Other People with Alzheimer's seem less likely to develop certain types of cancer. A new study hints at why (Sep 2024) Inhibition of colorectal cancer in Alzheimer’s disease is mediated by gut microbiota via induction of inflammatory tolerance

Michael Harrop

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https://www.sciencealert.com/mysterious-link-between-alzheimers-and-cancer-may-finally-be-explained

Among mice with symptoms of Alzheimer's, researchers in China noticed a lower incidence of colorectal cancer than is typical.

The intestinal inflammation among these mice appeared to be suppressed.

When these mice were given a stool transplant from a healthy mouse, however, their rate of cancer in the colon and rectum returned to normal.

When mice were treated with Prevotella bacteria, the gut produced fewer pro-inflammatory immune cells, even when the mouse was exposed to dangerous pathogens.

The reduced inflammatory response probably occurred, in part, because the gut was 'leakier' than is typical, researchers explain, allowing certain microbial byproducts to enter circulation more easily.

When mice were treated with Prevotella-derived compounds, the animals showed cognitive dysfunction and resistance to tumor development in their rectum and colon.

Prevotella bivia, for example, produces high LPS concentrations. These may create a toxic environment that damages dopamine neurons, which play a role in cognitive function and motor function.


https://www.pnas.org/doi/10.1073/pnas.2314337121

Significance​

Our findings provide biological evidence demonstrating the inverse relationship between the incidence of Alzheimer’s disease (AD) and colorectal cancer (CRC). Our results indicate that prestimulation with Prevotella-derived lipopolysaccharides (LPS) can induce intestinal inflammatory tolerance and reduce the incidence of CRC. The regulation of gut microbiota might provide different strategies for the prevention and treatment of AD and CRC.

Abstract​

Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer’s disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT).

AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane–dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella, were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella-derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI.

These data reveal that intestinal Prevotella-derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.
 
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