The ketogenic diet, characterized by a high fat, very low carbohydrate intake, has garnered significant attention for its potential benefits in weight loss, insulin sensitivity, and seizure reduction. While the mechanisms behind these effects are still being investigated, emerging evidence suggests a crucial role for the gut microbiota. This article delves into the intricate relationship between the keto diet and gut health, exploring its impact on microbial composition, diversity, and function, as well as the potential implications for various health conditions.
What is the Ketogenic Diet?
The ketogenic diet is a dietary regime focused on strongly reducing carbohydrate intake and increasing fat intake, leading to a state of ketosis. Unlike other low-carb diets that emphasize protein, a keto plan centers on fat, which supplies as much as 90% of daily calories. Different protocols exist of ketogenic diets that differ in caloric content and macronutrient percentage which find applications in neurological and metabolic disorders. This metabolic shift forces the body to utilize fat as its primary fuel source, producing ketone bodies as a byproduct. In a daily 2,000-calorie diet, that might look like 165 grams of fat, 40 grams of carbs, and 75 grams of protein.
Variations of the Ketogenic Diet
Several variations of the ketogenic diet exist, each with slightly different macronutrient ratios:
- Classic Ketogenic Diet (cKD): A normocaloric, high-fat, very low-carbohydrate diet, typically composed of a 4:1 ratio of fat (in grams) to protein plus carbohydrates (in grams). It has been used to treat epilepsy in children continuously since 1921.
- Modified Atkins Diet: A variation of the ketogenic diet in which this fat to protein and carbohydrate ratio differs.
- Low Glycemic Index Treatment (LGIT): A variation of the ketogenic diet in which this fat to protein and carbohydrate ratio differs. The ratio of carbohydrate types is specified in the LGIT.
- Medium-Chain Triglyceride (MCT) Diet: A variation of the ketogenic diet in which this fat to protein and carbohydrate ratio differs. The ratio of fat types is specified in the MCT KD
- Very Low-Calorie Ketogenic Diet (VLCKD): A variation of the ketogenic diet that has been recently proposed as an appealing nutritional strategy for obesity management.
The Gut Microbiota: A Key Player in Health
The gut microbiota, a complex community of microorganisms residing in the digestive tract, is increasingly recognized as a crucial "endocrine organ" that influences various aspects of host health, including metabolism, immunity, and brain function. The gut microbiota refers to the bacteria, archaea, and eukaryotes residing in the gastrointestinal tract. The majority colonize the colon, with bacterial numbers estimated at 3.8 x 1013; this review uses the term microbiota to refer specifically to these (31). Microbiota are predominantly from two phyla, Bacteroidetes and Firmicutes, while Actinobacteria, Proteobacteria, and Verrucomicrobia are present in smaller proportions. The principal genera comprise Alistipes, Bacteroides, Faecalibacterium, Bifidobacterium, Eubacterium, Dorea, and Ruminococcus (32). Despite the constancy of these constituents, dramatic differences are present among individuals in terms of relative proportions and species (33). Diet is a major factor shaping the composition and function of the gut microbiota.
The Gut-Brain Axis
SCFAs are often associated with improved metabolic health and also play a pivotal role in the gut-brain axis. Metabolites communicate locally and systemically through metabolic, immune, and neuroendocrine crosstalk with the host (47). Short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are predominant metabolites produced mainly through carbohydrate fermentation by specific species (36, 48). It is well recognized that microbiota are fundamental to human health, with their metabolites playing a key role in modulating disease risk (8, 49). Many metabolites, particularly SCFAs, are beneficial, supporting gastrointestinal integrity and immune system regulation (50, 51).
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Impact of the Keto Diet on the Gut Microbiota
The ketogenic diet can significantly alter the composition and function of the gut microbiota. However, the specific effects can vary depending on the duration of the diet, individual factors, and the specific type of ketogenic diet followed.
Reduced Microbial Diversity
One of the most consistent findings is that the keto diet can lead to a reduction in overall microbial diversity. A reduced alpha diversity is generally associated with worsened metabolic outcomes. This is likely due to the restriction of carbohydrate intake, which limits the availability of fermentable substrates for many gut bacteria.
Changes in Bacterial Abundance
The keto diet can also alter the relative abundance of specific bacterial groups:
- Decrease in Bifidobacteria: Multiple studies have demonstrated a reduction in Bifidobacterium abundance following KD adherence. Bifidobacteria are beneficial bacteria that primarily metabolize carbohydrates, and their decline may be attributed to the low carbohydrate content of the keto diet. Their central fermentation pathway, the fructose-6-phosphoketolase or “bifid shunt,” provides them with an ecological advantage in the presence of carbohydrates, because it produces more energy compared with the fermentation pathways of other bacterial species (87, 88).
- Increase in Akkermansia muciniphila: Increased levels of A. muciniphila, a known short-chain fatty acid (SCFA) producer, is associated with improved metabolic health. Some studies have shown an increase in Akkermansia muciniphila, a bacterium known for its mucin-degrading capabilities and association with improved metabolic health.
