PT  - JOURNAL ARTICLE
AU  - Fabian Frost
AU  - Tim Kacprowski
AU  - Malte Rühlemann
AU  - Maik Pietzner
AU  - Corinna Bang
AU  - Andre Franke
AU  - Matthias Nauck
AU  - Uwe Völker
AU  - Henry Völzke
AU  - Marcus Dörr
AU  - Jan Baumbach
AU  - Matthias Sendler
AU  - Christian Schulz
AU  - Julia Mayerle
AU  - Frank U Weiss
AU  - Georg Homuth
AU  - Markus M Lerch
TI  - Long-term instability of the intestinal microbiome is associated with metabolic liver disease, low microbiota diversity, diabetes mellitus and impaired exocrine pancreatic function
AID  - 10.1136/gutjnl-2020-322753
DP  - 2021 Mar 01
TA  - Gut
PG  - 522--530
VI  - 70
IP  - 3
4099  - http://gut.bmj.com/content/70/3/522.short
4100  - http://gut.bmj.com/content/70/3/522.full
SO  - Gut2021 Mar 01; 70
AB  - Objective The intestinal microbiome affects the prevalence and pathophysiology of a variety of diseases ranging from inflammation to cancer. A reduced taxonomic or functional diversity of the microbiome was often observed in association with poorer health outcomes or disease in general. Conversely, factors or manifest diseases that determine the long-term stability or instability of the microbiome are largely unknown. We aimed to identify disease-relevant phenotypes associated with faecal microbiota (in-)stability.Design A total of 2564 paired faecal samples from 1282 participants of the population-based Study of Health in Pomerania (SHIP) were collected at a 5-year (median) interval and microbiota profiles determined by 16S rRNA gene sequencing. The changes in faecal microbiota over time were associated with highly standardised and comprehensive phenotypic data to determine factors related to microbiota (in-)stability.Results The overall microbiome landscape remained remarkably stable over time. The greatest microbiome instability was associated with factors contributing to metabolic syndrome such as fatty liver disease and diabetes mellitus. These, in turn, were associated with an increase in facultative pathogens such as Enterobacteriaceae or Escherichia/Shigella. Greatest stability of the microbiome was determined by higher initial alpha diversity, female sex, high household income and preserved exocrine pancreatic function. Participants who newly developed fatty liver disease or diabetes during the 5-year follow-up already displayed significant microbiota changes at study entry when the diseases were absent.Conclusion This study identifies distinct components of metabolic liver disease to be associated with instability of the intestinal microbiome, increased abundance of facultative pathogens and thus greater susceptibility toward dysbiosis-associated diseases.