Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose

Allegretti, Jessica R.; Fischer, Monika; Sagi, S V; Bohm, Matthew; Fadda, Hala M.; Ranmal, Sejal R.; Budree, Shrish; Basit, Abdul W.; Glettig, Dean L.; Serna, Eva L. de la; Gentile, Amanda; Gerardin, Ylaine; Timberlake, Sonia; Sadovsky, Rotem Gura; Smith, Mark; Kassam, Zain

doi:10.1007/s10620-018-5396-6

Cited by 55 publications

(47 citation statements)

References 22 publications

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“…A key advantage of a pooled stool is that it increases the chances of transmitting key bacteria to the recipient; however, it is not clear whether this hypothesis is translated into real efficacy (41,42).…”

Section: Discussionmentioning

confidence: 99%

Fecal microbiota transplantation ameliorates active ulcerative colitis

Chen

Huang

et al. 2020

Exp Ther Med

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Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.

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Section: Discussionmentioning

confidence: 99%

Fecal microbiota transplantation ameliorates active ulcerative colitis

Chen

Huang

et al. 2020

Exp Ther Med

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“…The viabilities of approximately 90% were retained after these capsules were exposed to gastric environment for 2 h while the unencapsulated probiotics showed poor tolerance to the gastric environment [83]. Based on a comparative cohort analysis in patients, Allegretti et al [84] also demonstrated the effective colon-targeting of the fecal microbiota transplantation capsules coated with a blend of enzyme-triggered and pH-responsive polymers.…”

Section: Polysaccharide-based Systemsmentioning

confidence: 99%

Strategic Approaches for Colon Targeted Drug Delivery: An Overview of Recent Advancements

et al. 2020

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Colon targeted drug delivery systems have gained a great deal of attention as potential carriers for the local treatment of colonic diseases with reduced systemic side effects and also for the enhanced oral delivery of various therapeutics vulnerable to acidic and enzymatic degradation in the upper gastrointestinal tract. In recent years, the global pharmaceutical market for biologics has grown, and increasing demand for a more patient-friendly drug administration system highlights the importance of colonic drug delivery as a noninvasive delivery approach for macromolecules. Colon-targeted drug delivery systems for macromolecules can provide therapeutic benefits including better patient compliance (because they are pain-free and can be self-administered) and lower costs. Therefore, to achieve more efficient colonic drug delivery for local or systemic drug effects, various strategies have been explored including pH-dependent systems, enzyme-triggered systems, receptor-mediated systems, and magnetically-driven systems. In this review, recent advancements in various approaches for designing colon targeted drug delivery systems and their pharmaceutical applications are covered with a particular emphasis on formulation technologies.

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“…The oral capsule proved almost as e cient as enema forms (− 3.8 dysbiotic days), even if the amount of administered bacteria was 100 times lower and required a longer administration period (1 week compared to two days). In previous studies, two approaches were mainly developed for FMT oral capsules, rst freezing at -80 °C with glycerol, then more recently freeze-drying with various cryoprotectants, as performed in the present study [41][42][43]. Interestingly, Jiang and colleagues (2017) [42] showed in mice that there was no difference in e ciency of frozen and lyophilized capsules in rCDI treatment, and that products can be stored up to 7 months without losing microbiota composition and therapeutic e cacy.…”

Section: Discussionmentioning

confidence: 82%

“…The effect of these two formulations was compared to that of a new caecumreleasing capsule containing a freeze-dried form of the enema formulation. Oral capsule is the most recently developed mode of stool delivery, the rst formulation being described in 2014 [40,41]. Capsules which are esthetically pleasing, convenient and minimally invasive are preferred by patients, and present the bene t to be the cheapest FMT mode of administration [18,40,41].…”

Section: Discussionmentioning

confidence: 99%

“…Oral capsule is the most recently developed mode of stool delivery, the rst formulation being described in 2014 [40,41]. Capsules which are esthetically pleasing, convenient and minimally invasive are preferred by patients, and present the bene t to be the cheapest FMT mode of administration [18,40,41]. Enemas were directly introduced into the ARCOL model since in humans they are delivered to the distal colon using a canula.…”

Section: Discussionmentioning

confidence: 99%

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An oral FMT capsule as efficient as an enema for microbiota reconstruction following disruption by antibiotics, as assessed in an in vitro human gut model.

Verdier

Denis

Cyrielle³

et al. 2020

Preprint

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Abstract Background Fecal microbiota transfer (FMT) is an innovative treatment already successfully used in recurrent Clostridioides difficile infections. Researchers and clinicians are exploring its potential for treating other digestive or extra-intestinal pathologies where gut microbial dysbiosis has been evidenced, such as inflammatory bowel disease, obesity or cancers. Oral capsules were recently developed to address gaps of traditional routes of FMT such as enema or colonoscopy. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics and cost constraints. The aim of the study was to use the in vitro human Artificial Colon ARCOL to compare the efficiency of two enema dosage (10 and 30 g) and a new oral caecum-release capsule in restoring gut microbiota composition and activity after treatment with ciprofloxacin, an antibiotic used in leukemia patients. Results By integrating the main physicochemical parameters of the human colon (pH, retention time, nutrient supply and anaerobiosis), ARCOL was shown to capture microbial diversity and inter-individual variability of stools from three healthy donors. Treatment with ciprofloxacin led to a state of marked dysbiosis with a sharp decrease in fermentation activities (production of gases and short chain fatty acids), a loss of microbial diversity and a shift in bacterial populations. All FMT treatments were able to speed-up the restoration of microbial profiles and functions, by decreasing the number of dysbiotic days from 12 to 7–8 depending on the FMT modes. Of note, the bacterial load showed no major influence on enema performance, and oral capsule was almost as efficient as enema even if the amount of administered bacteria was 100 times lower. Conclusions This study provides the first example of using an in vitro human colon model for evaluating autologous FMT efficiency and highlights the potential of oral capsule compared to a traditional enema formulation. This new mode of FMT administration combines efficiency with convenient and minimally invasive mode of administration. In accordance to 3R rules, gut models like ARCOL can be advantageously used to test FMT in preclinical phases as an alternative to in vivo assays.

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Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose

Cited by 55 publications

References 22 publications

Fecal microbiota transplantation ameliorates active ulcerative colitis

Fecal microbiota transplantation ameliorates active ulcerative colitis

Strategic Approaches for Colon Targeted Drug Delivery: An Overview of Recent Advancements

An oral FMT capsule as efficient as an enema for microbiota reconstruction following disruption by antibiotics, as assessed in an in vitro human gut model.

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