“Normal” for the gut microbiota: For the benefit of future clinical studies, it is critical to establish what constitutes a “normal” gut microbiome, if it exists at all. Through fecal samples and questionnaires, Falonyet al.and Zhernakovaet al.targeted general populations in Belgium and the Netherlands, respectively. Gut microbiota composition correlated with a range of factors including diet, use of medication, red blood cell counts, fecal chromogranin A, and stool consistency. The data give some hints for possible biomarkers of normal gut communities.Science, this issue pp.560and565

“Normal” for the gut microbiota: For the benefit of future clinical studies, it is critical to establish what constitutes a “normal” gut microbiome, if it exists at all. Through fecal samples and questionnaires, Falony et al. and Zhernakova et al. targeted general populations in Belgium and the Netherlands, respectively. Gut microbiota composition correlated with a range of factors including diet, use of medication, red blood cell counts, fecal chromogranin A, and stool consistency. The data give some hints for possible biomarkers of normal gut communities. Science , this issue pp. 560 and 565

Objective: Bacteria play an important role in the onset and perpetuation of intestinal inflammation in inflammatory bowel disease (IBD). Unlike in Crohn's disease (CD), in which dysbiosis has been better characterised, in ulcerative colitis (UC), only small cohorts have been studied and showed conflicting data. Therefore, we evaluated in a large cohort if the microbial signature described in CD is also present in UC, and if we could characterise predominant dysbiosis in UC. To assess the functional impact of dysbiosis, we quantified the bacterial metabolites. Design: The predominant microbiota from 127 UC patients and 87 age and sex-matched controls was analysed using denaturing gradient gel electrophoresis (DGGE) analysis. Differences were quantitatively validated using real-time PCR. Metabolites were quantified using gas chromatography–mass spectrometry. Results: Based on DGGE analysis, the microbial signature previously described in CD was not present in UC. Real-time PCR analysis revealed a lower abundance of Roseburia hominis (p<0.0001) and Faecalibacterium prausnitzii (p<0.0001) in UC patients compared to controls. Both species showed an inverse correlation with disease activity. Short-chain fatty acids (SCFA) were reduced in UC patients (p=0.014), but no direct correlation between SCFA and the identified bacteria was found. Conclusions: The composition of the fecal microbiota of UC patients differs from that of healthy individuals: we found a reduction in R hominis and F prausnitzii, both well-known butyrate-producing bacteria of the Firmicutes phylum. These results underscore the importance of dysbiosis in IBD but suggest that different bacterial species contribute to the pathogenesis of UC and CD.

Background and aims A general dysbiosis of the intestinal microbiota has been established in patients with Crohn's disease (CD), but a systematic characterisation of this dysbiosis is lacking. Therefore the composition of the predominant faecal microbiota of patients with CD was studied in comparison with the predominant composition in unaffected controls. Whether dysbiosis is present in relatives of patients CD was also examined. Methods Focusing on families with at least three members affected with CD, faecal samples of 68 patients with CD, 84 of their unaffected relatives and 55 matched controls were subjected to community fingerprinting of the predominant microbiota using denaturing gradient gel electrophoresis (DGGE). To analyse the DGGE profiles, BioNumerics software and non-parametric statistical analyses (SPSS V.17.0) were used. Observed differences in the predominant microbiota were subsequently confirmed and quantified with real-time PCR. Results Five bacterial species characterised dysbiosis in CD, namely a decrease in Dialister invisus (p=0.04), an uncharacterised species of Clostridium cluster XIVa (p=0.03), Faecalibacterium prausnitzii (p<1.3×10⁻⁵) and Bifidobacterium adolescentis (p=5.4×10⁻⁶), and an increase in Ruminococcus gnavus (p=2.1×10⁻⁷). Unaffected relatives of patients with CD had less Collinsella aerofaciens (p=0.004) and a member of the Escherichia coli–Shigella group (p=0.01) and more Ruminococcus torques (p=0.02) in their predominant microbiota as compared with healthy subjects. Conclusion Unaffected relatives of patients with CD have a different composition of their microbiota compared with healthy controls. This dysbiosis is not characterised by lack of butyrate producing-bacteria as observed in CD but suggests a role for microorganisms with mucin degradation capacity.

Objective: The assessment of potentially confounding factors affecting colon microbiota composition is essential to the identification of robust microbiome based disease markers. Here, we investigate the link between gut microbiota variation and stool consistency using Bristol Stool Scale classification, which reflects faecal water content and activity, and is considered a proxy for intestinal colon transit time. Design: Through 16S rDNA Illumina profiling of faecal samples of 53 healthy women, we evaluated associations between microbiome richness, Bacteroidetes:Firmicutes ratio, enterotypes, and genus abundance with self-reported, Bristol Stool Scale-based stool consistency. Each sample’s microbiota growth potential was calculated to test whether transit time acts as a selective force on gut bacterial growth rates. Results: Stool consistency strongly correlates with all known major microbiome markers. It is negatively correlated with species richness, positively associated to the Bacteroidetes:Firmicutes ratio, and linked to Akkermansia and Methanobrevibacter abundance. Enterotypes are distinctly distributed over the BSS-scores. Based on the correlations between microbiota growth potential and stool consistency scores within both enterotypes, we hypothesise that accelerated transit contributes to colon ecosystem differentiation. While shorter transit times can be linked to increased abundance of fast growing species in Ruminococcaceae- Bacteroides samples, hinting to a washout avoidance strategy of faster replication, this trend is absent in Prevotella -enterotyped individuals. Within this enterotype adherence to host tissue therefore appears to be a more likely bacterial strategy to cope with washout. Conclusions: The strength of the associations between stool consistency and species richness, enterotypes and community composition emphasises the crucial importance of stool consistency assessment in gut metagenome-wide association studies.