Healing effect of faecal transplantation lasts a long time

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Intestinal microbiota can be modified relatively permanently, found a Finnish study, opening new possibilities for the use this treatment for other diseases related to microbial dysbiosis.

The researchers at the University of Helsinki and Helsinki University Hospital have studied in detail the intestinal microbiota of 14 patients treated with a faecal microbiota transplant. The patients suffered from recurrent Clostridium difficile -infection, also known as antibiotic associated diarrhoea, and they had not responded to antibiotic treatment. After the faecal microbiota transplantation therapy, the patient’s microbiota was followed for a year.

The researchers found out that the patient’s intestinal microbiota highly resembled the donor’s microbiota and this composition remained stable through-out the 1-year follow-up period.

“Our results suggest that intestinal microbiota can be modified relatively permanently. This opens new possibilities to the use this treatment for other diseases related to microbial dysbiosis,” says the Academy research fellow Reetta Satokari from the University of Helsinki.

The researchers also wanted to find out which bacteria among the diverse microbial community are the key species behind the treatment success. In order to understand this, they investigated which bacteria were commonly transferred from the donors to all of the patients. In the future, the promising bacterial species will be isolated and characterised for the design of bacterio-therapy products.

“The aim is to develop a so-called bacterial cocktail that could be used to treat patients instead of the faecal material,” outlines the post-doctoral researcher Jonna Jalanka.

Reetta Satokari’s group has an interesting ongoing project where they look at the effects of faecal microbiota transplant on antibiotic resistance genes detected in the patient’s microbiota. The group just published a study where they showed that the transplant decreases the amount of antibiotic resistant genes found in the patient´s intestinal microbiota.

“This is a very important finding because resistance to antibiotics is a big problem and resistant bacterial strains are often found in the intestine,” says Satokari.

Faecal microbiota transplantation is an established treatment method for severe antibiotic-associated diarrhoea where medical treatment has not cleared the infection. It has a high success rate, where over 90% of the patients are cured.

“We treat patients with this method in all university hospitals and most of the central hospitals in Finland,” tells chief physician Dr Perttu Arkkila from the Helsinki University Hospital endoscopy unit. “Currently, we have ongoing clinical trials where we are investigating the effect of faecal microbiota transplantation in treating irritable bowel syndrome and inflammatory bowel disease.”

Arkkila also told that the patients are very eager to enroll the trials since they have often suffered from their condition for a long time and have not found a relief. The prospective donors are selected carefully. They should be in good general health, normal weight and not have had any antibiotics for the past half a year. Also all donors are tested carefully to exclude several diseases.

The importance of the intestinal microbiota for human health has just recently been unfolded. The relationship between the human health and intestinal microbiota has been widely investigated and it has been recently linked with several different conditions, including over-weight.

“This is currently a very hot research topic,” states Satokari.

Abstract
Background: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). It restores the disrupted intestinal microbiota and subsequently suppresses C. difficile. The long-term stability of the intestinal microbiota and the recovery of mucosal microbiota, both of which have not been previously studied, are assessed herein. Further, the specific bacteria behind the treatment efficacy are also investigated.
Methods: We performed a high-throughput microbiota profiling using a phylogenetic microarray analysis of 131 faecal and mucosal samples from 14 rCDI patients pre- and post-FMT during a 1-year follow-up and 23 samples from the three universal donors over the same period.
Results: The FMT treatment was successful in all patients. FMT reverted the patients’ bacterial community to become dominated by Clostridium clusters IV and XIVa, the major anaerobic bacterial groups of the healthy gut. In the mucosa, the amount of facultative anaerobes decreased, whereas Bacteroidetes increased. Post-FMT, the patients’ microbiota profiles were more similar to their own donors than what is generally observed for unrelated subjects and this striking similarity was retained throughout the 1-year follow-up. Furthermore, the universal donor approach allowed us to identify bacteria commonly established in all CDI patients and revealed a commonly acquired core microbiota consisting of 24 bacterial taxa.
Conclusions: FMT induces profound microbiota changes, therefore explaining the high clinical efficacy for rCDI. The identification of commonly acquired bacteria could lead to effective bacteriotherapeutic formulations. FMT can affect microbiota in the long-term and offers a means to modify it relatively permanently for the treatment of microbiota-associated diseases.

Authors
Jonna Jalanka, Eero Mattila, Hanne Jouhten, Jorn Hartman, Willem M de Vos, Perttu Arkkila, Reetta Satokari

University of Helsinki material
BMC Medicine abstract


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