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.

Abstract

<jats:title>Abstract</jats:title> <jats:p>Background Fecal microbiota transfer (FMT) is an innovative treatment already successfully used in recurrent <jats:italic>Clostridioides difficile</jats:italic> 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 <jats:italic>in vitro</jats:italic> 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 <jats:italic>in vitro</jats:italic> 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 <jats:italic>in vivo</jats:italic> assays.</jats:p>