Long-term instability of the intestinal microbiome is associated with metabolic liver disease, low microbiota diversity, diabetes mellitus and impaired exocrine pancreatic function

Abstract

ObjectiveThe 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.DesignA 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.ResultsThe 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.ConclusionThis 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.

Differences in the Concentration of the Fecal Neurotransmitters GABA and Glutamate Are Associated with Microbial Composition among Healthy Human Subjects

“…The highly diverse microbiome is thought to be advantageous for maintenance of the microbial ecosystem. Reduction in alpha diversity was reported to have an association with unhealthy conditions and specific diseases [ 36 ]. Nonetheless, the high abundance of beneficial bacteria such as bifidobacteria in cases of low alpha diversity is often a step forward to restore the microbial diversity [ 37 ].…”

Early life gut microbiome dynamics mediate maternal effects on infant growth in vervet monkeys

“…Consistent with previous studies in humans and rhesus macaques but opposite a recent study in chimpanzees [51,52], alpha diversity of the vervet monkey infant gut microbiome was lowest during early life, converging rapidly toward maternal gut microbiome levels by 4 months old. Although a less diverse microbiome during adulthood can indicate microbiome dysbiosis [53,54], reduced diversity during development may instead reflect specialization of the gut microbiome for specific functions. Indeed, the infant gut microbiome of breastfed human infants is less diverse than formula-fed infants and houses more microbial taxa involved in milk glycan metabolism [55][56][57].…”

From taxonomy to metabolic output: what factors define gut microbiome health?

“… 77–79 Perhaps unsurprisingly, temporal stability and gut microbial α-diversity tend to be related. 80 Shannon diversity was positively associated with gut microbiome stability (assessed using Weighted UniFrac) in healthy adults when the microbiome was sampled weekly across the course of three months. 81 Similarly, very low gut microbial α-diversity in a cohort of older individuals corresponded to higher levels of ß-diversity instability when measured up to six months apart.…”

“…For example, both fatty liver disease and type II diabetes were associated with higher gut ß-diversity instability (Bray-Curtis dissimilarity) in a cohort of German adults when sampled across a span of five years. 80 Using 16S rRNA gene sequencing, Halfvarson et al . 83 demonstrated that patients suffering from IBD (UC and CD) had higher levels of temporal instability compared to healthy controls.…”