Fecal Micobiota Transplantation to Treat Sepsis of Unclear Etiology*

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Providing normal feces to the intestinal tract of a patient suffering from life-threatening infection dates back to the fourth century when the Chinese medical literature described treating food poisoning with fecal material known as “golden soup (1).” German soldiers stationed in Northern Africa during World War II reported that natives consumed camel feces to treat dysentery (2). With this historical perspective in mind, the recent and remarkable success we are witnessing with fecal microbial transplantation (FMT) to treat recalcitrant Clostridium difficile colitis seems to make sense. If the gut ecosystem is so disturbed that it cannot be reordered with antibiotics, FMT therapy sounds rather straightforward: reestablish the normal microbial ecosystem in the gut by introducing feces from a healthy donor. Now with data from several hundred patients suffering from C. difficile colitis demonstrating remarkable success, administration of an FMT, either via nasogastric tube or via colonoscopy, appears to be highly efficacious when a gut pathogen is causing life-threatening sepsis (3, 4). As such, it now seems logical, if not opportune, to extent this therapeutic concept to other disorders in which a gut pathogen or community of pathogens may be causing life-threatening sepsis.
In the present study by Wurm et al (5), published in this issue of Critical Care Medicine, three, relatively young, patients were admitted to ICUs at Medical University of Graz in Austria for various reasons and symptomatology. During their ICU admission, each patient developed severe, high volume diarrhea. The authors proposed that the common factor linking the three patients was previous exposure to antimicrobial and steroidal therapy, both of which are known to disrupt the microbiome and cause alterations in epithelial permeability (6, 7). Each patient underwent upper and lower gastrointestinal endoscopy with biopsy. Histopathologically, the biopsy specimens demonstrated near total crypt loss and severe villus blunting in the small intestine and varying severity of crypt and epithelial loss in the colon. Two of the patients underwent an extensive microbiota analysis. Fecal samples initially showed an overabundance of proteobacteria and a diminution in bacteroides and firmicutes. As the disease progressed, the diversity of the microbiota and organismal dominance underwent extreme fluctuations. The “richness” of the microbiota remained reduced compared to samples from control subjects throughout the clinical course. The predominant bacterial species varied in character with Pseudomonas and Enterococcus emerging in one patient and Lactobacillus and Haemophilus in the other prior to and after treatment with a probiotic. One patient underwent FMT consisting of 61% bacteroides and 37% firmicutes. The authors reported a continuous decline in stool burden and evidence of regenerating crypts and epithelial lining by day 7 following the FMT. Although Haemophilus colonization was initially overtaken by Enterococcus following the FMT, physiologic proportions of bacteroides and firmicutes were eventually reestablished. The authors concluded that the observed “apoptosis,” characterized by crypt and epithelial loss, may be the consequence of the physiologic alterations from a highly disturbed microbiome. In this circumstance, administration of an FMT could potentially reestablish epithelial homeostasis.
The role that the normal microbiota play to maintain epithelial structure and function is now well-established. Work from our laboratory and others has demonstrated that the microbiota plays a key role in maintaining the regenerative capacity of the intestinal epithelium (8). This appears to be especially prominent within crypts in the cecum, the area of the intestinal track with the greatest physical density and biomass of bacteria. Cecal crypts lose their microbiota in response to environmental stressors (i.e., surgical injury) and antimicrobial therapy.

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