofacitinib, thiopurines, corticosteroids, prolyl hydroxylase-containing enzymes, povidone-iodine, dextrose spray, fecal microbiota transplantation, herbal medicines, and leukocyte apheresis have been discussed. Changes in dietary components, and administration of complementary and alternative medicine, probiotics, and fecal transplantation in addition to conventional therapies were also shown to affect the outcome of disease. Due to the potential significant impairment in quality of life caused by pouchitis, it is essential to address the gaps in knowledge for both patients and physicians in its treatment. Therefore, well-designed and adequately powered studies should assess the optimal treatment for pouchitis.

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Fecal filtrate transfer (FFT) is emerging as a safer alternative to traditional fecal microbiota transplantation (FMT) - particularly in the context of necrotizing enterocolitis (NEC), a severe gastrointestinal condition affecting preterm infants. Using a preterm piglet model, FFT has demonstrated superiority over FMT in safety and NEC prevention. Since FFT is virtually devoid of bacteria, prokaryotic viruses (bacteriophages) are assumed to mediate the beneficial effects. However, this assumption remains unproven. To address this gap, we separated virus-like particles (30 kDa to 0.45 µm) of donor feces from the residual postbiotic fluid. We then compared clinical and gut microbiota responses to these fractions with the parent FFT solution after transferring them to NEC-susceptible preterm piglets. Virome transfer was equally effective as FFT in reducing the severity of NEC-like pathology. The bacterial compositional data corroborated clinical findings as virome transfer reduced the relative abundance of several NEC-associated pathogens e.g. Klebsiella pneumoniae and Clostridium perfringens. Virome transfer diversified gut viral communities with concomitant constraining effects on the bacterial composition. Unexpectedly, virome transfer, but not residual postbiotic fluid, led to earlier diarrhea. While diarrhea may be a minor concern in human infants, future work should identify ways of eliminating this side effect without losing treatment efficacy.

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Imbalanced microbiota may contribute to the pathophysiology of irritable bowel syndrome (IBS), thus fecal microbiota transplantation (FMT) has been suggested as a potential treatment. Previous studies on the relationship between clinical improvement and microbiota after FMT have been inconclusive. In this study, we used 16S rRNA gene amplicon and shotgun metagenomics data from a randomized, placebo controlled FMT trial on 49 IBS patients to analyze changes after FMT in microbiota composition and its functional potential, and to identify connections between microbiota and patients' clinical outcome. As a result, we found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of symptoms in IBS patients. Notably, a donor derived strain of Prevotella copri dominated the microbiota in those patients in the FMT group who had a low relative abundance of P. copri pre-FMT. The results highlight the multifactorial nature of IBS and the role of recipient's microbiota in the colonization of donor's strains.

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Recent research indicates that the microbiome has a significant impact on the progression of inflammatory bowel disease (IBD) and that creating therapies that change its composition could positively impact the outcomes of IBD treatment. This review summarizes the results of extensive studies that examined IBD patients undergoing several therapies, including anti-TNF medication, vedolizumab, ustekinumab, probiotics, and fecal microbiota transplantation (FMT), and the alterations in their gut microbiota's composition and function. The objective was to investigate the variety and effectiveness of microbial species in order to discover new biomarkers or therapeutic targets that could improve the outcome of treatment for these patients. This research aimed to offer useful insights into personalized medicine techniques for managing IBD. Beneficial bacteria such as Faecalibacterium prausnitzii and Roseburia have been consistently linked to favorable clinical outcomes, whereas pathogenic bacteria such as Escherichia coli and Clostridioides difficile are associated with worsening disease conditions. Although many studies have examined the role of gut microbiota in IBD, there is still a need for more targeted research on the connection between specific microbial communities and treatment outcomes. This study sought to address this gap by exploring the intricate relationship between the gut microbiota composition and the effectiveness of IBD medications.

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Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.

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Fecal microbial transplantation (FMT) for inflammatory diseases or refractory immune checkpoint inhibitor therapy is less effective than for preventing recurrent Clostridioides difficile infection. This commentary outlines strategies to use biomarkers of successful FMT to guide newer approaches to restore microbial homeostasis in individuals with dysbiosis-mediated inflammation.

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Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. Here, we compared behavior profiles of control, germ-free (GF), and antibiotic-treated mice, as well as re-colonized GF mice to understand the impact of the gut microbiome on aggression using the resident-intruder paradigm. Our findings revealed a link between gut microbiome depletion and higher aggression, accompanied by notable changes in urine metabolite profiles and brain gene expression. This study extends beyond classical murine models to humanized mice to reveal the clinical relevance of early-life antibiotic use on aggression. Fecal microbiome transplant from infants exposed to antibiotics in early life (and sampled one month later) into mice led to increased aggression compared to mice receiving transplants from unexposed infants. This study sheds light on the role of the gut microbiome in modulating aggression and highlights its potential avenues of action, offering insights for development of therapeutic strategies for aggression-related disorders.

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Fecal microbiota transplants (FMTs) recently entered the cancer therapeutics field as a method to resensitize treatment-resistant melanoma patients to immune checkpoint inhibitors (ICIs). In this issue of Cell Host & Microbe, Kim and colleagues extend its utility to other solid tumors, including esophageal and hepatocellular carcinomas.1.

