• Gut - brain communication and effects of microbial short chain fatty on Alzheimer disease
  • Maryam Mazaheri,1,*
    1. Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran


  • Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder and one of the most common causes of forgetfulness in the old ages. Short-chain fatty acids (SCFAs); the main metabolites produced by bacterial fermentation in the gastrointestinal tract are supposed to play key roles in AD pathogenesis. This Review summarizes the potential effects of these SCFAs on β-amyloid (Aß) mediated processes in AD pathogenesis.
  • Methods: We searched literature available with acute key words” Alzheimer disease” Gut-Microbiota” Short chain fatty acids” in PubMed and Web of science, Scopus. All articles were published from 2017 to 2021 and have ethical considerations.
  • Results: It is estimated that approximately 66 million people will suffer from Alzheimer's in 2030 and up from 115 million in 2050. Beta-amyloid (Aß) is thought that initiate neuronal inflammatory processes, which is a hallmark of AD. Amyloid deposition occurs by the accumulation of Aß produced from amyloid precursor protein (APP). This accumulation occurs 15 to 20 years before the onset of AD. Human intestinal microbes, as one of the largest human microbial reservoirs, contain 1014 of the at least 1000 microbial species and (density are above 10 to the power of 12 per mile) that differ in diversity and stability among different individuals. William James and Carl Lange initially explained that there is a two-way connection between the central nervous system and the microbiota, the microbial population in the gastrointestinal tract of organisms, which is traditionally referred to gastric flora and its function is beneficial for host health, which includes: maintaining the integrity of the intestinal barrier, inhibiting the binding of pathogens to the intestinal surface, synthesizing vitamin K, energy salvaging of foods not absorbed by the production of short-chain fatty acids (SCFA). Gut microbiota plays a crucial role in host’s health and disease. Gut microbiota can influence human brain function and behavior. By any alterations in balance of intestinal bacteria (dysbiosis) onset of neurodegenerative process such as AD is inevitable. Gut microbiota is recently considered as a potential factor in AD. Although, their effects on AD pathology remain uncertain. Microbiota metabolites such as SCFA that is fermented from dietary fibers may alter the brain tissue and causes neurodegenerative disorder. Due to hemostasis of hosts, it received most attention in various studies. In this review results showed that the level of SCFAs and subsequently, cognitive ability was decreased due to amyloid deposition. Although, the pathways through which SCFAs may influence psychological functioning, including affective and cognitive processes have not been fully yet elucidated especially in humans. Germ-free (GF) AD mice exhibit a substantially reduced Aß plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice was sufficient to increase the Aß plaque load to levels of conventionally colonized animals. While Aß generation was only mildly affected, we observed strong microglial activation and upregulation of ApoE upon the SCFA supplementation. Taken together, our results demonstrate that microbiota-derived SCFA are the key mediators along the gut-brain axis resulting in increased microglial activation, ApoE upregulation and Aß deposition. Our studies supports the hypothesis that intestinal microbiota may capable protect against AD, in part, by potently inhibiting the generation of select SCFAs, which interfere with the formation of toxic Aß aggregation.
  • Conclusion: This review supports this fact that gut microbiota may help protect against AD progression by generation of SCFAs, which this process interfere with the formation and aggregation of insoluble Aß plaques. Our review highlights how lastly, the development of treatments approachs based on SCFAs can be useful and effective in central nervous system (CNS) disease.
  • Keywords: Neurodegenerative disorder, Alzheimer disease, Gut microbiota, Bacterial metabolites, Short chain fa