Gut Microbiome in Alzheimer's Disease: from Mice to Humans

Abstract

Alzheimer's disease (AD) is the most prevalent type of dementia, but its etiopathogenesis is not yet fully understood. Recent preclinical studies and clinical evidence indicate that changes in the gut microbiome could potentially play a role in the accumulation of amyloid beta. However, the relationship between gut dysbiosis and AD is still elusive. In this review, the potential impact of the gut microbiome on AD development and progression is discussed. Pre-clinical and clinical literature exploring changes in gut microbiome composition is assessed, which can contribute to AD pathology including increased amyloid beta deposition and cognitive impairment. The gut-brain axis and the potential involvement of metabolites produced by the gut microbiome in AD are also highlighted. Furthermore, the potential of antibiotics, prebiotics, probiotics, fecal microbiota transplantation, and dietary interventions as complementary therapies for the management of AD is summarized. This review provides valuable insights into potential therapeutic strategies to modulate the gut microbiome in AD.

Keywords: Alzheimer’s disease (AD); diet; fecal microbiota transplantation (FMT); gut microbiome; prebiotics; probiotics..

Fig. (1)

The model of the dynamic alterations of gut microbiota in the HC, AD and MCI patients. With the progression of AD, the results showed that Bacteroidetes, Proteobacteria and Actinobacteria at the phylum level, Enterobacteriaceae at the family level and Bacteroides at the genus level had an increasing trend. Firmicutes at the phylum level, Lachnospiraceae and Ruminococcaceae at family level, and Eubacterium at genus level had a decreasing trend. HC: healthy control; MCI: mild cognitive impairment; AD: Alzheimer's disease; p-Bacteroidetes: phylum Bacteroidetes; g-Bacteroides: genus Bacteroides; p-Firmicutes: phylum Firmicutes; f-Lachnospiraceae: family Lachnospiraceae; f-Ruminococcaceae: family Ruminococcaceae; g-Eubacterium: genus Eubacterium; p-Actinobacteria: phylum Actinobacteria; g-Collinsella: genus Collinsella; p-Proteobacteria, phylum Proteobacteria; f-Enterobacteriaceae: family Enterobacteriaceae.

Fig. (2)

Schematic representation of the standard FMT protocol in humans. (A) The standard of donor selection for FMT. It is recommended that the donors for FMT should be selected from intimate partners, maternal first-degree relatives, family members, or unrelated healthy volunteers. (B) Neurodegenerative pathology in AD. AD is a neurodegenerative disease characterized by progressive memory loss, cognitive impairment, and changes in personality. Pathology includes the presence of misfolded amyloid-beta (Aβ) plaques, deposition of hyperphosphorylated tau as neurofibrillary tangles, loss of neurons and activated microglia and astrocytes. (C) How to administrate FMT. There are several steps to administrate FMT including fecal material preparation, recipient preparation, fecal delivery and monitoring the treatment of response and adverse events after FMT. The fecal sample of AD patients showed increased proinflammatory microbiota and decreased anti-inflammatory microbiota, which can be restored to be normal gut microbial composition after FMT. Abbreviations: FMT: fecal microbiota transplantation; AD: Alzheimer's disease; HC: healthy control; BBB: blood-brain barrier; MMSE: Mini-Mental State Examination; MoCA: Montreal Cognitive Assessment; CDR: Clinical Dementia Rating; AE: adverse events; CMV: cytomegalovirus.