Coinfection and infection duration shape how pathogens affect the African buffalo gut microbiota.

Changes in the gut microbiota during pathogen infection are often predicted to influence disease outcomes. However, studies exploring whether pathogens induce microbiota shifts have yielded inconsistent results. This suggests that variation in infection, rather than the presence of infection alone, might shape pathogen-microbiota relationships. For example, most hosts are coinfected with multiple pathogens simultaneously, and hosts vary in how long they are infected, which may amplify or diminish microbial shifts expected in response to a focal pathogen. We used a longitudinal anthelmintic treatment study of free-ranging African buffalo (Syncerus caffer) to examine whether (i) coinfection with bovine tuberculosis (Mycobacterium bovis, TB) and gastrointestinal nematodes, and (ii) the duration of TB infection, modified effects of single pathogens on the gut microbiota. By accounting for the interaction between TB and nematodes, we found that coinfection affected changes in microbial abundance associated with single infections. Furthermore, the duration of TB infection predicted more microbiota variation than the presence of TB. Importantly, coinfection and infection duration had nearly as much influence on microbial patterns as demographic and environmental factors commonly examined in microbiota research. These findings demonstrate that acknowledging infection heterogeneities may be crucial to understanding relationships between pathogens and the gut microbiota.

Antibiotic Treatments for Clostridium difficile Infection Are Associated with Distinct Bacterial and Fungal Community Structures.

Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well known, it is unclear whether different forms of dysbiosis may potentially affect the course of CDI. How this is further influenced by C. difficile-directed antibiotics is virtually uninvestigated. In this study, diarrheal stool samples were collected from 20 hospitalized patients, half of whom were confirmed to have CDI. Analyzing tissue ex vivo and in duplicate, CDI and non-CDI fecal samples (n = 176) were either not antibiotic treated or treated with metronidazole, vancomycin, or fidaxomicin, the three most common CDI therapies. The microbial community composition, interactions, and predicted metabolic functions were assessed by 16S rRNA gene and internal transcribed spacer sequencing, bipartite network analysis, and phylogenetic investigation of communities by reconstruction of unobserved states. Our results demonstrate that while all C. difficile-directed antibiotics were associated with similar reductions in alpha diversity, beta diversity significantly differed on the basis of the particular antibiotic, with differentiating relative abundances of bacterial and fungal assemblages. With the exception of fidaxomicin, each antibiotic was associated with the emergence of potentially pathogenic fungal operational taxonomic units, with predicted bacterial functions enriched for xenobiotic metabolism that could perpetuate the dysbiosis driving CDI. Toxin-independent mechanisms of colitis related to the relative abundance of pathogenic bacteria and fungi were also noted. This study suggests that a transkingdom interaction between fungi and bacteria may be important in CDI pathophysiology, including being a factor in the historically high persistence and recurrence rates associated with this disease. IMPORTANCE Using human fecal samples and including sequencing for both bacterial and fungal taxa, this study compared the conventional antibiotics used to treat C. difficile infection (CDI) from the perspective of the microbiome, which is particularly relevant, given the relationship between dysbiotic states and the development of CDI. Sequencing and imputed functional analyses suggest that C. difficile-directed antibiotics are associated with distinct forms of dysbiosis that may be influential in the course of CDI. Further, a role for fungal organisms in the perpetuation of the causal dysbiosis of CDI is discussed, suggesting a previously unappreciated, clinically relevant transkingdom interaction that warrants further study.

The Microbial Ecosystem Distinguishes Chronically Diseased Tissue from Adjacent Tissue in the Sigmoid Colon of Chronic, Recurrent Diverticulitis Patients.

Diverticular disease is commonly associated with the older population in the United States. As individual's age, diverticulae, or herniation of the mucosa through the colonic wall, develop. In 10-25% of individuals, the diverticulae become inflamed, resulting in diverticulitis. The gut ecosystem relies on the interaction of bacteria and fungi to maintain homeostasis. Although bacterial dysbiosis has been implicated in the pathogenesis of diverticulitis, associations between the microbial ecosystem and diverticulitis remain largely unstudied. This study investigated how the cooperative network of bacteria and fungi differ between a diseased area of the sigmoid colon chronically affected by diverticulitis and adjacent non-affected tissue. To identify mucosa-associated microbes, bacterial 16S rRNA and fungal ITS sequencing were performed on chronically diseased sigmoid colon tissue (DT) and adjacent tissue (AT) from the same colonic segment. We found that Pseudomonas and Basidiomycota OTUs were associated with AT while Microbacteriaceae and Ascomycota were enriched in DT. Bipartite co-occurrence networks were constructed for each tissue type. The DT and AT networks were distinct for each tissue type, with no microbial relationships maintained after intersection merge of the groups. Our findings indicate that the microbial ecosystem distinguishes chronically diseased tissue from adjacent tissue.