Is gut microbiome diversity a cause of disease risk or only a marker?

For some diseases, specific gut bacteria are a direct cause of risk, not just a marker.

The strongest evidence for causation comes from Mendelian randomization (MR) studies, which use genetic variants as stand-ins for bacterial levels to see if they directly influence disease. These studies are designed to weed out reverse causation (the disease changing the microbiome) and confounding factors. For epilepsy, one MR study of over 200 bacterial groups found that the class Betaproteobacteria causally increased epilepsy risk by 35.7% (odds ratio 1.357) [1]. This means that people genetically predisposed to have more of these bacteria were significantly more likely to develop epilepsy, suggesting the bacteria play a direct role.

Similarly, for Alzheimer's disease, two large MR analyses found that 16 bacterial taxa were linked to a reduced risk (e.g., Bifidobacterium bifidum lowered risk by about 13%), while 12 taxa, including the class Betaproteobacteria, increased risk by up to 14% [9]. Another study confirmed that the genus Collinsella was a risk factor for Alzheimer's, and its effect was amplified in people carrying the APOE4 gene, a major genetic risk factor for the disease [5]. This interaction between a specific bacterium and a known risk gene strongly points to causation, not just correlation.

For type 2 diabetes, the picture is more nuanced. One MR study found that the family Streptococcaceae was associated with a 17% higher risk of type 2 diabetes in Europeans, but this link was borderline and did not survive strict statistical correction [2]. However, a large observational study of over 2,100 people found that higher microbiome diversity and more butyrate-producing bacteria were strongly associated with lower insulin resistance and a 49% lower odds of type 2 diabetes (odds ratio 0.51 for Clostridiaceae 1) [6]. While observational, this large-scale study controlled for many lifestyle factors, making a causal role for these bacteria plausible.

For other conditions, like Parkinson's disease, microbiome diversity appears to be a marker, not a cause.

Not all diseases show a causal link. A meta-analysis of seven studies on Parkinson's disease, totaling over 1,000 subjects, found no significant difference in gut microbiome alpha-diversity (a measure of the number and evenness of bacterial species) between patients and healthy controls [7]. The same was true for multiple sclerosis across five studies. This suggests that for these neurological disorders, low diversity is not a driving cause but may instead be a consequence of the disease or its treatments (like medication or diet changes).

In contrast, for conditions like heart transplant recovery, low diversity is a powerful marker of risk. A 2025 study of 121 heart transplant recipients found that those who developed a postoperative infection had significantly lower gut microbiome diversity at the time of transplant (p=0.0026) [8]. Their microbiomes were also compositionally different, with expansions of harmful bacteria like Enterococcus and Enterobacterales. Here, low diversity doesn't cause the infection directly, but it signals a weakened gut ecosystem that is vulnerable to pathogen overgrowth, making it a useful clinical marker for identifying high-risk patients.

The role of the microbiome—cause or marker—depends on the specific disease and bacteria involved.

The evidence shows that the question 'cause or marker?' doesn't have a single answer. For some diseases, specific bacteria are clearly causal, as shown by MR studies on epilepsy [1], Alzheimer's [5][9], and to a lesser extent, type 2 diabetes [2][6] and cardiovascular disease [4]. For example, one MR study found that the genus Oxalobacter causally increased the risk of coronary artery disease by 6% [4]. For reproductive endocrine diseases like PCOS and endometriosis, MR studies also identified specific bacteria that causally increased or decreased risk, though the effects were modest [3].

However, for other conditions like Parkinson's disease, the evidence points to the microbiome being a marker rather than a cause [7]. This distinction is crucial because it determines whether interventions like probiotics, fecal transplants, or dietary changes could actually prevent or treat a disease. If the microbiome is a cause, changing it might help. If it's just a marker, treating the underlying disease or its symptoms would be more effective. The takeaway for you is that the gut microbiome is a complex ecosystem, and its relationship with health is highly disease-specific.

About These Sources

This answer is built on 9 peer-reviewed studies — published from 2021 to 2025, 2 from 2024 or later, 7 in Q1 journals, collectively cited 709 times — selected as the most relevant from 9 studies that passed quality screening, drawn from 64 papers retrieved from a database of over 500 million.

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