Alzheimer’s Disease is a brain disorder that gets worse over time. It affects memory, thinking, and how the brain’s “message system” works. Scientists used to think Alzheimer’s was only a brain problem. But now they’ve found that your gut — yes, your stomach and intestines — might play a big role too.
Your gut and brain are constantly talking to each other through something called the gut-brain axis — think of it like a two-way phone line connecting your belly to your brain. If something goes wrong in the gut, it can send “bad signals” to the brain, which could contribute to diseases like Alzheimer’s.
Alzheimer’s Disease is a progressive neurodegenerative disorder characterized by synaptic dysfunction (brain messages don’t get through properly), cognitive decline, and brain alterations. The gut-brain axis, a two directional communication system, plays a role in neurological disorders, including Alzheimer’s Disease.
Recently, evidence indicates supporting a two directional communication between the gut and the brain(1), involving various neuroendocrine, immune, and neuronal interconnected pathways.
Gut microbiota, the community of microorganisms in the intestinal tract, influences brain function, cognition, and behavior. Dysfunction in the gut-brain axis has been implicated in several psychiatric and neurological disorders including Alzheimer’s Disease(2).
Researchers have discovered that alterations in gut microbiota composition, known as dysbiosis, may play a role in the development and progression of Alzheimer’s disease. Differences in gut bacterial communities have been observed between cognitively normal individuals and those with mild cognitive impairment or Alzheimer’s disease, suggesting that microbiome composition and metabolism could influence the onset and progression of the disease. Dysbiosis is generally characterized by reduced microbial diversity, an overgrowth of harmful bacteria that produce toxic metabolites, increased inflammation, and the subsequent disruption of the gut-brain barriers.
In Alzheimer’s disease patients, a decline in beneficial bacterial species, such as Firmicutes—responsible for producing essential metabolites—and Turicibacter, which transports serotonin, have been reported. Conversely, proinflammatory bacterial groups, including Bacteroidetes, Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae, tend to be elevated. Notably, similar gut microbiota changes have been observed in animal models of Alzheimer’s disease.
It is believed that pathogenic bacteria contribute to Alzheimer’s disease by entering the bloodstream, reaching the brain, and triggering a cascade of neuropathological processes. These bacteria and their metabolites may disrupt neurotransmitter production, increase neuroinflammation, and promote β-amyloid (Aβ) accumulation, all of which contribute to cognitive decline. Research indicates that fecal microbiota transplantation from Alzheimer’s disease-affected humans or mice into healthy mice or rats can induce hallmark Alzheimer’s disease features, such as amyloid deposition, cognitive impairment, and a reduced production of new neurons in the hippocampus.
Understanding the complex gut-brain interactions in Alzheimer’s disease has opened avenues for early-stage therapeutic interventions, particularly since the gut is more accessible than the brain. Alzheimer’s disease risk factors can be categorized as nonmodifiable (e.g., age, sex, genetic mutations) and modifiable (e.g., lifestyle, obesity, environmental influences), with gut dysbiosis falling into the latter category. Based on this, researchers are exploring strategies to restore healthy gut microbiota using dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation, with the goal of improving cognitive function and slowing disease progression.
The leading hypothesis linking gut dysbiosis to Alzheimer’s disease suggests that dysbiosis leads to structural, cellular, and functional changes in the gut, including increased intestinal permeability (“leaky gut”), loss of tight junction integrity, reduced mucus secretion, and immune cell activation.
These alterations may allow bacteria to escape from the gut into the bloodstream, initiating a pathological cascade that contributes to Alzheimer’s disease.
However, further research is needed to better characterize these changes and their role in disease progression.
The ability to detect early gut changes through advanced imaging techniques, combined with metagenomic analysis (technique used to study the genetic material (DNA or RNA) directly from the human gut), could provide valuable insights into the pathological events that precede Alzheimer’s disease diagnosis. This approach could not only help identify disease biomarkers but also uncover underlying molecular mechanisms, leading to the development of targeted therapies.
The current research introduces a pioneering application of nano- and micro–X-ray phase-contrast tomography to investigate structural and morphological alterations in the gut at an organ-wide level, without the need for invasive tissue processing such as sectioning or staining(3).
X-ray phase-contrast tomography enables high-resolution 3D imaging of soft biological tissues, which are typically challenging to visualize with conventional X-ray techniques. This method requires minimal sample preparation and does not rely on contrast agents. X-ray phase-contrast tomography is particularly valuable in preclinical neurological research, as it allows for the simultaneous assessment of cell distribution, structural organization, vascular network changes, and other morphological features, facilitating direct comparisons between healthy and diseased states.
For decades, Alzheimer's disease has primarily been viewed as a "brain pathology," with the overproduction and aggregation of β-amyloid being the most widely recognized underlying cause. However, the repeated failure of β-amyloid -centric clinical trials over the years has suggested that by the time Alzheimer's disease is diagnosed, the central nervous system is already so extensively compromised that targeting a single factor is unlikely to be effective. This growing realization has driven efforts to identify early brain and plasma biomarkers to detect the disease at its initial stages and enable timely intervention. More recently, emerging evidence has highlighted the role of peripheral organs, such as the eyes and the gut, in Alzheimer's disease development and the progression of its neuropathology(4).
