Multi-omics analysis reveals indicator features of microbe-host interactions during Candida albicans colonization and
Huan Zhang1, Daoyuan Song2, Qiulin Luo1
1Department of Clinical Laboratory, The Affiliated Hospital of Yunnan University (The Second People's Hospital of Yunnan Province), Kunming, China.
Introduction:
Candida albicans gastrointestinal (GI) colonization is crucial for the onset of invasive disease. This research encompassed 31 patients diagnosed with Candida spp. bloodstream infections during their admission to a university hospital in China.
Methods:
We explored risk factors associated with C. albicans GI colonization and ensuing translocated infection. Animal models were established via gavage with clinical isolates of C. albicans to induce GI tract colonization and subsequent kidney translocation infection. Our analysis is focused on 16S rRNA gene sequencing, metabolomics of colon contents, and transcriptomics of colon tissues, examining the intestinal barrier, inflammatory responses, and immune cell infiltration.
Results:
This study observed that down-regulation of programmed cell death 1 (PD-1) in colon tissues is likely linked to the progression from C. albicans colonization to translocated infection. Notably, reductions in Dubosiella abundance and Short-chain fatty acids (SCFA) levels, coupled with increases in Mucispirillum and D-erythro-imidazolylglycerol phosphate, were indicator features during the advancement to translocated invasive infection in hosts with rectal colonization by C. albicans and lower serum protein levels.
Conclusion:
Given the similarity in intestinal bacterial communities and metabolome profiles, antifungal treatment may not be necessary for patients with nonpathogenic C. albicans colonization. The reduced expression of PD-1 in colon tissues may contribute to the transition from colonized C. albicans to subsequent translocated infection. The indicator features of decreased Dubosiella abundance and SCFA levels, coupled with increased Mucispirillum and D-erythro-imidazolylglycerol phosphate, are likely linked to the development of translocated invasive infection in hosts colonized rectally by C. albicans with lower serum protein levels.
Importance:
Candida albicans invasive infections pose a significant challenge to contemporary medicine, with mortality rates from such fungal infections remaining high despite antifungal treatment. Gastrointestinal colonization by potential pathogens is a critical precursor to the development of translocated infections. Consequently, there is an increasing demand to identify clinical risk factors, multi-omics profiles, and key indicators to prevent the progression to translocated invasive infections in patients colonized rectally by C. albicans.
Insights
Candida albicans gastrointestinal colonization can lead to invasive infections. Reduced PD-1 expression and specific gut bacteria/metabolite changes indicate this progression, suggesting targeted interventions may be possible.
Area of Science:
- Medical Mycology
- Gastroenterology
- Infectious Diseases
Background:
- Candida albicans gastrointestinal colonization is a precursor to invasive candidiasis.
- Invasive fungal infections have high mortality rates despite antifungal treatments.
- Identifying risk factors for Candida translocation is crucial for prevention.
Purpose of the Study:
- To explore risk factors for Candida albicans gastrointestinal colonization and subsequent translocated infection.
- To identify multi-omics profiles and key indicators of invasive infection progression.
- To investigate the role of the gut microbiome and host immune response in Candida translocation.
Main Methods:
- Analysis of 16S rRNA gene sequencing, metabolomics, and transcriptomics in animal models of Candida GI colonization.
- Examination of intestinal barrier function, inflammatory responses, and immune cell infiltration.
- Correlation of microbial and metabolic changes with host factors like serum protein levels.
Main Results:
- Down-regulation of programmed cell death 1 (PD-1) in colon tissues correlated with progression to translocated infection.
- Reduced Dubosiella abundance and Short-chain fatty acids (SCFA) levels, with increased Mucispirillum and D-erythro-imidazolylglycerol phosphate, were key indicators.
- These changes were associated with rectal colonization by Candida albicans and lower serum protein levels.
Conclusions:
- Reduced PD-1 expression may facilitate Candida albicans transition from colonization to invasive infection.
- Specific microbial and metabolic shifts in the gut are linked to invasive candidiasis development.
- Antifungal therapy might not be necessary for nonpathogenic colonization, highlighting the need for precise diagnostics.
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