Keto diet improves multiple sclerosis, IBD and arthritis symptoms

Diet plays a pivotal role in influencing autoimmune diseases like multiple sclerosis (MS), inflammatory bowel disease, and rheumatoid arthritis. Despite this, the underlying mechanisms linking diet to disease remain unclear. Recent research highlights the benefits of a high-fat, low-carbohydrate ketogenic diet (KD) in improving MS symptoms in both humans and mice.

This diet induces a metabolic shift, where the body relies on fat for energy, producing compounds called ketone bodies. Among these, β-hydroxybutyrate (βHB) and acetoacetate (AcAc) demonstrate significant effects on immune system regulation.

Ketone bodies impact immune cells by reducing inflammasome activation, altering macrophage metabolism, and enhancing T cell function. Additionally, KDs influence the trillions of microorganisms in the gastrointestinal tract, collectively known as the gut microbiota.

The diet’s ability to shift the gut microbiota’s composition and activity has been shown to reduce intestinal immune activation, thanks in part to βHB’s antimicrobial properties. However, the broader relevance of these microbial shifts in diseases outside the gut, such as MS, remains a key area of study.

Researchers recently explored the effects of KDs on MS using the experimental autoimmune encephalomyelitis (EAE) mouse model. Published in the journal, Cell Reports, this model is widely used to study autoimmune diseases and depends on interactions between the microbiota and the immune system.

Notably, gut microbiota from MS patients has been found to exacerbate EAE symptoms, suggesting shared mechanisms between human MS and the mouse model. These findings provide insights into the complex interactions between diet, the microbiome, and autoimmune diseases.

The study revealed that a microbial community shaped by intestinal production of βHB could protect against EAE. Researchers isolated a strain of Lactobacillus murinus from KD-fed mice that produced a metabolite called indole-3-lactate (ILA).

Both L. murinus and ILA were effective in reducing immune activation and alleviating EAE symptoms. This discovery underscores the potential for targeting microbial metabolism to develop new therapies for autoimmune diseases.

To examine the protective effects of KDs, researchers fed mice either a high-fat diet (HFD) or a KD. The KD consisted of 90.5% fat, 9.5% protein, and no carbohydrates, while the HFD had 75% fat, 15% carbohydrates, and 10% protein. The KD significantly increased circulating levels of βHB compared to the HFD.

Mice were then immunized with a myelin oligodendrocyte glycoprotein peptide to induce EAE. Disease progression was monitored using metrics like disease severity, incidence rate, and immune cell activity.

Mice on the KD exhibited milder disease symptoms compared to those on the HFD. The KD group had a lower incidence rate (40% vs. 60%) and reduced maximum disease scores.

Flow cytometry analyses revealed decreased activation of T cells in the brain and spleen, which are implicated in EAE and MS. These findings confirm that the KD’s impact on systemic immunity extends beyond the gastrointestinal tract.

The role of ketone bodies extends further into their interactions with various immune pathways. βHB dampens inflammatory signals by inhibiting the NLRP3 inflammasome, a protein complex involved in chronic inflammation. This anti-inflammatory action is crucial in controlling autoimmune responses that target tissues like the brain and spinal cord in MS.

Moreover, ketone bodies influence macrophage behavior, shifting them from a pro-inflammatory state to a more regulated, anti-inflammatory role. This dual action on T cells and macrophages underscores the systemic benefits of the KD.

The role of the gut microbiota in modulating disease was further explored by isolating bacteria from mice fed different diets. The microbiomes of KD-fed mice produced metabolic products that suppressed immune activation. Among these, L. murinus emerged as a key player, producing ILA, which inhibited T helper 17 (Th17) cell activation.

Th17 cells are known to drive inflammation in MS and other autoimmune disorders. Supplementing the diet with βHB or ILA replicated the protective effects of the KD, highlighting the significance of these metabolites.

Notably, mice genetically engineered to lack βHB production in the gut showed more severe inflammation when fed a KD. However, their symptoms improved when their diets were supplemented with βHB. This underscores the integral role of ketone bodies in mediating the KD’s benefits through both direct and microbiota-mediated pathways.

The gut microbiota’s influence on autoimmune diseases has been a subject of growing interest. Diet-induced changes in gut microbial composition can alter the production of metabolites like short-chain fatty acids (SCFAs) and indole derivatives.

These molecules interact with host immune cells, influencing inflammation and tissue repair processes. The discovery of ILA as an immunomodulatory metabolite adds a new layer of complexity, linking dietary components to specific microbial actions that benefit systemic health.

The study’s findings offer promising avenues for treating autoimmune diseases. By leveraging the immunomodulatory properties of ketone bodies and gut-derived metabolites, researchers hope to develop more targeted therapies.

According to Peter Turnbaugh, PhD, a leading scientist in the study, “We could protect these mice from inflammatory disease just by putting them on a diet supplemented with these compounds.” This represents a potential alternative to the restrictive nature of KDs, which can be challenging for patients to maintain.

Genome sequencing and mass spectrometry further confirmed that L. murinus’ production of ILA plays a critical role in suppressing immune activation. Treating EAE mice with either ILA or L. murinus significantly improved their symptoms, mirroring the effects of the KD. While these results are promising, Turnbaugh cautions that more research is needed to determine whether these findings will translate to human patients.

The potential for diet-based therapies is particularly compelling given the limitations of current treatments for autoimmune diseases. Existing therapies often involve broad immunosuppression, which can lead to side effects like increased infection risk. A diet-based approach offers a more natural and potentially safer alternative.

By identifying specific dietary components and microbial metabolites that modulate immunity, researchers aim to create supplements that mimic the benefits of a KD without requiring strict adherence to the diet itself.

The study’s insights into diet-host-microbiome interactions have implications beyond MS. The ability to manipulate the gut microbiome through diet and targeted supplementation could pave the way for new treatments for various autoimmune disorders.

As Turnbaugh notes, “These results provide hope for a more tolerable alternative for patients than a restrictive diet.” Future research will focus on translating these findings to clinical settings and exploring their applicability to other diseases.

Emerging evidence suggests that other autoimmune conditions, such as rheumatoid arthritis and inflammatory bowel disease, may similarly benefit from microbiota-targeted therapies. The shared mechanisms between these diseases highlight the gut microbiome’s central role in immune regulation. By harnessing the power of dietary interventions, scientists are beginning to uncover a new frontier in personalized medicine.

Furthermore, the implications of this research extend to neurological disorders beyond autoimmune diseases. The gut-brain axis—a bidirectional communication pathway between the gut and the central nervous system—is increasingly recognized as a key player in conditions like Parkinson’s disease and Alzheimer’s disease. The ability of dietary components to influence this axis through microbiota-mediated pathways offers exciting possibilities for future therapeutic strategies.

By deepening our understanding of how diet influences the immune system through both direct and microbiota-mediated mechanisms, scientists are uncovering new strategies for managing autoimmune diseases.

These discoveries highlight the potential of integrative approaches that combine dietary interventions with microbiome modulation to improve patient outcomes.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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