Microbiota Dynamics in Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

Abstract

Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous colitis and is responsible for a large and increasing fraction of hospital-acquired infections. Fecal microbiota transplantation (FMT) is an alternate treatment option for recurrent C. difficile infection (RCDI) refractory to antibiotic therapy. It has recently been discussed favorably in the clinical and scientific communities and is receiving increasing public attention. However, short- and long-term health consequences of FMT remain a concern, as the effects of the transplanted microbiota on the patient remain unknown. To shed light on microbial events associated with RCDI and treatment by FMT, we performed fecal microbiota analysis by 16S rRNA gene amplicon pyrosequencing of 14 pairs of healthy donors and RCDI patients treated successfully by FMT. Post-FMT patient and healthy donor samples collected up to one year after FMT were studied longitudinally, including one post-FMT patient with antibiotic-associated relapse three months after FMT. This analysis allowed us not only to confirm prior reports that RCDI is associated with reduced diversity and compositional changes in the fecal microbiota, but also to characterize previously undocumented post-FMT microbiota dynamics. Members of the Streptococcaceae, Enterococcaceae, or Enterobacteriaceae were significantly increased and putative butyrate producers, such as Lachnospiraceae and Ruminococcaceae were significantly reduced in samples from RCDI patients before FMT as compared to post-FMT patient and healthy donor samples. RCDI patient samples showed more case-specific variations than post-FMT patient and healthy donor samples. However, none of the bacterial groups were invariably associated with RCDI or successful treatment by FMT. Overall microbiota compositions in post-FMT patients, specifically abundances of the above-mentioned Firmicutes, continued to change for at least 16 weeks after FMT, suggesting that full microbiota recovery from RCDI may take much longer than expected based on the disappearance of diarrheal symptoms immediately after FMT.

Fecal microbiota transplantation in children: a brief review

“…The intestinal microbiome of children, especially the very young, is known to differ from adults yet there is very little data characterizing associated microbiome changes with FMT in children. Microbiome changes have been reported in a 20-mo-old boy (28), with decreased diversity of the microbiome prior to FMT, with a relative abundance of Proteobacteria, with increased diversity after FMT with increasing Bacteroidetes; these are similar changes to those previously described in adults (39,42). Additionally, in a case series of older children increased microbiome diversity after FMT for CDI appears to be sustained in those without IBD, however at 6 mo decreases to pre-FMT baseline in those with IBD, suggesting IBD hostrelated mechanisms may modify fecal microbiome diversity (29).…”

“…In adults, prior to FMT for recurrent CDI, there is decreased bacterial diversity compared to healthy donors (39)(40)(41). After FMT, microbiota diversity increases in fecal samples and microbiome composition shifts towards the healthy donor (39).…”

“…After FMT, microbiota diversity increases in fecal samples and microbiome composition shifts towards the healthy donor (39). The intestinal microbiome of children, especially the very young, is known to differ from adults yet there is very little data characterizing associated microbiome changes with FMT in children.…”

Bloodstream infections in patients with liver cirrhosis

“…[27][28][29] In animal models of LC, portal hypertension and intestinal hypo-mobility lead to bacterial overgrowth in the small bowel and is considered the primum movens of translocation in these models. 30 In a clinical study of 24 patients with liver cirrhosis the bacterial overgrowth was enhanced by portal hypertension, as suggested by animal models.…”

Fecal Microbiota Transplantation Eliminates Clostridium difficile in a Murine Model of Relapsing Disease

“…Previous studies have suggested that patients who develop recurrence have a less diverse community than patients who have stable recovery (12). The idea that restoration of the gut microbiota is necessary to prevent or mitigate recurrence is supported by an ϳ90% success rate of fecal microbiota transplantation (FMT) (13), and significant recovery of diversity and community membership has been observed following FMT treatment for recurrent CDI (14)(15)(16). Future treatment options have thus concentrated on approaches that aid in recovery of colonization resistance.…”