Study uncovers gut microbial patterns linked to Alzheimer’s disease in Puerto Rico - even showing up long before diagnosis

A new investigation into the links between Alzheimer’s disease and the gut microbiome in Puerto Rico has found specific gut microbial patterns associated with cognitive decline, disease severity and genetic risk factors.

The study by researchers at the University of Puerto Rico also found that some cognitively healthy participants and caregivers of the patients also showed signs of cognitive decline and the associated microbiome alterations - suggesting that subtle changes may occur earlier than expected.

Dr Filipa Godoy-Vitorino from the Department of Microbiology at the University of Puerto Rico Medical Sciences Campus, the AMI Global Ambassador for Puerto Rico, is involved in the study - the first to investigate the relationship between the gut microbiome and Alzheimer’s disease in Puerto Rican older adults.

“We discovered that specific gut microbial patterns are associated with cognitive decline, dementia severity, and genetic risk factors such as the ApoE4 allele, highlighting the importance of population-specific microbiome research in Alzheimer’s disease,” she revealed.

Leading cause of death

Alzheimer’s disease is one of the leading causes of death in Puerto Rico and is expected to increase dramatically as the population ages. Hispanic populations, including Puerto Ricans, remain underrepresented in microbiome and neurodegenerative disease research.

The team wanted to understand whether changes in the gut microbiome could be linked to cognitive impairment and Alzheimer’s disease progression in Puerto Ricans, and whether genetic risk factors such as ApoE4 influence these microbial communities. The long-term goal is to identify microbial signatures in gut and oral cavity that may help improve prevention, diagnosis, and future therapeutic strategies.

They recruited 100 Puerto Rican participants between the ages of 55 and 94, including 50 individuals diagnosed with Alzheimer’s disease and 50 cognitively healthy controls. Participants underwent neurological and cognitive evaluations, including the Montreal Cognitive Assessment (MoCA) and Clinical Dementia Rating (CDR), along with ApoE genetic testing. Stool samples were collected to analyze the gut microbiome using 16S rRNA sequencing and advanced bioinformatics tools.

Microbial patterns

“Although we did not observe major differences in overall microbial diversity between Alzheimer’s patients and controls (we acknowledge a relatively low cohort due to the difficulty in recruiting these specific patients), we identified subtle but important microbial shifts associated with disease severity and cognition,” said Dr Godoy-Vitorino.

“Individuals with Alzheimer’s disease showed increased levels of bacteria such as Bifidobacterium, Streptococcus, and Eggerthella, while cognitively healthy individuals had higher levels of beneficial butyrate-producing bacteria such as Faecalibacterium, Blautia, and Bacteroides.

“We also found that lower microbial diversity correlated with greater cognitive impairment, especially in individuals with moderate and severe dementia. Additionally, participants carrying the ApoE4 genetic risk factor showed depletion of bacteria linked to anti-inflammatory and gut-protective functions.”

Subtle changes

One surprising finding was that, based on clinical evaluations, many cognitively “healthy” participants - mostly sons and daughters or caregivers who came with the patients - still showed lower cognitive scores in the MoCA assessment and microbiome alterations associated with cognitive decline similar to those with AD.

“This suggests that subtle cognitive impairment and microbial changes may occur earlier than expected. We were also surprised by how strongly certain microbial patterns correlated with dementia severity and ApoE4 status despite relatively small overall differences in diversity between groups.

“These findings reinforce the idea that microbiome composition, rather than simply diversity alone, may play an important role in Alzheimer’s disease,” said Dr Godoy-Vitorino.

The findings support growing evidence that the gut microbiome may play an important role in neuroinflammation and cognitive decline associated with Alzheimer’s disease. Better understanding these microbial changes could help guide future prevention and treatment strategies, including dietary interventions, probiotics, microbiome restoration therapies, and personalized medicine approaches tailored to an individual’s microbial profile.

Urgent need

Importantly, this study highlights the urgent need for more microbiome research in Hispanic and Caribbean populations, which remain significantly underrepresented in large microbiome datasets despite known differences in genetics, diet, lifestyle, and environmental exposures. Population-specific studies are critical to ensure that future diagnostics and therapies are effective, inclusive, and equitable across diverse communities.

“Our work also underscores the importance of nutrition and public health education. Puerto Ricans rank among the lowest in fruit and vegetable consumption across U.S. territories, which may negatively impact gut microbial diversity and overall health,” said Dr Godoy-Vitorino.

“Increasing awareness about the importance of dietary fiber and healthier eating habits could become an important strategy for improving microbiome health and potentially reducing chronic inflammatory and neurodegenerative disease risk in Hispanic populations.”

Next steps

Future studies should follow patients over time to better understand how microbiome changes evolve during Alzheimer’s disease progression and whether microbial alterations contribute directly to cognitive decline. Larger longitudinal studies integrating diet, lifestyle, inflammation markers, metabolomics, and brain imaging will be important, she said.

Meanwhile, the team is currently expanding its research to investigate the relationship between oral microbiota dynamics and Alzheimer’s disease. Researchers are also collaborating with dentists and oral health researchers to study how microbial biofilms and periodontitis may contribute to neuroinflammation and cognitive decline. These efforts aim to better understand how both the gut and oral microbiomes interact in the progression of Alzheimer’s disease and related dementias.

The study, published in Scientific Reports, was co-led by PI Dr. Vanessa Sepúlveda-Rivera from the Internal Medicine Department and Co-PI Dr. Filipa Godoy-Vitorino from the Department of Microbiology at the University of Puerto Rico Medical Sciences Campus. The project involved a multidisciplinary team of clinicians, microbiologists, psychologists, students, and computational researchers. The study was supported by the National Institutes of Health, including the National Institute of General Medical Sciences Alliance program, the HiREC Endowment Program focused on Hispanic health disparities research and partial support from the RCMI center.