The gut microbiome is affected by multiple factors, including genetics. In this study, we assessed the influence of host genetics on microbial species, pathways and gene ontology categories, on the basis of metagenomic sequencing in 1,514 subjects. In a genome-wide analysis, we identified associations of 9 loci with microbial taxonomies and 33 loci with microbial pathways and gene ontology terms at P < 5 × 10. Additionally, in a targeted analysis of regions involved in complex diseases, innate and adaptive immunity, or food preferences, 32 loci were identified at the suggestive level of P < 5 × 10. Most of our reported associations are new, including genome-wide significance for the C-type lectin molecules CLEC4F-CD207 at 2p13.3 and CLEC4A-FAM90A1 at 12p13. We also identified association of a functional LCT SNP with the Bifidobacterium genus (P = 3.45 × 10) and provide evidence of a gene-diet interaction in the regulation of Bifidobacterium abundance. Our results demonstrate the importance of understanding host-microbe interactions to gain better insight into human health.

Further information on research design is available in the Life Sciences Reporting Summary linked to this article. Data availability The LifeLines-DEEP metagenomics sequencing data are available at the European Genome-phenome Archive (EGA), with access code EGAS00001001704. Genotype and phenotype data can be requested from the Lifelines Biobank https://www.lifelines.nl/ researcher/biobank-lifelines/application-process. Summary statistics for metabolic traits were downloaded from MAGIC, GIANT and DIAGRAM websites (see URLs).

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Tryptophan is the precursor of a wide array of metabolites, which are involved in a variety of aspects of human nutrition and metabolism. Accumulating evidence suggests a role of tryptophan metabolites, especially serotonin (5-hydroxytryptamin) in intestinal (patho) physiology, although mechanisms of action are still poorly understood. Alterations of serotonin metabolism may give rise to gastrointestinal dysfunction. Recently, it has been postulated that other metabolites of tryptophan, mostly of the kynurenine pathway, also play a role in regulating gut function. This review analyses the current knowledge of the interrelationship between tryptophan metabolic pathways and summarizes the existing scientific evidence regarding the role of tryptophan metabolites in intestinal function and in the pathogenesis of gastrointestinal diseases.

In our experience, 86.4% of all PCCRCs could be explained by procedural factors, especially missed lesions. Quality improvements in performance of colonoscopy, with special attention to the detection and resection of proximally located flat precursors, have the potential to prevent PCCRCs.

Worldwide, the post-colonoscopy complication rate remained stable or even declined over the past 15 years. The findings of this meta-analysis encourage continued efforts to achieve and maintain safety targets in colonoscopy practice.

The human gut microbiota has now been associated with drug responses and efficacy, while chemical compounds present in these drugs can also impact the gut bacteria. However, drug-microbe interactions are still understudied in the clinical context, where polypharmacy and comorbidities co-occur. Here, we report relations between commonly used drugs and the gut microbiome. We performed metagenomics sequencing of faecal samples from a population cohort and two gastrointestinal disease cohorts. Differences between users and nonusers were analysed per cohort, followed by a meta-analysis. While 19 of 41 drugs are found to be associated with microbial features, when controlling for the use of multiple medications, proton-pump inhibitors, metformin, antibiotics and laxatives show the strongest associations with the microbiome. We here provide evidence for extensive changes in taxonomy, metabolic potential and resistome in relation to commonly used drugs. This paves the way for future studies and has implications for current microbiome studies by demonstrating the need to correct for multiple drug use.

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