Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn’s Disease

Abstract

Crohn’s disease (CD) results from a complex interplay between host genetic factors and endogenous microbial communities. In the current study, we used Ion Torrent sequencing to characterize the gut bacterial microbiota (bacteriome) and fungal community (mycobiome) in patients with CD and their nondiseased first-degree relatives (NCDR) in 9 familial clusters living in northern France-Belgium and in healthy individuals from 4 families living in the same area (non-CD unrelated [NCDU]). Principal component, diversity, and abundance analyses were conducted, and CD-associated inter- and intrakingdom microbial correlations were determined. Significant microbial interactions were identified and validated using single- and mixed-species biofilms. CD and NCDR groups clustered together in the mycobiome but not in the bacteriome. Microbiotas of familial (CD and NCDR) samples were distinct from those of nonfamilial (NCDU) samples. The abundance of Serratia marcescens and Escherichia coli was elevated in CD patients, while that of beneficial bacteria was decreased. The abundance of the fungus Candida tropicalis was significantly higher in CD than in NCDR (P = 0.003) samples and positively correlated with levels of anti-Saccharomyces cerevisiae antibodies (ASCA). The abundance of C. tropicalis was positively correlated with S. marcescens and E. coli, suggesting that these organisms interact in the gut. The mass and thickness of triple-species (C. tropicalis plus S. marcescens plus E. coli) biofilm were significantly greater than those of single- and double-species biofilms. C. tropicalis biofilms comprised blastospores, while double- and triple-species biofilms were enriched in hyphae. S. marcescens used fimbriae to coaggregate or attach with C. tropicalis/E. coli, while E. coli was closely apposed with C. tropicalis. Specific interkingdom microbial interactions may be key determinants in CD.

Fungal interactions with the human host: exploring the spectrum of symbiosis

“…Shifts in fungal populations leading to dysbiosis are associated with various diseases [35,36]. In this situation, members of the mycobiome transition from commensal to parasitic symbionts.…”

Host–microbe interactions: commensal fungi in the gut

“…as well as Cladosporium , Wallemia , and Malassezia spp. [4,7–15]. Some reports also include robust detection of fungi such as Phoma , Alternaria , Sclerotinia and others which are primarily plant pathogens and are likely to be carried by food or other environmental sources.…”

“…The causes of IBD remain elusive, although data suggest that variations in environmental factors, host genetics, and gut microbiota, all contribute to susceptibility to disease. As the mycobiome has gained attention for its role in promoting both health and disease, several studies have begun to investigate whether there is evidence of fungal dysbiosis or altered immune responses to fungi in IBD patients [9,14,15,26,27]. …”

The mycobiome of the human urinary tract: potential roles for fungi in urology

“…Alterations in the mycobiome occurring in the absence of classical infections have been implicated in a wide range of diseases, such as chronic hepatitis B virus (HBV) hepatitis (25), atopic dermatitis (71), dandruff (72), IBD (73)(74)(75), cystic fibrosis (24), allergy/atopy (64), asthma (76), and psoriasis (77,78). There is no obvious pattern of fungal alterations in these diseases; pathology can be associated with either a decreased or increased diversity from that seen in the healthy state.…”