What is already known
Multiple sclerosis is a long-term autoimmune disease where the immune system attacks the protective covering of nerve fibers in the central nervous system, leading to inflammation, nerve damage, and several neurological symptoms. A ketogenic diet, which is high in fat and low in carbohydrates, can help with autoimmune diseases such as multiple sclerosis by reducing inflammation and altering gut bacteria. But it’s unclear how changes in gut bacteria caused by this diet affect disease.
What this research adds
Working in a mouse model of multiple sclerosis, researchers found that a ketogenic diet boosts the growth of certain gut bacteria, including Lactobacillus murinus. These microbes produce a metabolite called indole-3-lactate (ILA), which has anti-inflammatory properties and can inhibit the activity of immune cells involved in autoimmune responses. The protective effects of the diet were linked to increased levels of a molecule called beta-hydroxybutyrate, or bHB, which modulates immune responses. Giving this molecule to mice mimicked the diet’s effects.
Conclusions
The findings suggest that bHB could be a therapeutic alternative to a ketogenic diet. The results also highlight the protective role of the gut microbiota and its metabolites in autoimmune disease.
Multiple sclerosis is a long-term autoimmune disease where the immune system attacks the protective covering of nerve fibers in the central nervous system, leading to inflammation, nerve damage, and several neurological symptoms. Now, researchers have found that a diet high in fat and low in carbohydrates boosts the growth of certain gut bacteria whose metabolites can inhibit the activity of immune cells involved in autoimmune responses.
The findings, published in Cell Reports, suggest that these metabolites could be a therapeutic alternative to a ketogenic diet. The results also highlight the protective role of the gut microbiota and its products in autoimmune disease.
A high-fat, low-carbohydrate diet, also known as ketogenic diet, has been shown to help with autoimmune diseases such as multiple sclerosis by reducing inflammation and altering gut bacteria. But it’s unclear how changes in gut bacteria caused by the diet affect disease.
To address this question, Margaret Alexander at the University of California, San Francisco, and her colleagues studied a mouse model of multiple sclerosis. The mice had inflammation in the brain and spinal cord caused by the immune system attacking its own tissues.
Diet benefits
The researchers found that feeding mice a ketogenic diet reduced the severity of symptoms. This protective effect was lost in germ-free mice, suggesting that the gut microbiota plays an important role in how the diet influences disease.
The ketogenic diet boosted the growth of certain gut bacteria, including Lactobacillus murinus, that produce a metabolite called indole-3-lactate (ILA). ILA has anti-inflammatory properties and can inhibit the activity of immune cells involved in autoimmune responses.
The protective effects of the diet were linked to increased levels of a molecule called beta-hydroxybutyrate, or bHB, which modulates immune responses, the researchers also found.
Immunomodulatory potential
Further experiments showed that supplementing the ketogenic diet with bHB protected mice from disease, and feeding the animals bHB mimicked the diet’s effects. This result suggests that bHB production in the gut is key for the ketogenic diet’s ability to reduce brain inflammation, the researchers say.
Fecal microbiota transplants further confirmed that the gut microbiota plays a critical role in the protective effects of the diet. Mice that received gut bacteria from other mice fed a ketogenic diet showed less severe disease, while those that received gut bacteria from mice lacking intestinal bHB had worse symptoms.
The findings suggest that targeting gut bacteria and their metabolites could provide easier and more effective treatments for autoimmune diseases, the researchers say. What’s more, they add, “diet alters the immunomodulatory potential of the gut microbiota by shifting host metabolism, emphasizing the utility of taking a more integrative approach to study diet-host-microbiome interactions.”
