For years, scientists have suspected a potential connection between the ketogenic diet and a calmer immune system, hinting at its possible benefits for individuals battling autoimmune diseases like multiple sclerosis (MS).
Now, groundbreaking research from UC San Francisco is providing compelling evidence to support this theory.
The research team made a remarkable discovery: the keto diet triggers changes in the gut microbiome, leading to the production of two crucial factors that effectively alleviated MS symptoms in mice.
If these findings translate to humans, we could be on the verge of a revolutionary new treatment approach for MS and other autoimmune disorders, using targeted supplements.
The keto diet radically restricts carbohydrates found in foods like bread, pasta, fruits, and sugar, while allowing unrestricted fat consumption. With carbohydrates out of the picture as fuel, the body shifts its energy production to burning fat, generating compounds known as ketone bodies. These ketone bodies serve as an alternative fuel source for cells and possess the unique ability to influence the immune system.
Through their experiments with a mouse model of MS, the researchers observed a striking correlation: mice producing higher levels of a specific ketone body, β-hydroxybutyrate (βHB), exhibited significantly less severe disease progression.
Furthermore, this increased βHB triggered a remarkable response in the gut bacterium Lactobacillus murinus, prompting it to produce a metabolite called indole lactic acid (ILA). This metabolite acts as a powerful brake on the activation of T helper 17 immune cells, which are known culprits in the development of MS and other autoimmune disorders.
“We were incredibly excited to discover that we could shield these mice from inflammatory disease simply by manipulating their diet and supplementing with these key compounds,” enthused Peter Turnbaugh, PhD, a leading researcher from the Benioff Center for Microbiome Medicine at UCSF.
Turnbaugh’s earlier research had demonstrated that when secreted by the gut, βHB acted as a natural countermeasure to excessive immune activation. This led Margaret Alexander, PhD, a postdoctoral scholar in his lab at the time, to investigate the potential of βHB to alleviate MS symptoms in mice.
Their latest study, published in the journal Cell Reports, revealed a crucial link: mice unable to produce βHB in their intestines experienced significantly more severe inflammation when fed a ketogenic diet.
However, when the researchers supplemented their diet with βHB, the mice showed clear signs of improvement.
To pinpoint the precise role of βHB within the gut microbiome, the team isolated bacteria from three distinct groups of mice: those on a ketogenic diet, a high-fat diet, and a high-fat diet supplemented with βHB. They then screened the metabolic byproducts of each group’s unique microbial communities using an immune assay, ultimately identifying a member of the Lactobacillus genus, L. murinus, as the source of the diet’s beneficial effects.
Further analysis using genome sequencing and mass spectrometry confirmed that the isolated L. murinus indeed produced indole lactic acid, a known modulator of immune responses.
In a final compelling experiment, the researchers treated the MS mice directly with either ILA or L. murinus. The results were remarkable: both treatments led to significant improvements in their symptoms.
While these findings represent a significant breakthrough, Turnbaugh urges caution: “The crucial next step is to test the effectiveness of these supplements in human patients with autoimmune disorders.
“It’s crucial to determine how much of these promising results will translate to actual patients,” he emphasizes. “However, I believe these findings offer a ray of hope for developing a more tolerable alternative to the challenging ketogenic diet for those struggling with these conditions.”
Funding: This research was generously supported by the NIH (grants P30 DK063720, R01DK114034, R01HL122593, R01AR074500, R01AT011117, F32AI14745601, K99AI159227, R00AI159227-03, K08HL165106, K08AR073930, R01AG067333, R01DK091538, R01AG069781) and the Damon Runyon Cancer Research Foundation (DRR4216). Peter Turnbaugh is a Chan Zuckerberg Biohub-San Francisco Investigator.
