Dataset Information

Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease.

ABSTRACT:

Background and aims

Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA].

Methods

Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab.

Results

We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test.

Conclusions

Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.

SUBMITTER: Hurych J

PROVIDER: S-EPMC10821711 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease.

Hurych Jakub J Mascellani Bergo Anna A Lerchova Tereza T Hlinakova Lucie L Kubat Michal M Malcova Hana H Cebecauerova Dita D Schwarz Jan J Karaskova Eva E Hecht Tomas T Vyhnanek Radim R Toukalkova Lenka L Dotlacil Vojtech V Greinerova Katerina K Cizkova Anabela A Horvath Rudolf R Horvath Rudolf R Bronsky Jiri J Havlik Jaroslav J Hradsky Ondrej O Cinek Ondrej O

Journal of Crohn's & colitis 20240101 1

<h4>Background and aims</h4>Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contras ...[more]

PMID: 37527838

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Project description: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. 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.

Dataset Information

Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease.

Background and aims

Methods

Results

Conclusions

Publications

Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease.

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