The fecal microbiome as predictor of diagnoses prior to their clinical onset

Perturbations in the gut microbiome have been associated with numerous common diseases, including inflammatory bowel disease (IBD), diabetes and obesity, carcinogenic and autoimmune disorders, and neuropsychiatric disorders (1-3). The discovery of an altered gut microbiome composition in these diseases has led to increased research efforts in exploring the potential of the gut microbiome in these diseases as diagnostic tool, predictor of treatment response and as therapeutic tool. 
Most of the research efforts that have explored the gut microbiome thus far, however, are based on cohorts including patients with established disease. This hampers the discovery of whether these gut microbiome perturbations precede the onset of the aforementioned diseases, or are solely present once disease is established, i.e. are its’ consequence. Defining whether these changes occur prior to or after established disease could aid in characterizing the role of the gut microbiome in the pathogenesis of the onset and disease course. Up until now, it has proven to be very challenging to define a human cohort likely to develop a disease within a short period of time, in order to prospectively collect fecal samples prior to and during the onset of disease. 
Between 2014-2016, fecal samples of ~8600 individuals of the general population (Lifelines project ID OV17_0388) were collected and sequenced using whole genome metagenomic shotgun sequencing. Linking the already available fecal metagenomes of the DAG3 cohort (Project ID OV17_0388) to PA confirmed diagnoses ((pre)malignant and autoimmune disorders) documented in the PALGA database (2017-127, 2020-208, 2020-209) – possibly documented post-feces – offers a unique possible pre-diagnosis and pre-therapeutic cohort, to distinguish cause and consequence of the gut microbiome in numerous common diseases.