Interview: Shaping the Future of Autoimmune Disease Treatment with the Ketogenic Diet
Time.news Editor: Welcome to the Time.news interview series. Today, we’re privileged to have Dr. Peter Turnbaugh, a leading researcher at the Benioff Center for Microbiome Medicine at UCSF, join us to discuss groundbreaking findings on the ketogenic diet and its potential impact on autoimmune diseases—specifically multiple sclerosis. Welcome, Dr. Turnbaugh!
Dr. Peter Turnbaugh: Thank you for having me! I’m excited to share our findings with you.
Editor: Let’s dive right in. For many, the ketogenic diet is synonymous with weight loss. However, your research indicates it could have significant implications for those suffering from autoimmune diseases. Can you summarize what the ketogenic diet entails?
Dr. Turnbaugh: Absolutely. The ketogenic diet is a high-fat, low-carbohydrate diet that drastically reduces carbohydrate intake. Instead of using glucose derived from carbs as its primary energy source, the body shifts to burning fat, producing compounds known as ketone bodies—especially β-hydroxybutyrate, or βHB. Our research has shown that this metabolic shift can influence the immune system, which is particularly promising for individuals with conditions like multiple sclerosis (MS).
Editor: That brings us to your recent findings. You studied the effects of the ketogenic diet on mice models of MS. What did you discover?
Dr. Turnbaugh: Our research revealed something quite remarkable. Mice that produced higher levels of βHB exhibited significantly less severe disease progression related to MS. This was attributed to the positive changes in their gut microbiome, specifically, a bacterium called Lactobacillus murinus. When stimulated by βHB, this bacterium produced a metabolite called indole lactic acid (ILA), which inhibits the activation of T helper 17 immune cells—known instigators in the development of MS.
Editor: That’s truly fascinating! So, you’re suggesting a dietary approach could be leveraged to alter immune responses effectively. How might this translate to human applications, especially for individuals with autoimmune diseases?
Dr. Turnbaugh: Yes, if the findings in mice translate to humans, we could be looking at a revolutionary treatment strategy. Our next steps involve further validating these results in clinical trials to examine the effects of dietary interventions and supplementation with βHB on MS symptoms in people. By targeting the gut microbiome and utilizing dietary strategies, we could develop more personalized and effective treatments for managing autoimmune diseases.
Editor: The idea of using diet as a treatment is intriguing. However, many people might struggle with adhering to a strict ketogenic diet. Did your study explore alternatives or supplements as a part of this dietary intervention?
Dr. Turnbaugh: That’s a great question. Our initial findings suggest that βHB supplementation could mitigate some inflammation, even when a ketogenic diet isn’t strictly followed. This could serve as an alternative approach for individuals who find the diet challenging. It opens the door to developing targeted supplements that could replicate the benefits of a ketogenic lifestyle without requiring drastic dietary changes.
Editor: Looking ahead, what do you see as the next steps in this research?
Dr. Turnbaugh: We need to conduct further studies to better understand the mechanisms at play and to determine the precise roles of the gut microbiome, βHB, and related metabolites in combating autoimmune diseases. Following that, the goal will be to initiate human clinical trials to explore how we can safely and effectively translate these findings into practice.
Editor: As an expert in microbiomes and their impact on health, what do you believe is the most exciting aspect of this research for the future of autoimmune disease treatment?
Dr. Turnbaugh: I find it incredibly exciting that we may be on the brink of using dietary manipulation and microbiome engineering as therapeutic strategies. If we can harness the power of diet and our own microbiota to modulate immune responses positively, it could transform how we approach not just MS, but a range of autoimmune disorders. The potential for improved quality of life for patients is immense.
Editor: Thank you, Dr. Turnbaugh, for shedding light on this promising avenue of research and its implications. We look forward to seeing how your findings develop and impact those with autoimmune diseases.
Dr. Turnbaugh: Thank you for the opportunity to discuss our work! I appreciate it and hope to see positive changes in the near future.
Editor: That wraps up today’s discussion. Stay tuned for more updates as this research progresses and unfolds!