Abundant data have incriminated intestinal bacteria in the initiation and amplification stages of inflammatory bowel diseases. However, the precise role of intestinal bacteria remains elusive. One theory has suggested a breakdown in the balance between putative species of “protective” versus “harmful” intestinal bacteria—this concept has been termed “dysbiosis”. Arguments in support of this concept are discussed.

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. IMPORTANCE Here, we characterized the gut bacterial microbiota (bacteriome) and fungal community (mycobiome) in multiplex families with CD and healthy relatives and defined the microbial interactions leading to dysbiosis in CD. We identified fungal ( Candida tropicalis ) and bacterial ( Serratia marcescens and Escherichia coli ) species that are associated with CD dysbiosis. Additionally, we found that the level of anti- Saccharomyces cerevisiae antibodies (ASCA; a known CD biomarker) was associated with the abundance of C. tropicalis . We also identified positive interkingdom correlations between C. tropicalis , E. coli , and S. marcescens in CD patients and validated these correlations using in vitro biofilms. These results provide insight into the roles of bacteria and fungi in CD and may lead to the development of novel treatment approaches and diagnostic assays.

Background: Nondigestible carbohydrates (NDCHs) are fermented in the colon, where they can selectively promote the growth of bifidobacteria. Objective: Our aim was to determine the bifidogenic potential of different NDCHs used in human diets. Design: Two hundred healthy volunteers participated in this double-blind study. During phase 1 (screening), 64 volunteers were randomly assigned to 8 groups of 8 subjects each; for 7 d, they ingested 10 g/d of 1 of the 7 NDCHs tested or of the placebo. During phase 2 (dose-response study), 136 volunteers were randomly assigned to 4 groups of 32 subjects who received 2.5, 5.0, 7.5, or 10 g/d, respectively (8 subjects/dose), of one of the NDCHs that were proven to be bifidogenic during phase 1 and a fifth group of 8 subjects (control subjects) who received the placebo. Stools were recovered before and after NDCH consumption. Results: In phase 1, 4 NDCHs were found to be bifidogenic: short-chain fructooligosaccharides (P = 0.008), soybean oligosaccharides (P = 0.006), galactooligosaccharides (P < 0.0001), and type III resistant starch (P = 0.02); lactulose, long-chain inulin, and isomaltooligosaccharides were not bifidogenic. In phase 2, the effects of 7-d treatment on bifidobacteria concentrations were found to differ significantly among the 4 NDCHs (P = 0.009 for time × treatment interaction). However, no significant differences were found among doses, and there was no significant dose × time interaction. A low baseline bifidobacteria count was significantly associated with the bifidogenic response to treatment (P < 0.001). Conclusion: This study showed the different bifidogenic properties among the substrates and underlined the importance of taking into account the baseline bifidobacteria counts when evaluating the effect of the treatment.