A modified Mediterranean-style diet enhances brain function via specific gut-microbiome-brain mechanisms
Gwoncheol Park,
Saurabh Kadyan,
Nathaniel Hochuli,
Julie Pollak,
Bo Wang,
Gloria Salazar,
Paramita Chakrabarty,
Philip Efron,
Julia Sheffler,
Ravinder Nagpal
Affiliations
Gwoncheol Park
The Gut Biome Lab, Department of Health, Nutrition, and Food Sciences, College of Education, Health, and Human Science, Florida State University, Tallahassee, FL, USA
Saurabh Kadyan
The Gut Biome Lab, Department of Health, Nutrition, and Food Sciences, College of Education, Health, and Human Science, Florida State University, Tallahassee, FL, USA
Nathaniel Hochuli
The Gut Biome Lab, Department of Health, Nutrition, and Food Sciences, College of Education, Health, and Human Science, Florida State University, Tallahassee, FL, USA
Julie Pollak
Department of Chemistry and Chemical Engineering, Florida Institute of Technology, Melbourne, FL, USA
Bo Wang
Department of Chemistry and Chemical Engineering, Florida Institute of Technology, Melbourne, FL, USA
Gloria Salazar
Department of Health, Nutrition, and Food Sciences, College of Education, Health, and Human Science, Florida State University, Tallahassee, FL, USA
Paramita Chakrabarty
Center for Translational Research in Neurodegenerative Diseases, Department of Neuroscience, University of Florida, Gainesville, FL, USA
Philip Efron
Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA
Julia Sheffler
Center for Translational Behavioral Science, Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, FL, USA
Ravinder Nagpal
The Gut Biome Lab, Department of Health, Nutrition, and Food Sciences, College of Education, Health, and Human Science, Florida State University, Tallahassee, FL, USA
ABSTRACTAlzheimer’s disease (AD) is a debilitating brain disorder with rapidly mounting prevalence worldwide, yet no proven AD cure has been discovered. Using a multi-omics approach in a transgenic AD mouse model, the current study demonstrated the efficacy of a modified Mediterranean-ketogenic diet (MkD) on AD-related neurocognitive pathophysiology and underlying mechanisms related to the gut-microbiome-brain axis. The findings revealed that MkD induces profound shifts in the gut microbiome community and microbial metabolites. Most notably, MkD promoted growth of the Lactobacillus population, resulting in increased bacteria-derived lactate production. We discovered elevated levels of microbiome- and diet-derived metabolites in the serum as well, signaling their influence on the brain. Importantly, these changes in serum metabolites upregulated specific receptors that have neuroprotective effects and induced alternations in neuroinflammatory-associated pathway profiles in hippocampus. Additionally, these metabolites displayed strong favorable co-regulation relationship with gut-brain integrity and inflammatory markers, as well as neurobehavioral outcomes. The findings underscore the ameliorative effects of MkD on AD-related neurological function and the underlying gut-brain communication via modulation of the gut microbiome-metabolome arrays.
