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Fecal Transplantation Alters Rat Gut Microbiomes

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – A study in the early, online edition of Genome Research today suggests it's possible to produce long-term changes to the rat gut microbiome through fecal transplants.

Spanish and American researchers used deep sequencing and phylogenetics to characterize and compare gut microbial communities in healthy fecal donor rats and more than a dozen rats from another strain, including control rats and rats that had received fecal transplants alone or after antibiotic treatment. Their findings indicate that fecal transplantation does lead to changes in gut microbiomes that persist over time.

"The transplantation produced a marked increase in the microbial diversity of the recipients, which stemmed from both capture of new phylotypes and increase in abundance of others," corresponding author Chaysavanh Manichanh, a researcher with the University Hospital Vall d’Hebron Research Institute in Spain, and co-authors wrote.

"The results were surprising, and indicated that the indigenous gut microbial composition could be reshaped to an extent not anticipated in previous studies," they added.

But rather than improving the efficiency of the fecal transplant process, the team noted, giving rats antibiotics prior to transplantation actually seems to hinder successful microbiome replacement.

"[L]owering the recipient bacterial load by antibiotic intake prior to transplantation did not increase establishment of the donor phylotypes," they explained, "although some dominant lineages still transferred successfully."

More than 1,000 microbial species are found in the mammalian gut. And mounting research — including the Human Microbiome Project — is addressing the role that microbes in the gut and elsewhere have in health and disease.

For instance, past studies have looked at how the human gut microbiome influences obesity and malnutrition. And research suggests the microbial community in the gut differs in individuals with some diseases, such as Crohn's disease and ulcerative colitis.

Consequently, some researchers are investigating the possibility of treating individuals with gastrointestinal and other health problems using fecal transplants from healthy individuals.

For the current study, Manichanh and his co-workers used the Roche 454 Genome Sequencer FLX to metagenomically sequence the V4 hyper-variable region of the 16S gene from pooled fecal samples collected from 18 rats.

Four rats from Sprague Dawley and Wistar strains were used as fecal donors, while another 14 rats from the Lewis strain served as control or recipient rats.

After transferring feces from the cecum of donor rats into recipient rats, including a subset that had been given vancomycin and imipenem for three days, the team collected dozens of fecal samples and investigated the density and diversity of gut microbes in donor, recipient, and control rats at various times.

The researchers detected roughly 2,621 bacterial phylotypes in the samples tested, including microbes from eight or more bacterial divisions.

In general, bacteria from the Firmicutes and Bacteroidetes phyla were most common in these microbiomes, they noted.

And based on comparisons with samples for two healthy women, the team estimated that the rat gut microbiome is some two to three times more diverse than microbial communities in human guts.

Prior to transplantation, the researchers found 341 phylotypes in pooled samples from the four donor rats and an average of 229 phylotypes from recipient rat samples.

One month after fecal transplantation, though, recipient rats had gut microbiome profiles that were more similar to the donor rats than to pre-transplant recipient rats — a pattern that also held another two months later, though with a bit more variation.

In contrast, recipient rats that received antibiotics prior to fecal transplantation had distinct gut microbiome patterns.

While antibiotic treatment generally cut the diversity and density of microbes in rat guts, donor microbes didn't seem to take hold as well in these rats as they did in the guts of untreated recipients.

Antibiotic-treated rats had gut microbiomes showing less diversity, more Firmicutes bacteria, and fewer Bacteroidetes than other rats, researchers explained. But when rats were given antibiotics before receiving the fecal transplants, their gut microbial patterns fell between those detected in the rats given antibiotics alone and those given fecal transplants but no antibiotics

"Phylogenetic clustering indicates that combination of both treatments simply produces a combination of their reshaping effects," the researchers explained. "Although this finding makes ecological sense … it is a highly counter-intuitive result that should be taken into account in designing future bacteriotherapy protocols."

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