Abstract
Fecal microbiota transplantation (FMT) is an innovative therapy already used in humans to treat Clostridioides difficile infections associated with massive use of antibiotics. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics, and cost constraints. In the present study, an in vitro model of the human colon reproducing medically relevant perturbation of the colonic ecosystem by antibiotherapy was used to compare the efficiency of traditional FMT enema formulations and a new oral capsule in restoring gut microbiota composition and activity. Loss of microbial diversity, shift in bacterial populations, and sharp decrease in fermentation activities induced in vivo by antibiotherapy were efficiently reproduced in the in vitro model, while capturing inter-individual variability of gut microbiome. Oral capsule was as efficient as enema to decrease the number of disturbed days and bacterial load had no effect on enema performance. This study shows the relevance of human colon models as an alternative approach to in vivo assays during preclinical studies for evaluating FMT efficiency. The potential of this in vitro approach could be extended to FMT testing in the management of many digestive or extra-intestinal pathologies where gut microbial dysbiosis has been evidenced such as inflammatory bowel diseases, obesity or cancers.
Highlights
The digestive tract harbors the largest and most complex microbial community of the human body, namely the gut microbiota, which is mainly composed of thousands of bacterial species and members of Archaea, Eukaryotes, and viruses [1,2,3]
fecal microbiota transplantation (FMT) treatments led to an earlier restart of NaOH consumption compared to ATB control, two days before for 30 g and 10 g enema and only one day before for oral capsule
We described for the first time the use of a dynamic computer-controlled applied: ciprofloxacin (ATB control, blue), ciprofloxacin and 30 g enema, ciprofin vitro model of the human colon, namely ARtificial COLon (ARCOL), as an alternative to in vivo assays in loxacin and 10 g enema, and ciprofloxacin with oral capsules
Summary
The digestive tract harbors the largest and most complex microbial community of the human body, namely the gut microbiota, which is mainly composed of thousands of bacterial species and members of Archaea, Eukaryotes, and viruses [1,2,3]. A large number of studies in animal models and humans have shown that a persistent imbalance in gut microbial community is associated with intestinal disorders such as inflammatory bowel diseases or irritable bowel syndrome or even extra-digestive pathologies like diabetes, obesity, cancers or neurological disorders. This alteration, named dysbiosis, has been associated with loss of richness and diversity, loss of keystone taxa, shift in metabolic pathways and/or bloom of pathobionts like Enterobacteriaceae or Clostridiaceae [4,5].
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