Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in Clostridioides difficile Infection

Stewart, David B.; Wright, Justin; Fowler, Maria; McLimans, Christopher J.; Tokarev, Vasily; Amaniera, Isabella; Baker, Owen; Wong, Hoi‐Tong; Brabec, Jeffrey L.; Drucker, Rebecca; Lamendella, Regina

doi:10.1128/msphere.00454-19

Cited by 37 publications

(62 citation statements)

References 38 publications

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“…Their findings demonstrated an increase in the family Pichiaceae of the order Saccharomycetales , while in CDI patients, relative abundance was observed in the phylum Ascomycota , the order Pleosporales and the class Dothideomycetes . This interkingdom interaction in CDI patients was recently reported by Stewart et al, 98 who showed an abundance of Aspergillus and Penicillium taxa in CDI patients, which were negatively correlated with the presence of some bacterial taxa; Oscillospira , Comamonadaceae , Microbacteriaceae and Cytophagaceae . Taken together, it seems that bilateral interaction between fungi–bacteria could be an important factor involving in the pathophysiology of CDI.…”

Section: Correlation Between the Gut Mycobiome And The Gut Bacteriasupporting

confidence: 79%

Gut mycobiome: The probable determinative role of fungi in IBD patients

Beheshti-Maal

Shahrokh

Ansari

et al. 2021

Mycoses

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Inflammatory bowel disease (IBD) is a multi‐factorial autoimmune disorder that its causative agents are unknown. The gut microbiota comprises of bacteria, viruses, fungi and protozoa that its role in IBD has remained controversially. Bacteria constitute more than 99% of the gut microbiota composition, and the main core of the gut microbiota is composed from Bacteroidetes and Firmicutes. The gut microbiota plays an important role in training, development and haemostasis of the immune responses during the life. Fungi compose a very small portion of gut microbiota, but play determinative roles in homeostasis of the gut bacterial composition and the mucosal immune responses. An interkingdom correlation between bacteria and fungi has been suggested. For example, the presence of Salmonella enterica serovar Typhimurium reduces the viability and colonisation of C albicans. Alterations in the composition and function of the gut microbiota, which is known as dysbiosis, are a usual event in patients who suffer from IBD. Although the main reason for this alteration is not clear, the interaction between gut bacteria and gut fungi seems to be an important subject in IBD patients. This review covers new findings on the interaction between fungi and bacteria and the role of fungi in the pathophysiology of IBD.

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Section: Correlation Between the Gut Mycobiome And The Gut Bacteriasupporting

confidence: 79%

Gut mycobiome: The probable determinative role of fungi in IBD patients

Beheshti-Maal

Shahrokh

Ansari

et al. 2021

Mycoses

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“…The microbiota is composed of viruses, fungi, and parasites in addition to bacteria, and these nonbacterial members can also vary across sources of mice ( 55 , 56 ). While our study focused solely on the bacterial portion, viruses and fungi have also begun to be implicated in the context of CDIs or fecal microbiota transplantation (FMT) treatments for recurrent CDIs ( 34 , 57 – 60 ). Beyond community composition, the metabolic function of the microbiota also has a CDI signature ( 19 , 46 , 61 , 62 ) and can vary across mice from different sources ( 63 ).…”

Section: Discussionmentioning

confidence: 99%

The Initial Gut Microbiota and Response to Antibiotic Perturbation Influence Clostridioides difficile Clearance in Mice

