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Small Bowel Transplant Alters Gut Microbiome

NEW YORK (GenomeWeb News) – New genetic and metabolomic research suggests small bowel transplantation can shift the microbial community present in the gut — likely by exposing the microbes to more oxygen than usual.

In a paper scheduled to appear online this week in the Proceedings of the National Academy of Sciences, researchers from the University of California at Davis, Johns Hopkins University, and Georgetown University used ribosomal DNA sequencing and quantitative PCR to catalog the microbes in the last bit of the small intestine, called the ileum, in nearly 20 individuals who had received small bowel transplants.

Their results suggest that patients who have surgery-related openings linking their small bowel to the outside of their body typically have microbiomes containing bugs that can survive in the presence of oxygen — a shift from the strictly anaerobic microbes that usually preside in the gut.

"Our study of the microbiota associated with the transplanted human small bowel revealed that the small bowel can function with either of two alternative microbial populations," senior author Jonathan Eisen, an evolutionary biologist at UC Davis, and his co-authors wrote.

Small bowel transplants are intended to treat intestinal failure — problems with nutrient uptake in the intestine — by increasing the bowel length so individuals have more surface area for nutrient absorption. Nevertheless, Eisen and his co-authors explained, the surgery carries a high rejection risk.

As part of their effort to explore the consequences of small bowel transplantation, the researchers decided to characterize the microbiome in patients who had received the surgery.

During the procedure, doctors typically leave a small opening between the small bowel and the outside of the body in order to help keep an eye on the transplant. This opening, called an ileostomy, also offers an opportunity to monitor the microbes within the individual's small intestine over time.

"This project represented a very unique opportunity to study the recolonization of the ileum, or small bowel, after a disturbance — transplantation — much like studying re-growth of a forest after clear cutting," Eisen said in a statement.

The researchers focused on17 individuals who were participating in a study at Georgetown's Transplant Institute. To start with, the team randomly picked nine of the patients, taking ileal effluent samples an average of 70 days after surgery. They then generated 1,892 microbial 16S rDNA sequences at the US Department of Energy's Joint Genome Institute.

Since nearly all of the species they detected belonged to four bacterial orders, the researchers decided to do their subsequent studies with qPCR rather than direct sequencing — an approach geared at not only saving time and money, but also at getting a more quantitative view of the microbes.

The team collected more than 250 small bowel samples from the 17 participants, who were each sampled at least ten times after their surgery and evaluated 229 of the samples using qPCR. In so doing, they found that individuals who still had open ileostomies tended to have small bowel microbiomes dominated by facultative anaerobes — which can use oxygen but don't require it for their growth — such as Lactobacilli and Enterobacteria.

In contrast, they explained, the small bowel microbiome is usually comprised of strictly anaerobic bacteria from the Bacteroides or Clostridia groups.

When they used colonoscopies to take small bowel samples from ten patients who had their ileostomies closed, the researchers found that the gut microbiome shifted back to its original anaerobic composition after ileostomy closure.

Based on these results the researchers suspected that oxygen introduced into the small bowel during surgery and through the open ileostomy alters the microbiome, making it more oxygen tolerant.

Indeed, when they compared the metabolomic profiles in the transplant patient small bowels before and after ileostomy closure using gas chromatography time-of-flight mass spectrometry, the team found that the individuals who had open ileostomies also had bacterial metabolites in their gut that were consistent with oxygen use.

"Until the ileostomy is surgically closed, the bacterial population present is dominated by facultative anaerobes, whereas after closure, and in the normal ileum, strict anaerobes prevail," the authors concluded. "The alternative states described in this study suggest that the ecological possibilities within the human gut are broader than previously realized."

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