RESUMO
The development of biomarkers for inflammatory bowel disease (IBD) diagnosis would be relevant in a generalized context. However, intercontinental investigation on these microbial biomarkers remains scarce. We examined taxonomic microbiome variations in IBD using published DNA shotgun metagenomic data. For this purpose, we used sequenced data from our previous Spanish Crohn's disease (CD) and ulcerative colitis (UC) cohort, downloaded sequence data from a Chinese CD cohort, and downloaded taxonomic and functional profiling tables from a USA CD and UC cohort. At the global level, geographical location and disease phenotype were the main explanatory covariates of microbiome variations. In healthy controls (HC) and UC, geography turned out to be the most important factor, while disease intestinal location was the most important one in CD. Disease severity correlated with lower alpha-diversity in UC but not in CD. Across geography, alpha-diversity was significantly different independently of health status, except for CD. Despite recruitment from different countries and with different disease severity scores, CD patients may harbor a very similar microbial taxonomic profile. Our study pointed out that geographic location, disease activity status, and other environmental factors are important contributing factors in microbiota changes in IBD. We therefore strongly recommend taking these factors into consideration for future IBD studies to obtain globally valid and reproducible biomarkers.
Assuntos
Colite Ulcerativa , Doença de Crohn , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Biomarcadores , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Fezes , Microbioma Gastrointestinal/genética , HumanosRESUMO
BACKGROUND AND AIMS: Intestinal microbiota dysbiosis is implicated in Crohn's disease [CD] and may play an important role in triggering postoperative disease recurrence [POR]. We prospectively studied faecal and mucosal microbial recolonisation following ileocaecal resection to identify the predictive value of recurrence-related microbiota. METHODS: Mucosal and/or faecal samples from 121 CD patients undergoing ileocaecal resection were collected at predefined time points before and after surgery. Ileal biopsies were collected from 39 healthy controls. POR was defined by a Rutgeerts scoreâ ≥i2b. The microbiota was evaluated by 16S rRNA sequencing. Prediction analysis was performed using C5.0 and Random Forest algorithms. RESULTS: The mucosa-associated microbiota in CD patients was characterised by a depletion of butyrate-producing species (false discovery rate [FDR]â <0.01) and enrichment of Proteobacteria [FDRâ =â 0.009] and Akkermansia spp. [FDRâ =â 0.02]. Following resection, a mucosal enrichment of Lachnospiraceae [FDRâ <0.001] was seen in all patients but in POR patients, also Fusobacteriaceae [FDRâ <0.001] increased compared with baseline. Patients without POR showed a decrease of Streptococcaceae [FDRâ =â 0.003] and Actinomycineae [FDRâ =â 0.06]. The mucosa-associated microbiota profile had good discriminative power to predict POR, and was superior to clinical risk factors. At Month 6, patients experiencing POR had a higher abundance of taxa belonging to Negativicutes [FDRâ =â 0.04] and Fusobacteria [FDRâ =â 0.04] compared with patients without POR. CONCLUSIONS: Microbiota recolonisation after ileocaecal resection is different between recurrence and non-recurrence patients, with Fusobacteria as the most prominent player driving early POR. These bacteria involved in the early recolonisation and POR represent a promising therapeutic strategy in the prevention of disease recurrence.