Heekuk Park

Fecal Microbial Transplants Reduce Antibiotic-resistant Genes in Patients With Recurrent Clostridium difficile Infection

Patients with recurrent C. difficile infection harbor large numbers of microbes with antibiotic resistance genes. Fecal microbial transplantation eradicates pathogenic organisms and eliminates antibiotic-resistance genes suggesting this may be a viable treatment option to eradicate multidrug resistant bacteria from patients.

Fecal microbiota transplantation in the management of hepatic encephalopathy

H epatic encephalopathy (HE) is a common and debilitating complication of end-stage liver cirrhosis. It is associated with poor quality of life, a significant burden on health care, and increased mortality. Ammonia generated by the enteric bacteria is a critical driver of HE. The current treatment is lactulose and/or rifaximin, both of which target the gut microbiota. As dysbiosis is thought to contribute to HE, we hypothesized that manipulating the gut microbiome through fecal microbiota transplantation (FMT) could reverse intestinal dysbiosis and result in cognitive improvement in overt HE. Health Canada approval was obtained to proceed with the study.

Endospore forming bacteria may be associated with maintenance of surgically-induced remission in Crohn’s disease

Crohn’s disease (CD) patients who undergo ileocolonic resection (ICR) typically have disease recurrence at the anastomosis which has been linked with a gut dysbiosis. The aims of this study were to define the mucosa-associated microbiota at the time of ICR and to determine if microbial community structure at the time of surgery was predictive of future disease relapse. Ileal biopsies were obtained at surgery and after 6 months from CD subjects undergoing ICR. Composition and function of mucosal-associated microbiota was assessed by 16S rRNA sequencing and PICRUSt analysis. Endoscopic recurrence was assessed using the Rutgeerts score. Analysis of mucosal biopsies taken at the time of surgery showed that decreased Clostridiales together with increased Enterobacteriales predicted disease recurrence. An increase in the endospore-forming Lachnospiraceae from surgery to 6 months post-ICR was associated with remission. A ratio of 3:1 between anaerobic endospore-forming bacterial families and aerobic families within the Firmicutes phylum was predictive of maintenance of remission. Gut recolonization following ICR is facilitated by microbes which are capable of either aerobic respiration or endospore formation. The relative proportions of these species at the time of surgery may be predictive of subsequent microbial community restoration and disease recurrence.

Prebiotic Supplementation Following Ileocecal Resection in a Murine Model is Associated With a Loss of Microbial Diversity and Increased Inflammation

Background Individuals with Crohns disease frequently require ileocecal resection (ICR), and inflammation often recurs in the neoterminal ileum following surgery. Fructooligosaccharide (FOS) is a fermentable prebiotic that stimulates the growth of bifidobacteria and may promote anti-inflammatory activity. The aim of this study was to determine if supplementation of a postICR diet with FOS in a mouse model would be effective in stimulating the growth of bifidobacteria and reducing systemic and local inflammation. Methods ICR was performed in IL10-/- mice (129S1/SvlmJ) with colitis. Following surgery, nonICR control and ICR mice were fed a chow diet ± 10% FOS for 28 days. Serum, colon, and terminal ileum (TI) were analyzed for cytokine expression by MesoScale discovery platform. DNA extracted from stool was analyzed using 16s rRNA sequencing and qPCR. Expression of occludin and ZO1 was assessed using qPCR. Short-chain fatty acid (SCFA) concentrations were assessed using gas chromatography. Results ICR led to increased systemic inflammation (P < 0.05) and a significant decline in fecal microbial diversity (P < 0.05). Mice on the FOS diet had a greater reduction in microbial diversity and also had worsened inflammation as evidenced by increased serum IL-6 (P < 0.05) and colonic IFNγ and TNFα (P < 0.05). Expression of occludin and ZO1 were significantly reduced in FOS-supplemented mice. There was a correlation between loss of diversity and the bifidogenic effectiveness of FOS (r = -0.61, P < 0.05). Conclusions FOS-supplementation of a postICR diet resulted in a decrease in fecal bacterial diversity, reduction in barrier function, and increased gut inflammation.

A Distinctive Urinary Metabolomic Fingerprint Is Linked With Endoscopic Postoperative Disease Recurrence in Crohn’s Disease Patients

Background Crohns disease (CD) patients who undergo ileocolonic resection frequently have disease recurrence. The aim of this preliminary study was to identify urinary metabolomic profiles associated with disease recurrence in order to identify underlying mechanisms of recurrence and possible disease biomarkers. Methods Biopsies from the neoterminal ileum were collected from CD patients (n = 38) after ileocolonic resection in order to assess mucosa-associated microbiota using 16S rRNA multitag pyrosequencing. Urine samples were collected, and metabolomic profiling was done using high-resolution nuclear magnetic resolution spectroscopy and a combined direct infusion liquid chromatography tandem mass spectrometry. The Rutgeerts scoring system was used to assess endoscopic postoperative recurrence of CD. Results There were 28 (73.7%) patients with endoscopic CD recurrence. CD patients who were in endoscopic remission had a higher abundance of Bacteroidetes and lower abundance of Fusobacteria and Proteobacteria in comparison with CD patients who had endoscopic recurrence. In addition, metabolomic profiling could also discriminate between these 2 groups of patients. Endoscopic recurrence was associated with increased concentration of urinary levoglucosan. Rutgeerts score was positively correlated with levoglucosan and propylene glycol levels. Conclusions CD patients who present with endoscopic disease recurrence after surgery have a unique urinary metabolomic fingerprint that can differentiate them from CD patients who are in endoscopic remission after ileocolonic resection. In addition, mucosal-associated microbiota in CD patients with or without disease recurrence after surgery differs and correlates with some urinary metabolites.