Novel Gut Microbiota Modulator, Which Markedly Increases Akkermansia muciniphila Occupancy, Ameliorates Experimental Colitis in Rats

Tomkovich

Henry

et al. 2022

mBio

Antibiotic use, ubiquitous with the health care environment, is a major risk factor for Clostridioides difficile infection (CDI), the most common nosocomial infection. When C. difficile becomes resistant to antibiotics, a fecal microbiota transplant from a healthy individual can effectively restore the gut bacterial community and eliminate the infection.

Section: Discussionsupporting

confidence: 60%

Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine Communities

Tomkovich

Henry

et al. 2022

mBio

“…Enterobacteriaceae has been associated with C. difficile colonization and inflammation (14,23,24). Larger populations of Akkermansia were associated with preventing colonization, which we had previously observed, potentially indicating the maintenance of a protective mucus layer (14,(25)(26)(27). Increased populations of a select set of OTUs related to Porphyromonadaceae were also more abundant in mice that were resistant to colonization.…”

Section: Discussionsupporting

confidence: 58%

Simplified fecal community transplant restores Clostridioides difficile colonization resistance to antibiotic perturbed murine communities

Tomkovich

Henry

et al. 2022

Preprint

Fecal communities transplanted into individuals can eliminate recurrent Clostridioides difficile infection (CDI) with high efficacy. However, this treatment is only used once CDI becomes resistant to antibiotics or has recurred multiple times. We sought to investigate whether a fecal community transplant (FCT) pre-treatment could be used to prevent CDI altogether. We treated male C57BL/6 mice with either clindamycin, cefoperazone, or streptomycin, and then inoculated them with the microbial community from untreated mice before challenging with C. difficile. We measured colonization and sequenced the V4 region of the 16S rRNA gene to understand the dynamics of the murine fecal community in response to the FCT and C. difficile challenge. Clindamycin-treated mice became colonized with C. difficile but cleared it naturally and did not benefit from the FCT. Cefoperazone-treated mice became colonized by C. difficile, but the FCT enabled clearance of C. difficile. In streptomycin-treated mice, the FCT was able to prevent C. difficile from colonizing. Then we diluted the FCT and repeated the experiments. Cefoperazone-treated mice no longer cleared C. difficile. However, streptomycin-treated mice colonized with 1:102 dilutions resisted C. difficile colonization. Streptomycin-treated mice that received a FCT diluted 1:103, C. difficile colonized but later was cleared. In streptomycin-treated mice, inhibition of C. difficile was associated with increased relative abundance of a group of bacteria related to Porphyromonadaceae and Lachnospiraceae. These data demonstrate that C. difficile colonization resistance can be restored to a susceptible community with a FCT as long as it complements the missing populations.ImportanceAntibiotic use, ubiquitous with the healthcare environment, is a major risk factor for Clostridioides difficile infection (CDI), the most common nosocomial infection. When C. difficile becomes resistant to antibiotics, a fecal microbiota transplant from a healthy individual can effectively restore the gut bacterial community and eliminate the infection. While this relationship between the gut bacteria and CDI is well established, there are no therapies to treat a perturbed gut community to prevent CDI. This study explored the potential of restoring colonization resistance to antibiotic-induced susceptible gut communities. We described the effect gut bacteria community variation has on the effectiveness of a fecal community transplant for inhibiting CDI. These data demonstrated that communities susceptible to CDI can be supplemented with fecal communities but the effectiveness depended on the structure of the community following the perturbation. Thus, a simplified bacterial community may be able to recover colonization resistance to patients treated with antibiotics.

“…In our data, a population of Akkermansia , OTU 5, was most abundant in the nonmoribund mice with low histopathologic scores, but moribund mice had an increased population of Akkermansia OTU 8. This difference could indicate either a more protective mucus layer was present, inhibiting colonization ( 57 , 58 ), or mucus consumption by Akkermansia could have been cross-feeding C. difficile or exposing a niche for C. difficile ( 59 – 61 ). Similarly, Enterocloster was more abundant and associated with low histopathologic scores.…”

Section: Discussionmentioning

confidence: 99%

The Gut Bacterial Community Potentiates Clostridioides difficile Infection Severity

Schubert

Flynn

et al. 2022

mBio