Dietary Sodium Restriction Reprograms Gut Microbial Fermentation and Reduces Host Energy Harvest

ABSTRACT Diet is a major determinant of gut microbiome structure and function, yet the role of dietary electrolytes—particularly sodium—remains poorly defined. Here, we identify dietary sodium availability as a key regulator of gut microbial fermentation and host energy harvest. Using a controlled sodium-sufficient versus sodium-deprived dietary intervention in rats, we integrated shotgun metagenomic sequencing, functional pathway analysis, targeted short-chain fatty acid (SCFA) quantification, and host physiological phenotyping. Sodium deprivation induced a coordinated restructuring of the gut microbiome, characterized by depletion of classical saccharolytic Firmicutes, including multiple Lactobacillus species, and enrichment of stress-tolerant, metabolically flexible taxa. Functional profiling revealed a shift away from growth-associated metabolic programs toward stress-adaptive and nutrient-scavenging pathways. Consistent with these changes, fecal concentrations of key SCFAs—including acetate, butyrate, hexanoate, and valerate—were significantly reduced, indicating impaired microbial fermentative capacity. These microbiome-level alterations translated into measurable host phenotypes, including reduced cecal mass and attenuated weight gain, consistent with decreased microbial energy harvest. Together, these findings establish a functional link between luminal sodium availability, microbial metabolic efficiency, and host energy balance, extending the framework of diet–microbiome interactions beyond macronutrients to include dietary electrolytes. This work identifies sodium as a previously underappreciated ecological constraint shaping gut microbial metabolism and suggests that modulation of dietary sodium intake may influence host metabolic outcomes through microbiome-mediated mechanisms. Competing Interest Statement The authors have declared no competing interest. Footnotes kumaran.rajendran{at}westernu.edu; kolandaivelus{at}hsc.wvu.edu, SCoon{at}fpcc.edu, jkupec{at}hsc.wvu.edu; lei.wang1{at}hsc.wvu.edu; michael.hu{at}hsc.wvu.edu, venkatakrishna.jala{at}louisville.edu Conflicts of interest: The authors disclose no conflicts. https://dataview.ncbi.nlm.nih.gov/object/PRJNA1401895?reviewer=ulodnmlnnnfer8nu8cgg514oan