Dietary Sodium Restriction Reprograms Gut Microbial Fermentation and Reduces Host Energy Harvest
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.
Authors
- Venkatakrishna R. Jala (ORCID: https://orcid.org/0000-0002-4206-7305)
- Steven Coon (ORCID: https://orcid.org/0000-0002-4873-2230)
- Saravanan Kolandaivelu (ORCID: https://orcid.org/0000-0002-8552-7850)
- Vazhaikkurichi M. Rajendran (ORCID: https://orcid.org/0000-0002-8999-8721)
- Justin Kupec (ORCID: https://orcid.org/0000-0003-3418-6993)
- Gangqing Hu (ORCID: https://orcid.org/0000-0001-5453-6888)
- Kumaran M. Rajendran
- Geoffrey I. Sandle (ORCID: https://orcid.org/0000-0002-6956-4168)
- Joshua Cornman-Homonoff
- Lei Wang
Institutions
- West Virginia University (US)
- University of Louisville (US)
- St James's University Hospital (GB)
- Fort Peck Community College (US)
- West Virginia University Hospitals (US)
- Yale University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-21
- DOI
- https://doi.org/10.64898/2026.04.20.719706
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health