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The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment.

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BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.

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Importance: Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models. Objective: To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT. Design, Setting, and Participants: This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn & Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis. Intervention: Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy. Main Outcomes and Measures: The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs). Results: The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P = .75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P = .003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group. Conclusions and Relevance: FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD. Trial Registration: ClinicalTrials.gov Identifier: NCT04854291.

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BACKGROUND: Fecal microbiota transplantation (FMT) is a therapeutic intervention used to treat diseases associated with the gut microbiome. In the human gut microbiome, phages have been implicated in influencing human health, with successful engraftment of donor phages correlated with FMT treatment efficacy. The impact that gastrointestinal phages exert on human health has primarily been connected to their ability to modulate the bacterial communities in the gut. Nonetheless, how FMT affects recipients' phage populations, and in turn, how this influences the gut environment, is not yet fully understood. In this study, we investigated the effects of FMT on the phageome composition of participants within the Gut Bugs Trial (GBT), a double-blind, randomized, placebo-controlled trial that investigated the efficacy of FMT in treating obesity and comorbidities in adolescents. Stool samples collected from donors at the time of treatment and recipients at four time points (i.e., baseline and 6 weeks, 12 weeks, and 26 weeks post-intervention), underwent shotgun metagenomic sequencing. Phage sequences were identified and characterized in silico to examine evidence of phage engraftment and to assess the extent of FMT-induced alterations in the recipients' phageome composition. RESULTS: Donor phages engrafted stably in recipients following FMT, composing a significant proportion of their phageome for the entire course of the study (33.8 ± 1.2% in females and 33.9 ± 3.7% in males). Phage engraftment varied between donors and donor engraftment efficacy was positively correlated with their phageome alpha diversity. FMT caused a shift in recipients' phageome toward the donors' composition and increased phageome alpha diversity and variability over time. CONCLUSIONS: FMT significantly altered recipients' phage and, overall, microbial populations. The increase in microbial diversity and variability is consistent with a shift in microbial population dynamics. This proposes that phages play a critical role in modulating the gut environment and suggests novel approaches to understanding the efficacy of FMT in altering the recipient's microbiome. TRIAL REGISTRATION: The Gut Bugs Trial was registered with the Australian New Zealand Clinical Trials Registry (ACTR N12615001351505). Trial protocol: the trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.

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BACKGROUND: Fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases. METHODS: To overcome these challenges, we developed methods to broaden FVT's clinical application while maintaining efficacy and increasing safety. Specifically, we employed the following approaches: (1) chemostat-fermentation to reproduce the bacteriophage FVT donor component and remove eukaryotic viruses (FVT-ChP), (2) solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT), and (3) pyronin-Y treatment to inhibit RNA virus replication (FVT-PyT). We assessed the efficacy of these processed FVTs in a C. difficile infection mouse model and compared them with untreated FVT (FVT-UnT), FMT, and saline. RESULTS: FVT-SDT, FVT-UnT, and FVT-ChP reduced the incidence of mice reaching the humane endpoint (0/8, 2/7, and 3/8, respectively) compared to FMT, FVT-PyT, and saline (5/8, 7/8, and 5/7, respectively) and significantly reduced the load of colonizing C. difficile cells and associated toxin A/B levels. There was a potential elimination of C. difficile colonization, with seven out of eight mice treated with FVT-SDT testing negative with qPCR. In contrast, all other treatments exhibited the continued presence of C. difficile. Moreover, the results were supported by changes in the gut microbiome profiles, cecal cytokine levels, and histopathological findings. Assessment of viral engraftment following FMT/FVT treatment and host-phage correlations analysis suggested that transfer of phages likely were an important contributing factor associated with treatment efficacy. CONCLUSIONS: This proof-of-concept study shows that specific modifications of FVT hold promise in addressing challenges related to donor variability and infection risks. Two strategies lead to treatments significantly limiting C. difficile colonization in mice, with solvent/detergent treatment and chemostat propagation of donor phages emerging as promising approaches. Video Abstract.

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Introduction: Clostridioides difficile infections (CDI) continue to pose a challenge for clinicians. Fecal microbiota transplantation (FMT) is an effective treatment option in CDI. Furthermore, recent and ongoing studies suggest potential benefits of FMT in other diseases as well. Methods: We would like to present a novel protocol for encapsulation of lyophilized fecal material. Our method provides with better compliance as well as improved flexibility, storage and safety. Results: FMT was conducted in 28 patients with an overall success rate of 82,14% using apsules containing lyophilized stool. 16 of patients were given capsules with lessened bacteria counts. The success rate in this group was 93,75%. Discussion: The results highlight the still unanswered questions about the mechanism of action and contribute to a wider use of FMT in the clinical praxis and in research.

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The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.

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Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.

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Food and Drug Administration approval of the first microbiome therapies represents a true expansion the treatment paradigm for Clostridioides difficile but raises new questions about the future role of fecal microbiota transplantation. The authors outline the advances in microbiome therapeutic development that have addressed fecal microbiota transplantation's (FMT's) inherent limitations of safety and scalability. The authors also suggest that as microbiome therapeutic development continues for other indications, FMT will likely remain a necessary model of human microbiota dynamics for translational research.

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