The gut microbiome is considered a key determinant in human health. From immune functions to mental well-being, it is often portrayed as a central controller – an invisible organ, deeply influenced by diet and ripe for manipulation. At the forefront of this conception is the idea that what we eat can directly modulate our microbial residents and, through them, our health.

Yet, as attention and claims have grown, so has the gap between evidence and interpretation. While diet is undeniably a modulator of microbial composition, proof for disease causality remains elusive. This article argues that the evidence on the impact of diet on the microbiome is still in its beginning, and despite the focus on unique eating patterns, a wide scope should be used to assess microbiome dietary advice.

How much does diet really influence the microbiome?

In humans, the microbiome is shaped by a wide array of factors: genetics (~8%), metabolic, immune, and neuronal factors, lifestyle, and environmental exposures. Diet has been the most reviewed, with some studies estimating it modulates ~20% of microbial composition, far less than the 50% influence observed in mice. This discrepancy may originate from the type of mouse strain used in the laboratory, as well as the anatomical, physiological, behavioral, and gut microbiome differences that make them more prone to dietary shifts.

So, while mice often offer valuable insights into host-microbiome interactions, it cannot be said with accuracy that their gut microbiome reflects that of humans. Interpretations of diet–induced changes based on these models must be carefully considered when translated to the human context.

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Source: Originally published by Hugenholtz & de Vos., 2017. Reproduced with permission from the author.

Major differences between human and murine intestinal genera. Hugenholtz & de Vos., 2017

In line with this, microbiome research is mainly based on observational studies – with cofounding factors and reverse causation, among other biases – and randomized control trials, almost none of which exceed the one-year mark. This being so, when microbiome composition is assessed after dietary interventions, short-term microbial shifts are registered (sometimes within as little as 24 hours of dietary modification), but many return to baseline within days post-intervention. These findings, while exciting, raise questions about the clinical significance of such rapid and reversible changes: do they have meaningful long-term health implications?

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Source: Originally published by Johnson et al., 2020. Reproduced with permission from the author.

Considerations for participant enrollment and data collection. Johnson et al., 2020.

This concern is critically addressed by Leeming et al. (2019), who highlight how the short duration of most microbiome studies limits their interpretability. They emphasized that microbial fluctuations observed over days or weeks may not represent durable shifts. The study calls for longer-term, human-centered interventions to evaluate whether diet-induced microbial changes are sustained and whether they translate into measurable health outcomes. Without this, conclusions drawn from transient microbiome snapshots risk overstating the impact of dietary interventions.

Building upon this, Johnson et al. (2020) emphasize the critical role of study design in diet-microbiome research. They highlight studies’ limitations, including small sample sizes, lack of control groups, and inadequate consideration of confounding variables like genetics, lifestyle, and environmental factors. This study advocates for more rigorous and standardized study designs, ensuring comprehensive dietary assessments and incorporating multi-omics approaches to better understand the complex interactions between diet, microbiota, and host physiology.

Diet-microbiome relations

Several dietary patterns have become associated with particular microbial signatures. But do these associations prove causality? Or long-term beneficial effects?

Mediterranean diet

The most researched eating pattern, with multiple short-term, randomized controlled trials to back its science. Indeniably associated with numerous health benefits by increasing overall microbial diversity, leading to enhanced short-chain fatty acids (SCFAs) production. Yet, not all evidence can be attributed to microbial metabolism, as Barber et al (2023) highlight in their review; other nonmicrobial-related changes influencing these health benefits must be considered, including geographic location, ethnicity, food availability, lifestyles, and behaviors.

Low-carbohydrate diets

With various degrees of carbohydrate restriction, these eating patterns can vary from moderate to very low-carb ketogenic diets, leading to potential shifts in microbial diversity - ranging from none, high, or low. Nevertheless, several health outcomes, such as weight loss and improvements in cardiometabolic markers, have also been documented. As well as successful treatment of neurological conditions, through the ketone bodies’ metabolic effects and possible impact on the gut microbiome.

Primal or ancestral-style diets

Focused on whole, unprocessed animal-based and seasonal plant foods, these diets try to achieve microbial structures similar to pre-industrial populations. However, documented microbial shifts have not yielded uniform reports, ranging from high to low bacterial diversity. Also, the presence of fiber-degrading SCFA-producing bacteria has been reported. Barone et al (2019) highlighted that “reduced diversity is not necessarily detrimental to the host”. Yet more long-term research is needed; elimination of whole food groups in the everyday diet may need closer examination.

The non-industrialized microbiome restore diet (Nime)

A new diet inspired by the ancient non-industrialized eating habits of indigenous communities in Papua New Guinea, plus Limosilactobacillus reuteri PB-W1 supplementation, was developed. This microbiome-targeted eating pattern has been associated with a low microbial diversity yet a more stable community, as well as being metabolically beneficial. Also, as Fuyong et al. (2025) have interestingly concluded, some bacterial species may be misadapted to high-fiber diets, enabling the adaptiveness of the microbiome. Yet, the microbiome’s plasticity and adaptability have been proposed.

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The Mediterranean diet is characteristic of foods offered to participants during restore periods in interventions.

Across all these patterns, the relationship remains correlative, not causal. Microbial profiles can reflect dietary habits, but the degree to which these changes mediate health outcomes is yet to be established. The different health outcomes described for each of the nutritional patterns above not only have to be reexamined in longer, human-centered studies. They also must be viewed through the lens of curiosity, considering host-resident interactions, to establish the direction of the causality, specific pathways, and consistency of the effects.

Rethinking the evidence

Despite the premise of “food as medicine”, the evidence base for microbiome diet-driven interventions remains thin. Most clinical studies are short-term, focus on microbial composition rather than function, and rarely track long-term health outcomes. Claims that particular diets “heal the microbiome” risk giving false confidence when the underlying science is still evolving.

Overstating diet’s influence on the microbiome also risks shifting public attention away from broader determinants of health. It’s tempting to think that gut microbiome shifts alone can deeply influence health status, but the reality still remains far more complex.

Conclusion

Diet undoubtedly plays a role in shaping the gut microbiome, but its impact is often transient, highly individualized, and insufficiently understood. Current enthusiasm outpaces the data. As microbiome science matures, the field must shift from broad correlations toward precise, long-term, human-centered studies that clarify not just what changes, but why it matters.

Until then, we would do well to temper our excitement with skepticism, and remember that health outcomes emerge from a web of interactions – of which diet and the microbiome are only parts.