Efficacious outcome employing fecal bacteriotherapy in severe Crohn’s colitis complicated by refractory Clostridium difficile infection

Excerpt

Human intestinal microbiomes (mutualistic, commensal intestinal fecal flora and its genomic composition) [1] are complex ecosystems which serve protective, trophic, and metabolic functions influencing immune regulation, colonization resistance (preventing pathogenic microorganism colonization), and the production of essential short-chain fatty acids (SCFAs). Pyro-sequencing performed on human fecal flora (comprising some 10 trillion microbes) [2] reveals >5,600 bacterial taxa [3] dominated by Bacteroides (>90% of the composition of normal microbiomes), and Firmicutes, executing distinct, redundant, and complementary roles integral to human physiology. Perhaps only 300–500 species can be cultured in vitro [2]. Microbiomes reveal stability, durability, functional redundancy, and resiliency, despite dynamic compositional perturbations. However, our microbiome’s stability erodes when exposed to antibiotics and/or infections, wherein pathogenic microbiomes (fecal flora encompassing enteric pathogens) supersede [3, 4], perpetuated under host genetic and immune restriction [5]. Modernization has exposed our microbiome to altered diet (processed foods), sanitation/hygiene, and antibiotics, changing its composition. This may engender pathogenic local intestinal immunologic priming, activation, and immune bias. This immune dysregulation, loss of microbiome diversity, and colonization with enteric pathogens, termed “dysbiosis”, may potentiate chronic intestinal and extra-intestinal diseases, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) [1, 6]. Pathologic microbiomes may dominate the fecal flora within days of an adverse exposure, stabilizing with an altered flora (deviating from the host’s original flora) [7‐9]. Once established, antibiotic-resistant flora may persist for years in the absence of further antibiotic exposure. The protean deleterious pathophysiological repercussions manifest from persistent perturbation and/or shifts in composition, diversity, and ecological equilibrium of our coevolved microbiomes are becoming increasingly appreciated. These include refractory Clostridium difficile colitis (CDC; loss of colonization resistance to C. difficile and other enteric pathogens), IBD, and IBS. …