A collaborative pilot study from the Instituto de Investigación Biomédica de Málaga (IBIMA–Plataforma BIONAND), Virgen de la Victoria University Hospital, the University of Málaga, and partners in Seville, Madrid and Lithuania offers a vivid look at how the Ketogenic (Keto) and Mediterranean (Med) diets shape not only the bodies but also the emotional wellbeing of people with obesity. In exploring weight loss, depression, impulsivity, gut microbiota, and even behavioural changes via microbiota transplants into mice, the researchers uncovered profound differences between the two eating patterns, differences that extend far beyond the scale.
Weight Loss Wins, But Mood Tells Another Story
Thirty-seven adults completed the 3-month hypocaloric intervention, 23 on the Mediterranean diet, and 14 on the Ketogenic diet. Although both groups lost significant weight, the Keto diet delivered the sharper drop, consistent with its aggressive macronutrient profile (only 5% carbohydrates and 65% fat). But when it came to depressive symptoms, the Mediterranean diet decisively outperformed Keto. Participants started with mild depression, yet those on the Med diet saw far greater improvement in Beck Depression Inventory scores. Crucially, mood changes did not correlate with weight loss, suggesting that nutrient quality, rather than kilos shed, played the larger role in emotional health.
Impulsivity Drops Under Keto, Offering a Clue
While the Mediterranean diet lifted mood, the Ketogenic diet significantly reduced impulsivity, especially in the “urgency” dimension, acting rashly when distressed. This reduction may explain why Keto participants adhered more tightly to their regimen and ultimately lost more weight. The contrast between improved impulsivity but lesser mood improvement under Keto paints a complex psychological picture: one diet may support self-control, while the other may better support emotional resilience.
The Gut Microbiome: Where Diets Diverge Dramatically
Stool analyses revealed that both diets reshaped gut bacterial communities, but the Keto diet triggered far more extensive and disruptive microbial shifts. Keto participants experienced losses of beneficial genera such as Bifidobacterium and Incertae Sedis, while showing increases in genera like Aeromonas and Actinomyces. Functional predictions showed 34 microbial pathways altered under Keto, many involved in aromatic compound degradation, compared to just two in the Med group. Meanwhile, the Mediterranean diet boosted Akkermansia, a bacterium consistently linked with metabolic health. These contrasting microbial signatures raised a key question: could these diet-driven bacterial changes influence the brain?
Mice Reveal the Gut–Brain Connection
To probe that question, researchers transplanted participants’ post-diet microbiota into microbiota-depleted mice. The outcome was striking. Mice receiving Keto-derived microbiota displayed anxiety-like behaviours: they moved less, avoided open spaces, hesitated before exploring, and showed more stereotypic actions like head-bobbing and tail flicks. Mice colonised with Mediterranean-diet microbiota behaved more calmly and explored more freely. Microbial sequencing in the animals showed that Keto-recipient mice had reduced diversity, and 20 genera were significantly depleted, suggesting a destabilised gut ecosystem.
Biochemical tests added another layer: Keto-recipient mice exhibited elevated taurine, betaine, and alanine in the brain, with glycine declining. Serum markers also shifted, including higher histidine and methionine and lower succinate. One metabolite, threonine, strongly correlated with exploratory behaviour and reduced freezing, hinting at molecular links between microbial changes and emotional expression. Beneficial genera like Alistipes and Muribaculaceae, associated with healthier behavioural outcomes, were markedly lower in Keto-recipient mice.
A Call for Personalised Diets Beyond Weight Loss
Although the study’s modest sample size and sex imbalance, since the Keto group contained only women, limit broad generalisation, the findings illuminate a powerful truth: diets reshape the gut and brain in distinct ways, and rapid weight loss does not guarantee emotional benefit. For people living with obesity, the Mediterranean diet may offer stronger short-term protection against depressive symptoms, while the Ketogenic diet may bolster self-control but at the potential cost of gut disruptions linked to anxiety-like outcomes in animal models.
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