“A healthy gut is essential for a healthy mind.”
~ Emeran Mayer
Over the last several years, there has been increasing evidence implicating the gut-brain axis in the etiology of neurodegenerative conditions like Alzheimer’s disease. Previous studies utilizing animal models have demonstrated the development of neurodegenerative conditions following the transplantation of the gut microbiome from an affected animal to a previously healthy one, suggesting a strong link between the gastrointestinal tract and the brain.
This week’s study looks at the association between the level of gut inflammation and the spectrum of degenerative neural cognition in Alzheimer’s-type dementia (AD). The human participants were divided into those with clinical AD and those who remain cognitively unimpaired (CU). The latter group was further subdivided into those who had no evidence of amyloid pathology (a diagnostic marker associated with increased risk of developing AD) designated CU Aβ−, and those who were cognitively unimpaired but were at an increased risk of developing Alzheimer’s-type dementia in the future due to the presence of amyloid pathology, designated CU Aβ+.
- The study assessed fecal samples from older adults.
- Samples were obtained from 125 individuals who participated in two prior Alzheimer’s prevention studies.
- The samples were measured for calprotectin, an established marker of intestinal inflammation.
- Elevated calprotectin levels are seen in diseases where there is a compromise of the integrity of the normal gut barrier.
- Calprotectin levels were correlated with clinical diagnosis, participant age, cerebrospinal fluid biomarkers of AD pathology, amyloid burden (measured using 11C-Pittsburgh compound B positron emission tomography (PiB PET)) and performance on cognitive tests measuring executive function and verbal learning and recall.
- Calprotectin levels correlated with increasing age.
- Calprotectin levels were highest in those with amyloid-confirmed Alzheimer’s-type dementia.
- Among those participants with AD, higher calprotectin levels correlated to a greater amyloid burden.
- Among the participants who were cognitively unimpaired (CU), “calprotectin levels were also associated with cerebrospinal fluid markers of AD, and with lower verbal memory function (CU Aβ+) …. Taken together, these findings suggest that intestinal inflammation is linked with brain pathology even in the earliest disease stages. Moreover, intestinal inflammation may exacerbate the progression toward AD.”
The Caveat:
One of the possible mechanisms by which age-related neurodegenerative diseases like Alzheimer’s-type dementia (AD) arise may be related to a form of inflammation known as “inflammaging.” Inflammaging is chronic, continuous, low-grade inflammation associated with age, which may be driven by alterations in the composition of the gut microbiome and by a reduced selectivity of the intestinal barrier. A possible cause of this inflammation may be linked to age-related shifts in the composition of the gut microbiota with the subsequent production of an inflammatory environment that causes degradation of the epithelial barrier. The result is that bacterial components that normally remain in the lumen of the gut instead enter the bloodstream and cause inflammatory havoc, like a black Friday mob of shoppers at the opening of Walmart.
Such a “leaky gut” is also associated with other inflammatory conditions like irritable bowel disease and type II diabetes (T2DM). One of the challenges of deciphering such an association is the chicken and the egg problem: does a “leaky gut” cause diseases like AD and T2DM, or is a “leaky gut” a consequence of having these conditions? It is about remembering that correlation is not necessarily causation.
In the current study, the presence of AD was defined by cerebral aggregation of amyloid beta (Aβ) and phosphorylated tau (pTau) proteins, accompanied by microglial and astrocytic activation and associated neuroinflammation. The study’s findings also suggested that “age increases gut inflammation independently of symptomatic AD.” However, increased gut inflammation was found in those participants who were cognitively unimpaired but amyloid-beta positive (Aβ+). This group scored lowest on memory function, suggesting a preclinical presentation or increased risk of developing AD in the future. The highest level of gut inflammation was found in those with clinical AD.
An important caveat in this study is that although increasing levels of gut inflammation correlated to increasing risk and development of Alzheimer’s-type dementia, the current research “cannot rule out the possibility that development of AD pathology may exacerbate intestinal inflammation.” With that being said, the researchers put forth a hypothesis that it is the increased gut microbiome inflammation that initiates a chronic, continuous, low-level systemic inflammation. This, slowly over time, causes incremental damage, which potentially leads to chronic diseases like diabetes, cardiovascular disease, and neurodegenerative conditions like AD.
The researchers are moving forward to test this hypothesis using a mouse model to see if diet changes associated with increased inflammation can trigger the rodent version of AD. If the forthcoming data suggests that that hypothesis is correct, this opens the door to dietary “interventions that mitigate intestinal inflammation [and] could have a beneficial impact on cognitive function in older adults.” Now, that is, indeed, food for thought!
A Request from Chef Dr. Mike
This week, I am asking a favor: If you enjoy and find the information here and articles like this weekly column at The Center for Food as Medicine helpful, I’ve been nominated to potentially work with RFK Jr. as we share a focus on UPFs. One of the ways they are evaluating potential contributors is through a public voting process. If you know anyone who might help in supporting my efforts and could forward this to help generate a vote for my position, I would appreciate it.
1. If you’d like to see more on my position on ultra-processed foods, please visit my TEDx talk at: https://youtube.com/watch?v=8JBCNFOOSRM…
2. Please go to the website: https://nominees.mahanow.org/t/dr-michael-fenster/11526
3. Click on the “vote” button.
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The Study:
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