Adherence to Life's Essential 8 Enhances Gut Microbiota Diversity and Cognitive Performance

Yannick Wadop Ngouongo¹Jazmyn Muhammad¹Rebecca Bernal¹Claudia L Satizabal^1,2,3,4Alexa Beiser^4,5,6Ramachandran S. Vasan^{10,11,12,5,7,8,9}Ramnik Xavier^13,14,15Tiffany Kautz^1,16Sudha Seshadri^1,17,18,4Jayandra Jung Himali^1,17,2,4,6Bernard Fongang^1,19,2*

• ¹Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX USA, San Antonio, United States
• ²Department of Population Health Sciences, University of Texas Health Science Center at San Antonio, San Antonio, TX USA, San Antonio, United States
• ³Framingham State University, Framingham, Massachusetts, United States
• ⁴Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA USA, Boston, United States
• ⁵Framingham Heart Study (FHS), Framingham, Massachusetts, United States
• ⁶Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, United States
• ⁷Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA USA, Boston, United States
• ⁸Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA USA, Boston, United States
• ⁹Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts, United States
• ¹⁰Boston University’s Center for Computing and Data Sciences, Boston, MA USA, Boston, United States
• ¹¹The University of Texas School of Public Health in San Antonio, San Antonio, TX USA, San Antonio, United States
• ¹²The Long School of Medicine, University of Texas Health Science Center, San Antonio, TX USA, San Antonio, United States
• ¹³Broad Institute of MIT and Harvard, Cambridge, MA, USA., Cambridge, United States
• ¹⁴Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Boston, United States
• ¹⁵Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA., Cambridge, United States
• ¹⁶Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX USA, San Antonio, United States
• ¹⁷Framingham Heart Study, Framingham, MA USA, Boston, United States
• ¹⁸Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, TX USA, San Antonio, United States
• ¹⁹Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX USA, San Antonio, United States

Emerging evidence suggests a complex interplay among cardiovascular health, gut microbiome composition, and cognitive function. Life's Essential 8 (LE8), developed by the American Heart Association, includes vital metrics of cardiovascular health, such as diet, physical activity, nicotine exposure, sleep health, body mass index (BMI), blood glucose, blood lipids, and blood pressure. In this study, we analyzed data from 781 participants in the Framingham Heart Study (FHS) to explore the relationship between LE8 adherence, gut microbiota, and cognitive performance. Multivariable linear regression models and mediation analysis were used to investigate this relationship. Participants with greater adherence to LE8 demonstrated significantly increased gut microbial diversity (α-diversity: Chao1, p = 0.0014; Shannon, p = 0.0071) and distinct microbial compositions (β-diversity: PERMANOVA p = 1e-4). Higher adherence to LE8 was related to an increased abundance of genera Barnesiella and Ruminococcus, while a reduced abundance of Clostridium was associated with higher LE8 adherence. Greater gut microbial diversity (α-diversity: Chao1, p = 0.0012; Shannon, p = 0.0066), and beneficial genera like Oscillospira correlated with better global cognitive scores (GCS). Taxonomic overlap analyses revealed microbial taxa that simultaneously influence both LE8 adherence and cognitive outcomes. Mediation analyses indicated that specific taxa, including Barnesiella and Lentisphaerae, mediated the link between LE8 adherence and cognitive performance. These taxa may serve as key modulators in the gut-brain axis, connecting cardiovascular and brain health. Conversely, higher Clostridium abundance was associated with poorer cognitive performance. This study highlights the significance of comprehensive cardiovascular health metrics in shaping gut microbiota and enhancing cognitive resilience. Our findings underscore the therapeutic potential of targeting gut microbiota to mitigate cognitive decline, warranting further exploration through longitudinal and metagenomic studies.