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Recent population-based1–4 and clinical studies5 have identified a range of factors associated with human gut microbiome variation. Murine quantitative trait loci6, human twin studies7 and microbiome genome-wide association studies1,3,8–12 have provided evidence for genetic contributions to microbiome composition. Despite this, there is still poor overlap in genetic association across human studies. Using appropriate taxon-specific models, along with support from independent cohorts, we show an association between human host genotype and gut microbiome variation. We also suggest that interpretation of applied analyses using genetic associations is complicated by the probable overlap between genetic contributions and heritable components of host environment. Using faecal 16S ribosomal RNA gene sequences and host genotype data from the Flemish Gut Flora Project (n = 2,223) and two German cohorts (FoCus, n = 950; PopGen, n = 717), we identify genetic associations involving multiple microbial traits. Two of these associations achieved a study-level threshold of P = 1.57 × 10−10; an association between Ruminococcus and rs150018970 near RAPGEF1 on chromosome 9, and between Coprococcus and rs561177583 within LINC01787 on chromosome 1. Exploratory analyses were undertaken using 11 other genome-wide associations with strong evidence for association (P

ObjectiveHuman gut microbiome studies are mainly bacteria- and archaea-oriented, overlooking the presence of single-cell eukaryotes such as Blastocystis, an enteric stramenopiles with worldwide distribution. Here, we surveyed the prevalence and subtype variation of Blastocystis in faecal samples collected as part of the Flemish Gut Flora Project (FGFP), a Western population cohort. We assessed potential links between Blastocystis subtypes and identified microbiota–host covariates and quantified microbiota differentiation relative to subtype abundances.DesignWe profiled stool samples from 616 healthy individuals from the FGFP cohort as well as 107 patients with IBD using amplicon sequencing targeting the V4 variable region of the 16S rRNA and 18S rRNA genes. We evaluated associations of Blastocystis, and their subtypes, with host parameters, diversity and composition of bacterial and archaeal communities.ResultsBlastocystis prevalence in the non-clinical population cohort was 30% compared with 4% among Flemish patients with IBD. Within the FGFP cohort, out of 69 previously identified gut microbiota covariates, only age was associated with Blastocystis subtype carrier status. In contrast, a strong association between microbiota community composition and Blastocystis subtypes was observed, with effect sizes larger than that of host covariates. Microbial richness and diversity were linked to both Blastocystis prevalence and subtype variation. All Blastocystis subtypes detected in this cohort were found to be less prevalent in Bacteroides enterotyped samples. Interestingly, Blastocystis subtypes 3 and 4 were inversely correlated with Akkermansia, suggesting differential associations of subtypes with host health.ConclusionsThese results emphasise the role of Blastocystis as a common constituent of the healthy gut microbiota. We show its prevalence is reduced in patients with active IBD and demonstrate that subtype characterisation is essential for assessing the relationship between Blastocystis, microbiota profile and host health. These findings have direct clinical applications, especially in donor selection for faecal transplantation.

Objective Human gut microbiome studies are mainly bacteria- and archaea-oriented, overlooking the presence of single-cell eukaryotes such as Blastocystis, an enteric stramenopiles with worldwide distribution. Here, we surveyed the prevalence and subtype variation of Blastocystis in faecal samples collected as part of the Flemish Gut Flora Project (FGFP), a Western population cohort. We assessed potential links between Blastocystis subtypes and identified microbiota–host covariates and quantified microbiota differentiation relative to subtype abundances. Design We profiled stool samples from 616 healthy individuals from the FGFP cohort as well as 107 patients with IBD using amplicon sequencing targeting the V4 variable region of the 16S rRNA and 18S rRNA genes. We evaluated associations of Blastocystis, and their subtypes, with host parameters, diversity and composition of bacterial and archaeal communities. Results Blastocystis prevalence in the non-clinical population cohort was 30% compared with 4% among Flemish patients with IBD. Within the FGFP cohort, out of 69 previously identified gut microbiota covariates, only age was associated with Blastocystis subtype carrier status. In contrast, a strong association between microbiota community composition and Blastocystis subtypes was observed, with effect sizes larger than that of host covariates. Microbial richness and diversity were linked to both Blastocystis prevalence and subtype variation. All Blastocystis subtypes detected in this cohort were found to be less prevalent in Bacteroides enterotyped samples. Interestingly, Blastocystis subtypes 3 and 4 were inversely correlated with Akkermansia, suggesting differential associations of subtypes with host health. Conclusions These results emphasise the role of Blastocystis as a common constituent of the healthy gut microbiota. We show its prevalence is reduced in patients with active IBD and demonstrate that subtype characterisation is essential for assessing the relationship between Blastocystis, microbiota profile and host health. These findings have direct clinical applications, especially in donor selection for faecal transplantation.

“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