Gut microbiome alterations in Alzheimer’s disease (2017)
https://www.nature.com/articles/s41598-017-13601-yIn our study, the phylum Firmicutes as a whole, as well as several families, genera, and 61 OTUs classified within Firmicutes were decreased in the AD group. A reduction in Firmicutes has been reported in the microbiome of individuals with type 2 diabetes25 as well as obesity29 (although others have reported increased Firmicutes in obesity24,30). Notably, diabetes and insulin resistance increase the risk of developing AD31,32,33. We have recently reported that insulin resistance is associated with decreased cerebral glucose metabolism and increased amyloid deposition in asymptomatic middle-aged adults enriched for risk of AD34,35. Thus, a potential mechanism by which microbial alterations in the gut may influence AD pathology is through promoting the development of insulin resistance and diabetes. While AD and Control groups did not differ with respect to diabetes prevalence (Table 1), sub-clinical differences in insulin or glucose metabolism cannot be ruled out. Further investigation will be needed to explore the relationship between microbiota and insulin resistance in AD.
In participants with AD, we observed an increase in the phylum Bacteroidetes, which was reflected by increased Bacteroidaceae at the family level, and increased Bacteroides at the OTU and genus level. The phylum Bacteroidetes encompasses a diverse and abundant group of gram-negative commensal bacteria in the gut36, including the genus Bacteroides, which has been detected at higher levels in the gut of individuals with type 2 diabetes25 and in patients with Parkinson’s disease13, a neurodegenerative disorder. The major outer membrane component of gram-negative bacteria is lipopolysaccharide (LPS), which is capable of triggering systemic inflammation and the release of pro-inflammatory cytokines after translocation from the gut to systemic circulation37. Additionally, in vitro and in vivo studies have demonstrated an association between bacterial endotoxins (e.g. LPS) and AD pathology...
Additionally, compared to control participants, AD participants in our study exhibited decreased Actinobacteria. These differences were mostly driven by changes in Bifidobacterium. Actinobacteria, particularly members of the Bifidobacterium genus, are an important bacterial inhabitant of the human gut across the lifespan, and their beneficial health effects have been well-documented46,47. In particular, certain species of Bifidobacterium are associated with anti-inflammatory properties and decreased intestinal permeability48. Additionally, supplementation with Bifidobacterium has been shown to decrease LPS levels in the intestine and improve gut mucosal barrier properties in mice49,50. Interestingly, in germ-free mice colonized with human gut microbiota, increased levels of Bifidobacterium are associated with decreased bacterial translocation to systemic circulation, while increased levels of Bacteroides have been shown to increase bacterial translocation51. Considering our present findings, increased Bacteroides and decreased Bifidobacterium in AD participants may represent a gut microbial phenotype with particular propensity for translocation of pro-inflammatory bacterial components. Furthermore, several Bifidobacterium species are widely used as probiotics. A small study of probiotics that included Bifidobacterium demonstrated a change in Mini-Mental State Examination scores after a 12-week intervention among participants with severe dementia52. Taken together with the decreased abundance of Bifidobacterium in AD participants observed in our study, larger trials may be warranted, particularly in earlier disease stages.
