Approximately 1 in 9 people over the age of 65 has Alzheimer’s dementia, contributing to an estimated 50 million people worldwide living with dementia, the majority of whom have Alzheimer’s disease. This makes it one of the biggest global health and socioeconomic challenges faced today. Alzheimer’s disease is becoming more prevalent, driven primarily by ageing populations and increased life expectancy. This has led to modifiable risk factors increasingly being explored. A proposed hypothesis suggests that ultra-processed food (UPF) may influence neurodegenerative processes through an intermediate, the gut microbiome. Diet-induced alterations to the composition of the microbiome have been linked to changes in systemic metabolic and inflammatory pathways, which may influence neuroinflammatory processes implicated in Alzheimer’s disease pathology. In recent years, emerging cohort studies have begun to investigate possible associations between cognitive decline, an increased risk of developing Alzheimer’s disease and ultra-processed food consumption. However, the current evidence base remains limited, with very few studies directly examining this relationship. This raises the question, are we seeing a small evidence base because the effect is weak, or because of the complexity of studying these interactions?
A key assumption underlying this proposed pathway is that ultra-processed diets exert systemic biological effects on metabolic and inflammatory health. Evidence for this can be seen in a scoping review of 24 studies analysing the relationship between UPF consumption and systemic inflammatory biomarkers, which demonstrated that the increased consumption of UPF was associated with increased C-reactive protein (CRP), a known marker of inflammation measurable using a blood sample. Additives in UPF, such as preservatives, emulsifiers, and colourants, may contribute to the stimulation of an inflammatory immune response through perturbing gut flora and increasing intestinal permeability. Another potential mechanism is that the dietary composition influences metabolic state; for example, excessive intake of saturated fats can shift the gut microbiota towards a more inflammatory state (Jacopo Ciaffi et al., 2025). These effects are significant because both mechanisms cause chronic low-grade inflammation within the gut, which is linked to neuroinflammation. However, as a scoping review, this only collects and summarises studies and is limited in how deep it can go into the analysis of these studies. The studies show correlation; they show that increased consumption of UPF does increase CRP, but they cannot prove causation. There may also be confounding variables, for example, frequency and intensity of exercise or socioeconomic status. Overall, it is likely that there is an association between UPF and systemic inflammation, but the causation is unclear; this is plausible but not fully established.
The proposed link between systemic inflammation and neuroinflammation is through the gut. The gut microbiome contains trillions of microorganisms that regulate both the immune system and metabolism. Homeostasis is the term used to describe the state of internal conditions that are kept within a specific range for the body to function (Libretti and Puckett, 2023). An imbalance in these optimal conditions is called dysbiosis, a condition likely caused by poor diet, e.g. UPFs, low fibre, high fat. This causes increased intestinal permeability or “leaky gut”, which means bacterial products, e.g. toxins like lipopolysaccharide (LPS) and other inflammatory products, can enter the bloodstream, causing chronic low-grade inflammation. Normally, the brain is protected from toxins such as LPS or CRP by the blood-brain barrier, a selective semipermeable membrane between the blood and the interstitium of the brain, allowing cerebral blood vessels to regulate the movement of molecules and ions between the blood and the brain (Dotiwala, McCausland and Samra, 2019). However, there is growing evidence that inflammation can weaken the blood-brain barrier and allow inflammatory signals to affect the brain. As a result of this, the brain is exposed to inflammatory mediators, which may contribute to neuroinflammation. However, much of this evidence is derived from both animal studies and mechanistic models, giving this limited external validity as to how this pathway works within human individuals. Furthermore, the complexity of the human microbiome is extreme, and it varies massively between individuals. This, therefore, cannot prove causation and isolate diet as the only cause.
There is growing evidence to support the role of the gut microbiome in Alzheimer’s disease, with studies suggesting that microbial composition differs between affected individuals and healthy controls. Studies show that Alzheimer’s patients often have reduced microbial diversity, more pro-inflammatory bacteria, and fewer anti-inflammatory bacteria, meaning their gut environment is more inflammatory. This can be caused by multiple pathways, notable ones being one, dysbiosis, more inflammatory mediators circulating in the blood, and two, an amyloid connection. Some gut bacteria produce amyloid-like proteins that may potentially influence amyloid-beta deposition in the brain. Pathway one likely contributes to inflammation, which activates the brain’s microglia, immune cells living only in the brain, and chronic activation of this pathway leads to neuronal damage. Alzheimer’s disease may disrupt communication, resulting in widespread loss of brain function as many neurons stop working properly and eventually die (National Institute on Ageing, 2024). The question here is, are microbiome changes causing Alzheimer’s? or does Alzheimer’s change the microbiome? And the answer, we don’t know. The evidence base surrounding this is limited; many studies are small and cross-sectional, showing only a snapshot in time. This means we cannot yet prove that this is causation as opposed to correlation.
Despite the plausibility of the proposed biological pathway, significant limitations remain in establishing a direct relationship between ultra-processed diets, the gut microbiome and Alzheimer’s disease. There are still confounding variables, however, as UPF consumption is linked to other factors such as physical activity, socioeconomic status and overall diet quality, it is hard to isolate UPF as the cause. There are also measurement issues within the studies. Often, diet is self-reported, creating a sense of unreliability within the data. The microbiome is also highly variable person to person and is hard to measure consistently. These studies are mainly short-term, and Alzheimer’s is a disease which develops over decades. The short-term factor makes it hard to link cause to effect. There is also a possibility that we are looking at this from the wrong angle, and it is that early Alzheimer’s may change diet and therefore microbiome. Taken together, these limitations highlight that while the proposed pathway is plausible and supported by emerging evidence, it remains difficult to establish a clear relationship. Therefore, the extent to which ultra-processed diets influence Alzheimer’s disease risk through gut microbiome and neuroinflammatory mechanisms is currently limited, with the evidence suggesting an indirect and not fully established link.
In conclusion, the evidence suggests that ultra-processed diets may be associated with Alzheimer’s disease risk through systemic inflammatory intermediates and gut microbiome disruption, which are plausible mechanisms linked to neuroinflammation. However, while supportive evidence such as increased inflammatory biomarkers (e.g. CRP) and observational differences between microbiome composition in Alzheimer’s patients vs healthy patients, the evidence remains based on associations. Overall, the current research basis is limited by reliance on observational and cross-sectional studies, as well as there being confounding factors. In addition, the developmental timescale and the possibility of reverse causation further weaken this statement. Therefore, the extent to which ultra-processed diets influence Alzheimer’s disease risk through the gut microbiome and neuroinflammatory mechanisms is plausible but not yet established, representing an emerging but still uncertain area of research.
C. Kemmish, Lower Sixth
