Oral Candida administration in a Clostridium difficile mouse model worsens disease severity but is attenuated by Bifidobacterium

Panpetch, Wimonrat; Somboonna, Naraporn; Palasuk, Matanee; Hiengrach, Pratsanee; Finkelman, Malcolm; Tumwasorn, Somying; Leelahavanichkul, Asada

doi:10.1371/journal.pone.0210798

Cited by 59 publications

(59 citation statements)

References 40 publications

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“…Severity and outcome of CDI could finally be influenced by communities of gut inhabitants (or transient passengers) not addressed in the present study, such as gut fungi. Recently, it has been shown that oral Candida albicans administration in a C. difficile mouse model worsens disease severity, exacerbating several markers used to characterize the severity of CDI (i.e., mortality rate, weight loss, gut leakage, and serum and intestinal tissue cytokines), without increased fecal C. difficile or bacteremia detection [32].…”

Section: Discussionmentioning

confidence: 99%

Microbiota in Clostridioides difficile-Associated Diarrhea: Comparison in Recurrent and Non-Recurrent Infections

et al. 2020

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Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea, especially in hospitalized elderly patients, representing a global public health concern. Clinical presentations vary from mild diarrhea to severe pseudomembranous colitis that may progress to toxic megacolon or intestinal perforation. Antibiotic therapy is recognized as a risk factor and exacerbates dysbiosis of the intestinal microbiota, whose role in CDI is increasingly acknowledged. A clinically challenging complication is the development of recurrent disease (rCDI). In this study, using amplicon metagenomics, we compared the fecal microbiota of CDI and rCDI patients (sampled at initial and recurrent episode) and of non-infected controls. We also investigated whether CDI severity relates to specific microbiota compositions. rCDI patients showed a significantly decreased bacterial diversity as compared to controls (p < 0.01). The taxonomic composition presented significant shifts: both CDI and rCDI patients displayed significantly increased frequencies of Firmicutes, Peptostreptococcaceae, Clostridium XI, Clostridium XVIII, and Enterococcaceae. Porphyromonadaceae and, within it, Parabacteroides displayed opposite behaviors in CDI and rCDI, appearing discriminant between the two. Finally, the second episode of rCDI was characterized by significant shifts of unclassified Clostridiales, Escherichia/Shigella and Veillonella. No peculiar taxa composition correlated with the severity of infection, likely reflecting the role of host-related factors in determining severity.

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Section: Discussionmentioning

confidence: 99%

Microbiota in Clostridioides difficile-Associated Diarrhea: Comparison in Recurrent and Non-Recurrent Infections

et al. 2020

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“…In vitro models C. albicans coculture promotes C. difficile and C. perfringens growth in aerobic conditions [63] C. difficile mouse model Oral Candida administration worsens C. difficile severity [64] Antagonistic In vitro models p-cresol, produced by C. difficile, inhibits hyphal formation and virulence of C. albicans [63] C. difficile mouse model C. albicans reduces C. difficile growth and C. difficile-related mortality, which appears dependent on the alterations that Candida induces on the gut bacteriome composition [40] https://doi.org/10.1371/journal.ppat.1008353.t001…”

Section: Synergymentioning

confidence: 99%

The gut mycobiome: The overlooked constituent of clinical outcomes and treatment complications in patients with cancer and other immunosuppressive conditions