The gut-brain axis has garnered significant interest due to growing evidence of a close, bidirectional relationship between the gut and the brain. The prevailing theory suggests that dysbiosis—an imbalance in gut microbiota—may contribute to the onset of Alzheimer’s disease.
In contrast, maintaining or restoring a healthy gut microbiota through prebiotics, probiotics, or gut microbiota transplantation is believed to help prevent Alzheimer's disease or slow its progression(5).
A widely accepted mechanism linking gut dysbiosis to an increased risk of Alzheimer’s disease suggests that an overgrowth of harmful bacteria during dysbiosis triggers structural changes in the gut, primarily driven by inflammation. This process involves elevated levels of lipopolysaccharides, pro-inflammatory cytokines, T helper cells, and monocytes, along with increased gut barrier permeability. These changes facilitate the escape of bacteria from the gut into the bloodstream, where they, along with excess inflammatory cytokines, can compromise the blood-brain barrier.
As a result, bacteria may invade the brain, initiating neuroinflammation and leading to abnormal β-amyloid production.
Studies on Alzheimer's disease brains have detected gut bacteria near β-amyloid plaques in the functional tissue of the brain, accompanied by increased pro-inflammatory cytokines in both plasma and brain tissue. Furthermore, gut microbiota transplantation from Alzheimer's disease-affected individuals or mice into healthy mice has been shown to replicate key Alzheimer's disease-related neuropathological features, including cognitive decline, amyloid deposition, and neuroinflammation. These findings suggest a possible connection between gut dysbiosis and the β-amyloid pathway in Alzheimer's disease, offering a potential alternative strategy to modulate brain β-amyloid levels(3).
Currently, most research in the field focuses on gut dysbiosis, microbiota characterization, and bacterial composition.
Omics analyses and metagenomic sequencing, aim to identify associations between changes in microbial composition and neurological dysfunction or neuropathological features. However, limited attention has been given to investigating structural changes in the gut, which could potentially explain or even predict bacterial translocation from the gut lumen and the subsequent risk of disease initiation.
To address this gap, this research investigated the potential of nano- and micro- X-ray phase-contrast tomography to provide detailed three-dimensional imaging of the anatomy and cellular components of the mouse ileum in various Alzheimer’s disease mouse models. Findings from this research demonstrate the remarkable capability of X-ray phase-contrast tomography to visualize the intestinal environment in 3D with exceptional detail and resolution, enabling the detection of even subtle intestinal alterations.
Additionally, at the cellular level, X-ray phase-contrast tomography allows for the collection and analysis of thousands of images, providing comprehensive insights into cellular morphology and distribution in both healthy and diseased states(3).
This research indicates that X-ray phase-contrast tomography is a groundbreaking tool for systematically and comprehensively analyzing the gut. It plays a crucial role in identifying and characterizing gut changes associated with Alzheimer’s disease progression, as well as their relationship with cognitive decline and brain neuropathology.
This research shows that your gut health might be deeply connected to your brain health — especially when it comes to Alzheimer’s. By keeping your gut healthy, you might be protecting your brain at the same time.
And thanks to new imaging tools like X-ray phase-contrast tomography, scientists can now get a clear, detailed picture of what’s happening inside the gut — helping them uncover new ways to diagnose, treat, and maybe even prevent Alzheimer’s disease.
Eat real, nutritious food, exercise every day, and supplement with a probiotic if you need to.
Pro+ FLORA probiotic is a high-potency blend of clinically studied strains designed to support a balanced gut microbiome, reduce harmful bacteria, and strengthen your gut barrier — all crucial steps for protecting both your gut and your brain.
If you want to give your gut the daily support it needs to thrive, grab your bottle of Pro+ FLORA today to fortify and support a healthier gut-brain connection.
References:
1. Jiang C, Li G, Huang P, et al: The Gut Microbiota and Alzheimer's Disease. J Alzheimers Dis 58:1-15, 2017
2. Khan R, Di Gesù CM, Lee J, et al: The contribution of age-related changes in the gut-brain axis to neurological disorders. Gut Microbes 16:2302801, 2024
3. Palermo F, Marrocco N, Dacomo L, et al: Investigating gut alterations in Alzheimer’s disease: In-depth analysis with micro- and nano-3D X-ray phase contrast tomography. Science Advances 11:eadr8511, 2025
4. Casciano F, Zauli E, Celeghini C, et al: Retinal Alterations Predict Early Prodromal Signs of Neurodegenerative Disease. Int J Mol Sci 25, 2024
5. Zhang T, Gao G, Kwok LY, et al: Gut microbiome-targeted therapies for Alzheimer's disease. Gut Microbes 15:2271613, 2023
