Summary: New research from UC San Francisco suggests the ketogenic diet may help control multiple sclerosis (MS) by prompting the gut and its microbes to produce immune-modulating compounds. In a controlled mouse study, animals consuming a ketogenic-style regimen produced the ketone body β-hydroxybutyrate (βHB), which worked together with specific gut bacteria to generate metabolites that reduced inflammation and eased MS-like symptoms.
If these findings hold true in humans, they could point to new, supplement-based strategies for treating autoimmune diseases that avoid the strict dietary limitations of the ketogenic diet. Clinical studies in people with autoimmune conditions will be necessary to evaluate safety, effectiveness and practicality.
Key Facts
- The ketogenic diet increased levels of the ketone body βHB in mice, which influenced gut microbial metabolism.
- The gut bacterium Lactobacillus murinus produced indole lactic acid (ILA) in response, a metabolite that suppressed pro-inflammatory T helper 17 cell activity linked to MS.
- Results imply that targeted supplements—either the ketone metabolite or microbe-derived compounds—might offer a more tolerable approach for managing MS symptoms than strict long-term dieting.
Source: UCSF
Background
Researchers have suspected for some time that the ketogenic diet—a high-fat, very low-carbohydrate eating plan—can alter immune responses and potentially benefit inflammatory and autoimmune conditions. The new UCSF study provides mechanistic evidence in a mouse model that links diet-driven host metabolism to changes in the gut microbiome and, ultimately, reduced autoimmune inflammation.
The ketogenic diet shifts the body’s energy source from carbohydrates to fat. In the absence of sufficient carbs, the liver produces ketone bodies such as β-hydroxybutyrate (βHB). These ketones supply energy to cells but also act as signaling molecules that can influence immune function and microbial activity in the gut.
In the study, mice consuming a ketone-rich diet developed higher intestinal levels of βHB and experienced milder disease in an experimental autoimmune encephalomyelitis (EAE) model, commonly used to mimic aspects of multiple sclerosis. Mice genetically unable to produce intestinal βHB developed worse inflammation, while dietary supplementation with βHB improved outcomes.
Microbiome interaction
To identify how βHB affected gut microbes, researchers isolated bacteria from mice fed three diet variants: a ketogenic diet, a high-fat diet, and a high-fat diet supplemented with βHB. By screening the metabolic outputs of each microbial community against immune assays, the team identified beneficial activity associated with bacteria in the Lactobacillus genus, particularly Lactobacillus murinus.
Using genome sequencing and mass spectrometry, the investigators confirmed that the identified L. murinus strain produced indole lactic acid (ILA), a microbial metabolite known to influence immune signaling. ILA reduced activation of T helper 17 (Th17) cells, immune cells that drive inflammation in MS and many autoimmune disorders. When mice with the EAE model were treated directly with ILA or with the L. murinus strain, their clinical symptoms improved.
Implications
These findings demonstrate a diet → host metabolism → microbiome → immune outcome pathway: a ketogenic-style diet raises intestinal βHB, which reshapes the gut microbiota so it generates anti-inflammatory metabolites like ILA that dampen pathogenic immune responses. The study highlights how dietary changes can indirectly alter immune function by changing host metabolites that, in turn, modify the microbiome’s metabolic profile.
Senior author Peter Turnbaugh, PhD, emphasized the potential clinical relevance while urging caution: translating mouse results to people requires further work. Nevertheless, this research opens the possibility of developing supplements—either ketone-based compounds, beneficial bacterial strains, or their metabolites—to provide a more practical, less restrictive option for patients with MS and perhaps other autoimmune diseases.
Study authors and funding
The paper lists multiple contributors from UCSF, the University of Minnesota and Pennsylvania State University, including Margaret Alexander, Vaibhav Upadhyay, Rachel Rock, Lorenzo Ramirez, Kai Trepka, Diego Oreilana, Qi Yan Ang, Caroline Whitty, Jessie Turnbaugh, Darren Dumlao, Renuka Nayak, John C. Newman, Patrycja Puchalska, Peter Crawford, Yuan Tian and Andrew Patterson. Funding sources included several NIH grants and the Damon Runyon Cancer Research Foundation. Peter Turnbaugh is also a Chan Zuckerberg Biohub–San Francisco Investigator.
About this multiple sclerosis research news
Author: Robin Marks
Source: UCSF
Contact: Robin Marks – UCSF
Image: The image is credited to Neuroscience News
Original Research: “A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity” by Peter Turnbaugh et al., published in Cell Reports. The study is reported as open access.
Abstract
A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity
Diet can protect against autoimmune disease, but it is unclear whether these effects arise from direct host metabolism changes or from shifts in the microbiome. Using a ketogenic diet as a model, the researchers dissected these interactions and found that a ketogenic diet rescued the EAE mouse model of multiple sclerosis through microbiota-dependent mechanisms. Supplementing diets with the single KD-dependent host metabolite β-hydroxybutyrate (βHB) also rescued EAE, while mice unable to produce intestinal βHB developed more severe disease. Transplantation of βHB-shaped gut microbiota conferred protection, and specific Lactobacillus sequence variants were linked to reduced Th17 cell activation in vitro. Isolation of an L. murinus strain that protected from EAE and identification of indole lactate as a βHB-enriched metabolite indicate that diet alters the immunomodulatory capacity of the gut microbiota by shifting host metabolism. These results support an integrated approach to studying diet–host–microbiome interactions for autoimmune disease prevention and therapy.