Multiomic Analysis of the Gut Microbiome and Serum Metabolome in Response to a Low-Carbohydrate, High-Protein Diet in Individuals With Spinal Cord Injury.

Background: Dietary interventions play a significant role in preventing and managing cardiometabolic diseases partly through their impact on the gut microbiome and circulating metabolites. Objectives: To assess the impact of an 8-week low-carbohydrate, high-protein (LC/HP) diet on gut microbiome composition, function, and serum metabolome in individuals with spinal cord injury (SCI). Methods: Twenty-four adults with chronic SCI were randomized into an LC/HP diet or a control group for 8 weeks. Stool and fasting serum samples were collected at baseline and week 8. The gut microbiome composition and metabolic potential were determined using metagenomic sequencing, while serum metabolome was assessed through untargeted liquid chromatography-tandem mass spectrometry. Statistical analyses focused on diet and time interaction effects, using R (version 4.1.0). Results: A trend for increased alpha diversity (Gini-Simpson, P = .09) in the diet group indicated a more evenly distributed microbial community. Compared to the control group, several microbiome species (e.g., Fusicatenibacter saccharivorans, Eubacterium siraeum) that are implicated with better intestinal health and reduced inflammation increased, while other species (e.g., Hungatella hathewayi, Clostridium symbiosum) that are associated with colorectal cancer risk decreased in the diet group. Microbial metabolic pathways related to amino acid and purine nucleotides were altered. Increased tryptophan betaine and decreased 8-hydroxy-deoxyguanosine were observed in the serum in the diet group (P interaction < .05), indicating compliance and reduced oxidative stress, respectively. Conclusion: Adopting an LC/HP diet resulted in favorable gut microbiome and metabolome adaptations that may reduce the risk for cardiometabolic disease and colorectal cancer in individuals with SCI.