- Changes in Firmicutes and Bacteroidetes: The Firmicutes and Bacteroidetes are two dominant phyla in the gut. Some studies have observed a decrease in Firmicutes and an increase in Bacteroidetes with the keto diet.
Altered Short-Chain Fatty Acid (SCFA) Production
SCFAs, such as acetate, propionate, and butyrate, are produced by gut bacteria through the fermentation of dietary fibers and other substrates. These metabolites play a crucial role in maintaining gut health and influencing host metabolism. The keto diet has been shown to reduce total faecal SCFA’s, acetate, and butyrate. KD reduces total faecal SCFA’s, acetate, and butyrate. The reduction in carbohydrate intake on a ketogenic diet can lead to decreased SCFA production. This is because SCFAs are mainly produced from fibres, it can therefore be confusing as to how ketogenic diets can promote the production of SCFA.
Keto Diet and Specific Health Conditions
The interplay between the keto diet and the gut microbiota has implications for various health conditions:
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Epilepsy
One of the first successful implementations of the ketogenic diet were its positive effects on refractory seizures. The gut microbiota is implicated in the seizure-reducing effects of a ketogenic diet. The exact mechanism by which a ketogenic diet contributes to reduced seizure activity remains unknown. However, two mouse studies have shown that gut microbiota composition and function are implicated to be involved in the seizure-reducing effects of a ketogenic diet (6:1 and 3:1). The protective effects of the ketogenic diet were reduced after a broad-spectrum antibiotic course but re-established after recolonizing with bacteria. Multiple studies in epileptic patients and one study in subjects suffering from GLUT1-DS showed that a ketogenic diet intervention (4:1) can indeed alter gut microbial composition.
Weight Loss and Obesity
The ketogenic diet has gained popularity as a method to reduce weight, by inducing a metabolic switch towards fat oxidation which can subsequently reduce hunger by the production of ketone bodies. It is also possible that the gut microbiota are involved in mediating weight loss through a ketogenic diet. Possible mechanisms include increased production of microbial metabolites, like SCFA, that can cross the blood-brain barrier and affect food intake. Another interesting study in both mice and humans found that a ketogenic diet (4:1) led to decreased levels of Bifidobacterium. This decrease was mediated through the increased production of ketone bodies, most importantly beta-hydroxy butyrate, and led to lower levels of intestinal and visceral fat pro-inflammatory Th17 cells. However, weight loss itself can alter the gut microbiota composition. This makes it difficult to disentangle a clear effect of a ketogenic diet versus weight loss itself on the gut microbiota composition and function.
Dyslipidemia
Dyslipidaemia is characterized by lipid abnormalities, i.e., increased total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglyceride plasma levels or decreased high-density lipoprotein (HDL)-cholesterol and is a major risk factor for cardiovascular disease. As described before, a ketogenic diet can lead to weight loss, which has a beneficial impact on blood lipid levels.
Colorectal Cancer (CRC)
The ketogenic diet (KD) has been shown to possess anti-cancer properties in the context of CRC, and several studies have focused on the importance of the restriction of energy intake to slow the growth of rapidly proliferating cells, as well as on anti-cancer signaling through ketone bodies. Cancer progression is accompanied by a state of dysbiosis of the gut microbiome. The anti-cancer effects of the KD are mediated by the gut microbiome. The gut microbiome may affect CRC development either by directly interacting with host cells (attachment, invasion and translocation), or indirectly, through bacterial metabolism (genotoxins, SCFAs and others). The tumor-inhibitory effect of ketogenic diet is mediated by the gut microbiome.
Potential Risks and Considerations
Despite the potential benefits, the ketogenic diet also poses some risks to gut health:
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- Reduced Fiber Intake: The elimination of high-carb foods like fruits, starchy vegetables, grains, and legumes can lead to insufficient fiber intake, increasing the risk of constipation and other digestive disorders.
- Potential for Gut Microbiome Imbalance: The keto diet is often low in fiber and may harm the health of your gut microbiome, potentially increasing inflammation and reducing your concentration of good bacteria.
- Kidney Problems: The kidneys help metabolize protein, and McManus says the keto diet may overload them.
- Fuzzy thinking and mood swings: The brain works best when the energy source is sugar from healthy carbohydrates to function.
Strategies for a Gut-Friendly Keto Diet
To mitigate the potential negative effects on gut health, consider these strategies:
- Include Gut-Friendly Foods: Enjoy a variety of high-fiber, low-carb foods like non-starchy vegetables and low-sugar fruits can help you meet your fiber needs while on a keto diet.
- Consider Probiotic and Prebiotic Supplementation: Probiotics can help replenish beneficial bacteria in the gut, while prebiotics provide fuel for their growth.
- Stay Hydrated: Adequate water intake is essential for maintaining bowel regularity and overall gut health.