The gut microbiota as a link between Alzheimer's disease and obesity

Am J Physiol Gastrointest Liver Physiol. 2024 Dec 1;327(6):G727-G732. doi: 10.1152/ajpgi.00174.2024. Epub 2024 Oct 8.

Abstract

Alzheimer's disease (AD) is a degenerative disease that causes a progressive decline in memory and thinking skills. Over the past few years, diverse studies have shown that there is no single cause of AD; instead, it has been reported that factors such as genetics, lifestyle, and environment contribute to the pathogenesis of the disease. In this sense, it has been shown that obesity during middle age is one of the most prominent modifiable risk factors for AD. Of the multiple potential mechanisms linking obesity and AD, the gut microbiota (GM) has gained increasing attention in recent years. However, the underlying mechanisms that connect the GM with the process of neurodegeneration remain unclear. Through this narrative review, we present a comprehensive understanding of how alterations in the GM of people with obesity may result in systemic inflammation and affect pathways related to the pathogenesis of AD. We conclude with an analysis of the relationship between GM and insulin resistance, a risk factor for AD that is highly prevalent in people with obesity. Understanding the crosstalk between obesity, GM, and the pathogenesis of AD will help to design new strategies aimed at preventing neurodegeneration.

Keywords: Alzheimer’s disease; gut microbiota; gut-brain-axis; microbial metabolites; obesity.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / microbiology
  • Animals
  • Brain-Gut Axis / physiology
  • Gastrointestinal Microbiome* / physiology
  • Humans
  • Inflammation / microbiology
  • Insulin Resistance / physiology
  • Obesity* / complications
  • Obesity* / microbiology
  • Risk Factors