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The Gut Microbiota Is Associated with Clearance of Clostridium difficile Infection Independent of Adaptive Immunity.

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PubMed ID: 30700514

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Leslie JL, Vendrov KC, Jenior ML, Young VB

mSphere. 01 2019

COMMENT: This study investigates the role of the adaptive immune system and gut microbiota in modulating C. difficile colonization. To this end, the authors compared C. difficile infection in wild-type (WT) and RAG1−/− mice (which lack B and T cells). The results demostrate that clearance of C. difficile can occur in the absence of adaptive immunity. The gut microbial community of the mice was examined over the course of the experiment using 16S rRNA gene amplicon sequencing of the V4 region. The mice that eventually cleared C. difficile had significantly distinct community compared to the mice that remained colonized.

Objective:

In this study, we sought to determine whether adaptive immunity plays a role in clearance of C. difficile colonization.

Main results

Results from multiple experimental models lead us to conclude that clearance of C. difficile in mice can occur without contributions from adaptive immune responses.

Our results show that reconstitution of adaptive immunity is associated with altered abundance of some bacteria in the gut; however, it does not impact levels of C. difficile colonization. We found that in the reconstituted RAG1−/− mice that developed serum IgG, there was a decreased abundance of Akkermansia (OTU 3).

In the two mice that received splenocytes but did not have detectable serum IgG, the abundance of the Akkermansia OTU was very low

we used random forest to eventually identify just two OTUs that could classify mice that would go on to clear C. difficile with 66.6% accuracy. (…) Both of the OTUs we identified belong to the family Lachnospiraceae and were enriched in mice that would go on to clear C. difficile infection.

Our results suggest that community resilience is intrinsic to the community membership at baseline, prior to any antibiotic treatment


Conclusions

Finally, our findings have implications for the design of future preclinical studies testing the efficacy of vaccines or other manipulations of adaptive immunity on the level of colonization as “cage effects,” or inherent differences in the baseline community structure of animals within cages may bias findings. Experimental approaches that can be implemented to account for the role of the microbiota include cohousing, using multiple cages for each experimental condition, and the use of littermate controls

Contributor

Diana López-Farfán