The distinct features of microbial ‘dysbiosis’ of Crohn’s disease do not occur to the same extent in their unaffected, genetically-linked kindred

Abstract

Background/AimsStudying the gut microbiota in unaffected relatives of people with Crohn’s disease (CD) may advance our understanding of the role of bacteria in disease aetiology.MethodsFaecal microbiota composition (16S rRNA gene sequencing), genetic functional capacity (shotgun metagenomics) and faecal short chain fatty acids (SCFA) were compared in unaffected adult relatives of CD children (CDR, n = 17) and adult healthy controls, unrelated to CD patients (HUC, n = 14). The microbiota characteristics of 19 CD children were used as a benchmark of CD ‘dysbiosis’.ResultsThe CDR microbiota was less diverse (p = 0.044) than that of the HUC group. Local contribution of β-diversity analysis showed no difference in community structure between the CDR and HUC groups. Twenty one of 1,243 (1.8%) operational taxonomic units discriminated CDR from HUC. The metagenomic functional capacity (p = 0.207) and SCFA concentration or pattern were similar between CDR and HUC (p>0.05 for all SCFA). None of the KEGG metabolic pathways were different between these two groups. Both of these groups (HUC and CDR) had a higher microbiota α-diversity (CDR, p = 0.026 and HUC, p<0.001) with a community structure (β-diversity) distinct from that of children with CD.ConclusionsWhile some alterations were observed, a distinct microbial ‘dysbiosis’, characteristic of CD patients, was not observed in their unaffected, genetically linked kindred.

VIBRANT: automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences

“…Putative hosts of Crohn's-associated and healthy-associated were estimated using proximity of vConTACT2 protein clustering and BLASTp identity (NCBI non-redundant protein database, assessed October 2019). Two additional read sets from Gevers et al [66] and Ijaz et al [67] were likewise assembled by Pasolli et al VIBRANT (-l 5000 -o 10) was used to predict viruses from 43 metagenomes originating from individuals with Crohn's disease and 21 from healthy individuals (64 total samples). In contrast to the discovery, dataset viral genomes were not dereplicated, and differential abundance was not determined.…”

The microbiome of Crohn’s disease aphthous ulcers

“…Although our Crohn’s disease cohort was small, we were able to demonstrate that dysbiosis is not a feature of aphthous ulcers. Similar sized cohorts of patients have demonstrated dysbiosis in samples obtained from patients with active Crohn’s disease, including a reduction in Faecalibacterium [ 35 , 36 ]. If dysbiosis were a feature of the aphthous ulcer microbiome, we would likely have observed it in a number of our Crohn’s disease patients.…”

“…One study assessed the gut microbiome of unaffected genetically-linked relatives of children with Crohn’s disease. The unaffected relatives had alterations in their gut microbiome in the direction of their relatives with Crohn’s disease, but did not display a distinct dysbiosis [ 36 ]. The findings of this study suggest that dysbiosis develops close to disease onset, or as a consequence of the disease process.…”

VIBRANT: Automated recovery, annotation and curation of microbial viruses, and evaluation of virome function from genomic sequences

“…To validate these aforementioned findings, we applied VIBRANT to two additional metagenomic datasets from cohorts of individuals with Crohn's disease and healthy individuals (validation dataset): 43 from individuals with Crohn's Disease and 21 from healthy individuals [79,80]. VIBRANT identified 3,759 redundant viral genomes from Crohn's-associated metagenomes and 1,444 from healthy-associated metagenomes.…”

“…Putative hosts of Crohn's-associated and healthy-associated was estimated using proximity of vConTACT2 protein clustering and BLASTp identity (NCBI non-redundant protein database, assessed October 2019). Two additional read sets from Gevers et al [80] and Ijaz et al [79] were likewise assembled by Pasolli et al. VIBRANT (-l 5000 -o 10) was used to predict viruses from 43 metagenomes originating from individuals with Crohn's Disease and 21 from healthy individuals (64 total samples).…”