StemCell Therapy

The team points to the increase of IL-25, an important agent of the immune system, in the recipient post-transplant, which led to a decrease in damaging tissue inflammation.

The University of Virginia (UVA) School of Medicine team conclude changes triggered by the transplants, including beneficial gene activity changes, support the immune system in battling recurrent C. difficile infection.

Even though we know that faecal microbiota transplants can treat recurrent C. difficile infection, we don't know exactly why some microbe combinations work better than others or why the same combinations can have different effects on different people, explains researcher Ning-Jiun "Ninj" Jan, of UVA's Division of Infectious Disease and International Health.

We believe that this variability stems from each person's immune system being unique. That is why it is important for us to find out what immune markers change in patients where faecal microbiota transplantation was successful in preventing C. difficile re-infections.

"Finding that a specific immune signalling molecule, IL-25, was increased in successful faecal microbiota transplantations indicated that maybe IL-25 can be used as an adjunctive therapy for treating C. difficile infection."

The discovery was made after previous efforts by the team found dysbiosis in a mouse model of CDI reduced activity of interleukin 25 (IL-25) in the colon. FMT appeared to restore this IL-25 signalling.

This study involved taking colonic biopsy specimens and blood from patients at the time of FMT and 60days later.

These specimens were analysed for IL-25 protein levels, total tissue transcriptome, and epithelium-associated microbiota before and after FMT, and peripheral immune cells were immunophenotyped.

Findings suggested FMT increased diversity of the colonic microbiota and levels of IL-25 in colonic tissue.

Furthermore, FMT increased expression of homeostatic genes and repressed inflammatory genes.

Circulating Th17 cells, which play a key role in healthy immune system function were decreased in numbers post-FMT.

The transplants also increased the diversity of the microbes that naturally live in human colons, according to the researchers.

The increase in levels of the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity, suggests the study, which appears in the journal mSphere.

Despite the increasing use of FMT for treatment of rCDI, the mechanisms of action of FMT are poorly defined.

FMTs inhibitory effects on C. difficile may occur via niche exclusion, nutrient competition, and the production of antimicrobial peptides, according to past studies looking into this approach.

FMT may also promote changes in the host intestinal epithelium that increase resistance to recurrence of disease via fortification of the mucus layer and differentiation and proliferation of intestinal epithelial cells.

One reason the mechanisms of FMT are unclear is that host immune responses can vary greatly and have complex effects on C. difficile infection severity, as well as the efficacy of FMT.

Type 1 responses via type 1 innate lymphoid cells (ILC1s) have been shown to be protective, type 17 immune responses have been related to increased host damage, and type 2 immune responses via ILC2s have been related to tissue repair via eosinophil recruitment.

"In the future it may be possible to combine faecal microbiota transplants with cytokine-based therapies to increase the success rate of treatment," adds Jan.

"There is a lot of interplay between our immune system and our intestinal microbes, and it's exciting that understanding their relationship is helping us find new therapies."

Source: mSphere

Published online: http://dx.doi.org/10.1128/mSphere.00669-21

Fecal Microbiota Transplantation Increases Colonic IL-25 and Dampens Tissue Inflammation in Patients with Recurrent Clostridioides difficile.

Authors: N. Jan et al.

Link:
Team puts forward FMT insight into its success against C. difficile infection - NutraIngredients.com

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