Showing papers by "Emma Allen-Vercoe published in 2013"

Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'RePOOPulating' the gut.

Abstract: Fecal bacteriotherapy (‘stool transplant’) can be effective in treating recurrent Clostridium difficile infection, but concerns of donor infection transmission and patient acceptance limit its use. Here we describe the use of a stool substitute preparation, made from purified intestinal bacterial cultures derived from a single healthy donor, to treat recurrent C. difficile infection that had failed repeated standard antibiotics. Thirty-three isolates were recovered from a healthy donor stool sample. Two patients who had failed at least three courses of metronidazole or vancomycin underwent colonoscopy and the mixture was infused throughout the right and mid colon. Pre-treatment and post-treatment stool samples were analyzed by 16 S rRNA gene sequencing using the Ion Torrent platform. Both patients were infected with the hyper virulent C. difficile strain, ribotype 078. Following stool substitute treatment, each patient reverted to their normal bowel pattern within 2 to 3 days and remained symptom-free at 6 months. The analysis demonstrated that rRNA sequences found in the stool substitute were rare in the pre-treatment stool samples but constituted over 25% of the sequences up to 6 months after treatment. This proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis. This benefit correlates with major changes in stool microbial profile and these changes reflect isolates from the synthetic mixture. Clinical trial registration number: CinicalTrials.gov NCT01372943

Co-occurrence of anaerobic bacteria in colorectal carcinomas

Abstract: Numerous cancers have been linked to microorganisms. Given that colorectal cancer is a leading cause of cancer deaths and the colon is continuously exposed to a high diversity of microbes, the relationship between gut mucosal microbiome and colorectal cancer needs to be explored. Metagenomic studies have shown an association between Fusobacterium species and colorectal carcinoma. Here, we have extended these studies with deeper sequencing of a much larger number (n = 130) of colorectal carcinoma and matched normal control tissues. We analyzed these data using co-occurrence networks in order to identify microbe-microbe and host-microbe associations specific to tumors. We confirmed tumor over-representation of Fusobacterium species and observed significant co-occurrence within individual tumors of Fusobacterium, Leptotrichia and Campylobacter species. This polymicrobial signature was associated with over-expression of numerous host genes, including the gene encoding the pro-inflammatory chemokine Interleukin-8. The tumor-associated bacteria we have identified are all Gram-negative anaerobes, recognized previously as constituents of the oral microbiome, which are capable of causing infection. We isolated a novel strain of Campylobacter showae from a colorectal tumor specimen. This strain is substantially diverged from a previously sequenced oral Campylobacter showae isolate, carries potential virulence genes, and aggregates with a previously isolated tumor strain of Fusobacterium nucleatum. A polymicrobial signature of Gram-negative anaerobic bacteria is associated with colorectal carcinoma tissue.

Microbial ecosystems therapeutics: a new paradigm in medicine?

Abstract: Increasing evidence indicates that the complex microbial ecosystem of the human intestine plays a critical role in protecting the host against disease. This review discusses gut dysbiosis (here defined as a state of imbalance in the gut microbial ecosystem, including overgrowth of some organisms and loss of others) as the foundation for several diseases, and the applicability of refined microbial ecosystem replacement therapies as a future treatment modality. Consistent with the concept of a ‘core’ microbiome encompassing key functions required for normal intestinal homeostasis, ‘Microbial Ecosystem Therapeutics’ (MET) would entail replacing a dysfunctional, damaged ecosystem with a fully developed and healthy ecosystem of ‘native’ intestinal bacteria. Its application in treating Clostridium difficile infection is discussed and possible applications to other diseases such as ulcerative colitis, obesity, necrotising enterocolitis, and regressive-type autism are reviewed. Unlike conventional probiotic thera...

Colonizing the embryonic zebrafish gut with anaerobic bacteria derived from the human gastrointestinal tract.

Abstract: The zebrafish has become increasingly popular for microbiological research. It has been used as an infection model for a variety of pathogens, and is also emerging as a tool for studying interactions between a host and its resident microbial communities. The mouse microbiota has been transplanted into the zebrafish gut, but to our knowledge, there has been no attempt to introduce a bacterial community derived from the human gut. We explored two methods for colonizing the developing gut of 5-day-old germ-free zebrafish larvae with a defined anaerobic microbial community derived from a single human fecal sample. Both environmental exposure (static immersion) and direct microinjection into the gut resulted in the establishment of two species-Lactobacillus paracasei and Eubacterium limosum-from a community of 30 strains consisting of 22 anaerobic species. Of particular interest is E. limosum, which, as a strict anaerobe, represents a group of bacteria which until now have not been shown to colonize the developing zebrafish gut. Our success here indicates that further investigation of zebrafish as a tool for studying human gut microbial communities is warranted.

Artificial stool transplantation: progress towards a safer, more effective and acceptable alternative

Abstract: Expert Rev. Gastroenterol. Hepatol. 7(4), 291–293 (2013) “RePOOPulate, produced to order through bacterial culture, was instilled into two patients with severe, recurrent Clostridium difficile infection via colonoscope as part of a proof-of-principle trial, with resolution of disease in both cases.”