Tomkovich

Stough

Bishop

et al. 2020

mSphere

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The gut microbiota has a key role in determining susceptibility to Clostridioides difficile infections (CDIs). However, much of the mechanistic work examining CDIs in mouse models uses animals obtained from a single source. We treated mice from 6 sources (2 University of Michigan colonies and 4 commercial vendors) with clindamycin, followed by a C. difficile challenge, and then measured C. difficile colonization levels throughout the infection. The microbiota were profiled via 16S rRNA gene sequencing to examine the variation across sources and alterations due to clindamycin treatment and C. difficile challenge. While all mice were colonized 1 day postinfection, variation emerged from days 3 to 7 postinfection with animals from some sources colonized with C. difficile for longer and at higher levels. We identified bacteria that varied in relative abundance across sources and throughout the experiment. Some bacteria were consistently impacted by clindamycin treatment in all sources of mice, including Lachnospiraceae, Ruminococcaceae, and Enterobacteriaceae. To identify bacteria that were most important to colonization regardless of the source, we created logistic regression models that successfully classified mice based on whether they cleared C. difficile by 7 days postinfection using community composition data at baseline, post-clindamycin treatment, and 1 day postinfection. With these models, we identified 4 bacterial taxa that were predictive of whether C. difficile cleared. They varied across sources (Bacteroides) or were altered by clindamycin (Porphyromonadaceae) or both (Enterobacteriaceae and Enterococcus). Allowing for microbiota variation across sources better emulates human interindividual variation and can help identify bacterial drivers of phenotypic variation in the context of CDIs. IMPORTANCE Clostridioides difficile is a leading nosocomial infection. Although perturbation to the gut microbiota is an established risk, there is variation in who becomes asymptomatically colonized, develops an infection, or has adverse infection outcomes. Mouse models of C. difficile infection (CDI) are widely used to answer a variety of C. difficile pathogenesis questions. However, the interindividual variation between mice from the same breeding facility is less than what is observed in humans. Therefore, we challenged mice from 6 different breeding colonies with C. difficile. We found that the starting microbial community structures and C. difficile persistence varied by the source of mice. Interestingly, a subset of the bacteria that varied across sources were associated with how long C. difficile was able to colonize. By increasing the interindividual diversity of the starting communities, we were able to better model human diversity. This provided a more nuanced perspective of C. difficile pathogenesis.

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“…The role of eukaryotes in the development of CDI has been addressed in only a few investigations in which the involvement of fungi was emphasized 13 , 14 . Among the main findings was an increase in the relative abundance of fungi of the genus Penicillium in patients with CDI compared with patients without CDI 15 , as well as a relationship between C. albicans and failures in fecal transplant treatment 16 .…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota composition in health-care facility-and community-onset diarrheic patients with Clostridioides difficile infection

Herrera

Vega

Patarroyo

et al. 2021

Sci Rep

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The role of gut microbiota in the establishment and development of Clostridioides difficile infection (CDI) has been widely discussed. Studies showed the impact of CDI on bacterial communities and the importance of some genera and species in recovering from and preventing infection. However, most studies have overlooked important components of the intestinal ecosystem, such as eukaryotes and archaea. We investigated the bacterial, archaea, and eukaryotic intestinal microbiota of patients with health-care-facility- or community-onset (HCFO and CO, respectively) diarrhea who were positive or negative for CDI. The CDI-positive groups (CO/+, HCFO/+) showed an increase in microorganisms belonging to Bacteroidetes, Firmicutes, Proteobacteria, Ascomycota, and Opalinata compared with the CDI-negative groups (CO/−, HCFO/−). Patients with intrahospital-acquired diarrhea (HCFO/+, HCFO/−) showed a marked decrease in bacteria beneficial to the intestine, and there was evidence of increased Archaea and Candida and Malassezia species compared with the CO groups (CO/+, CO/−). Characteristic microbiota biomarkers were established for each group. Finally, correlations between bacteria and eukaryotes indicated interactions among the different kingdoms making up the intestinal ecosystem. We showed the impact of CDI on microbiota and how it varies with where the infection is acquired, being intrahospital-acquired diarrhea one of the most influential factors in the modulation of bacterial, archaea, and eukaryotic populations. We also highlight interactions between the different kingdoms of the intestinal ecosystem, which need to be evaluated to improve our understanding of CDI pathophysiology.

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Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in Clostridioides difficile Infection

Cited by 37 publications

References 38 publications

Gut mycobiome: The probable determinative role of fungi in IBD patients

Gut mycobiome: The probable determinative role of fungi in IBD patients

The Initial Gut Microbiota and Response to Antibiotic Perturbation Influence Clostridioides difficile Clearance in Mice

Gut microbiota composition in health-care facility-and community-onset diarrheic patients with Clostridioides difficile infection

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