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Food and Drug Administration approval of the first microbiome therapies represents a true expansion the treatment paradigm for Clostridioides difficile but raises new questions about the future role of fecal microbiota transplantation. The authors outline the advances in microbiome therapeutic development that have addressed fecal microbiota transplantation's (FMT's) inherent limitations of safety and scalability. The authors also suggest that as microbiome therapeutic development continues for other indications, FMT will likely remain a necessary model of human microbiota dynamics for translational research. [ABSTRACT FROM AUTHOR]

Background Ventilator-associated lower respiratory tract infection (VA-LRTI) is common among critically ill patients and has been associated with increased morbidity and mortality. In acute critical illness, respiratory microbiome disruption indices (MDIs) have been shown to predict risk for VA-LRTI, but their utility beyond the first days of critical illness is unknown. We sought to characterize how MDIs previously shown to predict VA-LRTI at initiation of mechanical ventilation change with prolonged mechanical ventilation, and if they remain associated with VA-LRTI risk. Methods We developed a cohort of 83 subjects admitted to a long-term acute care hospital due to their prolonged dependence on mechanical ventilation; performed dense, longitudinal sampling of the lower respiratory tract, collecting 1066 specimens; and characterized the lower respiratory microbiome by 16S rRNA sequencing as well as total bacterial abundance by 16S rRNA quantitative polymerase chain reaction. Results Cross-sectional MDIs, including low Shannon diversity and high total bacterial abundance, were associated with risk for VA-LRTI, but associations had wide posterior credible intervals. Persistent lower respiratory microbiome disruption showed a more robust association with VA-LRTI risk, with each day of (base e) Shannon diversity <2.0 associated with a VA-LRTI odds ratio of 1.36 (95% credible interval, 1.10–1.72). The observed association was consistent across multiple clinical definitions of VA-LRTI. Conclusions Cross-sectional MDIs have limited ability to discriminate VA-LRTI risk during prolonged mechanical ventilation, but persistent lower respiratory tract microbiome disruption, best characterized by consecutive days with low Shannon diversity, may identify a population at high risk for infection and may help target infection-prevention interventions. [ABSTRACT FROM AUTHOR]

In people, colonization with Clostridioides difficile, the leading cause of antibiotic-associated diarrhea, has been shown to be associated with distinct gut microbial features, including reduced bacterial community diversity and depletion of key taxa. In dogs, the gut microbiota features that define C. difficile colonization are less well understood. We sought to define the gut microbiota features associated with C. difficile colonization in puppies, a population where the prevalence of C. difficile has been shown to be elevated, and to define the effect of puppy age and litter upon these features and C. difficile risk. We collected fecal samples from weaned (n = 27) and unweaned (n = 74) puppies from 13 litters and analyzed the effects of colonization status, age and litter on microbial diversity using linear mixed effects models. Colonization with C. difficile was significantly associated with younger age, and colonized puppies had significantly decreased bacterial community diversity and differentially abundant taxa compared to non-colonized puppies, even when adjusting for age. C. difficile colonization remained associated with decreased bacterial community diversity, but the association did not reach statistical significance in a mixed effects model incorporating litter as a random effect. Even though litter explained a greater proportion (67%) of the variability in microbial diversity than colonization status, we nevertheless observed heterogeneity in gut microbial community diversity and colonization status within more than half of the litters, suggesting that the gut microbiota contributes to colonization resistance against C. difficile. The colonization of puppies with C. difficile has important implications for the potential zoonotic transfer of this organism to people. The identified associations point to mechanisms by which C. difficile colonization may be reduced. [ABSTRACT FROM AUTHOR]

A substantial proportion of Clostridium difficile infection (CDI) cases recur after completion of antibiotic therapy, and antibiotic cure rates diminish with each recurrence of CDI. Fecal microbiota transplantation (FMT) is an effective therapy for recurrent FMT, which otherwise requires prolonged or indefinite antibiotic treatment. FMT is performed by introducing the fecal microbial community obtained from a healthy donor or pool of donors into the stomach, small intestine, or colon of a patient with CDI. Multiple clinical trials support the usefulness of FMT in treating recurrent CDI, and CDI treatment guidelines now include consideration of FMT at the third CDI recurrence. However, there remain challenges to incorporating FMT into clinical practice. First, methods of fecal bacterial community processing vary, as do methods of FMT administration. Second, the optimal dosing strategy and expected benefit of FMT for refractory CDI, particularly for severe and severe complicated cases, are uncertain. Third, the US Food and Drug Administration (FDA) considers FMT an investigational treatment. Fourth, insurance reimbursement for FMT usually falls short of FMT administration costs. In the setting of rising C difficile incidence and growing evidence for FMT efficacy, the demand for FMT has increased. However, uncertainty surrounding optimal FMT preparation and administration methods, FDA oversight, and insurance reimbursement presently limits the clinical practice of FMT. [ABSTRACT FROM AUTHOR]

Background Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated and health care–associated diarrhea in humans. Recurrent CDI (R-CDI) occurs in ~20%–30% of patients with CDI and results in increased morbidity, mortality, and hospital costs. Genomic analyses have shown overlap of C. difficile isolates from animals and people, suggesting that a zoonotic reservoir may contribute to recurrence. The objective of this study was to determine whether pet ownership is a risk factor for recurrence of CDI. Methods We conducted a case–control study among patients with recurrent CDI (cases; n = 86) and patients with nonrecurrent CDI (controls; n = 146). Multivariable logistic regression modeling was used to determine the association between recurrence of CDI and pet ownership while accounting for patient-level risk factors. Results Pet ownership was not significantly associated with recurrence of CDI (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.38–2.72; P  = 0.965) among all patients (n = 232). However, among the subset of patients with community-associated or community-onset health care facility–acquired CDI (n = 127), increasing contact with pets was increasingly protective against recurrence: for every point increase in a pet contact score (out of 7 possible points), the odds of recurrence decreased by 14% (OR, 0.86; 95% CI, 0.74–1.00; P  = 0.051). Conclusions Close interactions with pets appear protective against the recurrence of community-acquired CDI. A potential mechanism may involve beneficial contributions to the microbiota of pet owners afflicted with CDI, as has been observed for other conditions such as atopy, obesity, and food allergies. However, more research is needed to understand the interactions between pets, owners, and their microbiota. [ABSTRACT FROM AUTHOR]