The role of the gut microbiome in cognitive function and Alzheimer’s disease

Abstract

AbstractBackgroundAlthough the level of evidence suggesting a role of the gut microbiome in the pathogenesis of Alzheimer’s disease (AD) in human and animal models, the evidence in humans is currently based on small studies and cannot determine whether the gut microbiome has changed in AD patients as a cause of consequence of disease. To exclude reverse causation, we have studied the association of the gut microbiome to cognition in 1,184 healthy participants of the Rotterdam Study.MethodFecal microbiome of 1,184 participants from the Rotterdam Study was characterized by 16S rRNA profiling. Cognitive function was assessed using g‐factor. Linear regression was used to associate the gut microbiome to cognitive function adjusting for age, sex, time in mail, storage time, and use of proton pump inhibitors. Further, we performed a systematic literature review to assess the consistency of findings on the association of the gut microbiome in AD and mice. Finally, we assessed the relationship between these microbiota and the general cognitive function.ResultWe found that the relative abundance of the phylum Firmicutes in the gut is associated with a better cognition. The relative abundance of families Lachnospiraceae, Christensenellaceae, Rumininococcaceae and Clostridiaceae explain this association. The relative abundance of Klebsiella, a member of the Enterobacteriaceae family is associated with lower levels of cognition. These findings were independent of potential confounders such as age, BMI, alcohol, and use of medication. Of the 10 associations that we found, 9 could be replicated in the smaller case‐control studies conducted to date in AD.ConclusionThe present study finds that the relative abundance of the phylum Firmicutes in the gut is associated with a better cognition and the relative abundance of Klebsiella with lower levels of cognition. Taken together with studies published previously about AD, we find a relative reduction in phylum Firmicutes and an increased in Klebsiella is associated with lower cognition and dementia.