Galloway-Peña

Kontoyiannis

2020

PLoS Pathog

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Extensive efforts have focused on investigating the contributions of the intestinal microbiome to health and disease, including immunomodulation [1, 2]. While the term "microbiome" technically refers to microorganisms including bacteria, fungi, viruses, protozoa, and parasites, the majority of studies focus on the bacteriome [3]. Although the bacteriome constitutes >99% of the microbiome [4] (which is potentially the reason most studies focus on the bacteriome), it is irrefutable that the commensal fungi, or the "mycobiome," alongside the other microorganisms, coexist and interact ways that can be beneficial or detrimental to the host [5-7]. Emerging research has focused on how the bacteriome relates to gastrointestinal (GI) disorders, cancer therapy-related toxicities, and stem-cell transplantation outcomes; including correlations with infection, graft-versus-host disease (GvHD), tumorigenesis, cancer relapse, and mortality [8-11]. Thus far, there has been a lack of dedicated research focusing on the influence of mycobiome-associated immunomodulation in patients with cancer and other states of immunosuppression. Herein, by focusing on the gut ecosystem, we discuss the role of fungi in various patient populations, the importance of bacterial-fungal dysbiosis, and offer ideas for future investigations regarding the role of mycobiome. Current implications of gut fungi in patients with cancer or critical illness Fungal diversity and density are low in healthy subjects [7], although the factors for colonization resistance against fungi in the gut are inadequately understood. It has been long known that commensal bacteria limit fungal colonization via activation of mucosal innate immunity by bacterial derived metabolites [12], while antibacterial agents can predispose individuals to Candida albicans colonization and infections [13]. For example, antibiotic-induced dysbiosis of intestinal microbes, such as Bacteriodes spp., was linked to a reduction in the cathelicidin antimicrobial peptide (CRAMP), which resulted in the outgrowth of intestinal Candida spp. [12]. Recently, it was found that an antibiotic-induced reduction in the levels of bacterial derived short-chain fatty acids (SCFAs) in the cecum enhanced GI colonization of C. albicans [14]. Antibiotics, however, are not the only factor that can potentially result in increased fungal burden in the gut. In addition to the known effects of proton pump inhibitors (PPIs) as

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“…Although these studies suggest a protective role for C. albicans during CDI, other groups have reported opposite effects. Panpetch and co-workers recently reported that the presence of C. albicans during CDI increased virulence in a murine model [67]. In these studies, the authors introduced C. albicans one day before C. difficile infection and observed disease exacerbation presumably due to increased inflammatory responses [67].…”

Section: Discussionmentioning

confidence: 99%

“…Panpetch and co-workers recently reported that the presence of C. albicans during CDI increased virulence in a murine model [67]. In these studies, the authors introduced C. albicans one day before C. difficile infection and observed disease exacerbation presumably due to increased inflammatory responses [67]. The conflicting results from these murine studies are likely due to the timing of Candida acquisition.…”

Section: Discussionmentioning

confidence: 99%

Lipid Species in the GI Tract are Increased by the Commensal Fungus Candida albicans and Decrease the Virulence of Clostridioides difficile

Romo

Markey

Kumamoto

2020

JoF

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Prior antibiotic treatment is a risk factor for Clostridioides difficile infection (CDI); the commensal gut microbiota plays a key role in determining host susceptibility to the disease. Previous studies demonstrate that the pre-colonization of mice with a commensal fungus, Candida albicans, protects against a lethal challenge with C. difficile spores. The results reported here demonstrate that the cecum contents of antibiotic-treated mice with C. albicans colonization contained different levels of several lipid species, including non-esterified, unsaturated long-chain fatty acids compared to non-C. albicans-colonized mice. Mice fed olive oil for one week and challenged with C. difficile spores showed enhanced survival compared to PBS-fed mice. The amount of olive oil administered was not sufficient to cause weight gain or to result in significant changes to the bacterial microbiota, in contrast to the effects of a high-fat diet. Furthermore, the direct exposure of C. difficile bacteria in laboratory culture to the unsaturated fatty acid oleic acid, the major fatty acid found in olive oil, reduced the transcription of genes encoding the toxins and reduced the survival of bacteria in the post-exponential phase. Therefore, the effects of C. albicans on the metabolite milieu contributed to the attenuation of C. difficile virulence.

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Oral Candida administration in a Clostridium difficile mouse model worsens disease severity but is attenuated by Bifidobacterium

Cited by 59 publications

References 40 publications

Microbiota in Clostridioides difficile-Associated Diarrhea: Comparison in Recurrent and Non-Recurrent Infections

Microbiota in Clostridioides difficile-Associated Diarrhea: Comparison in Recurrent and Non-Recurrent Infections

The gut mycobiome: The overlooked constituent of clinical outcomes and treatment complications in patients with cancer and other immunosuppressive conditions

Lipid Species in the GI Tract are Increased by the Commensal Fungus Candida albicans and Decrease the Virulence of Clostridioides difficile

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