Reduction in Gut Bacteria Tied to Elevated AD Biomarkers

Researchers have observed an association between elevated levels of amyloid-beta and tau in the brain and reduced levels of two neuroprotective bacteria in the digestive system, providing more evidence of a connection between gut health and brain health.

"This study reinforces the idea that the buildup of amyloid-beta/tau in middle-aged and cognitively normal individuals are associated with changes in the gut microbiome and function," study investigator Yannick Joel Wadop Ngouongo, PhD, with UT Health San Antonio, Texas, told Medscape Medical News.

The study was presented at the Alzheimer's Association International Conference (AAIC) 2023.

Neuroprotective Effects

Recent research suggests imbalances in gut microbiota may contribute to the pathogenesis of neurological disorders, including Alzheimer's disease (AD). However, whether amyloid-beta and tau deposits, hallmarks of AD, are associated with shifts in gut microbiota composition have not been well studied.

The researchers examined the link between gut microbiome composition and amyloid-beta positron emission tomography (PET) and tau-PET measures in 140 cognitively healthy, middle-aged adults from the Framingham Heart Study (mean age, 56 years; 54% women).

Multivariable analysis revealed a significant association (adjusted P < .001) between amyloid-beta-PET and tau-PET levels and lower levels of Butyricicoccus and Ruminococcus, two types of bacteria that are thought to have anti-inflammatory effects.

Differential abundance analysis revealed a "lower than expected" abundance of these bacteria in the rhinal cortex and inferior temporal cortex in individuals with elevated amyloid-beta-PET and tau-PET measures.

Functional analysis showed that Butyricicoccus and Ruminococcus are butyrate-producing bacteria that also harbor neuroprotective effects.

"These findings begin to reveal more specific connections between our gut and our brain. For example, we believe that the reduction of certain identified bacteria may increase gut permeability and the transport of toxic metabolites in the brain, thus increasing amyloid-beta and tau deposition," Ngouongo said in a statement.

"Clinicians should be aware that gut structure and function are intimately linked to brain health," Ngouongo added. He also noted that it's possible that clinical interventions that restore gut homeostasis could result in less amyloid-beta/tau accumulation and better brain health.

Interconnected Systems

Commenting on the study for Medscape Medical News, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, said the study is noteworthy in that it starts to "define specific gut bacteria that may be associated with increased risk of dementia."

"It’s so interesting to see how impactful gut bacteria might be to cognitive health. And these findings are just beginning to help us unearth some of those details, but we still have a lot to learn," Griffin said.

The Alzheimer's Association is leading a 2-year clinical trial, US Pointer, to examine the impact of behavioral interventions on the gut-brain axis to better understand how engaging in healthier habits impacts microorganisms in the gut and how changes in gut bacteria relate to brain health.

"Our body systems are all interconnected. When one system is malfunctioning, it impacts other systems. When that dysfunction isn’t addressed, it can create a waterfall of consequences for the rest of the body," Heather M. Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said in a conference statement.

Gaining a better understanding of the connection between the digestive system and long-term cognitive function "may uncover novel therapeutic and risk-reduction approaches for Alzheimer’s and other dementias," Snyder noted.

The study was funded by the US National Institutes of Health. Ngouongo, Percy, and Snyder report no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2023. Abstract 74962. Presented July 19, 2023.

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