Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly Original paper

What was studied?

This study investigated how a pro-inflammatory gut microbiome signature—specifically the balance between Escherichia/Shigella and Eubacterium rectale—relates to brain amyloidosis, peripheral inflammation, and cognitive impairment. The focus keyphrase gut microbiome amyloidosis association arises directly from the researchers’ aim to determine whether microbiome alterations contribute to Alzheimer’s disease pathology through inflammatory pathways. Using stool qPCR assays and blood cytokine expression profiling, the investigators compared bacterial abundance and inflammatory markers across cognitively impaired elders with amyloid-positive PET scans, amyloid-negative peers, and healthy controls. The study frames gut-driven inflammation as a potential upstream factor in amyloid deposition and neurodegeneration.

Who was studied?

Eighty-three older adults were examined: 40 cognitively impaired amyloid-positive participants (Amy+), 33 cognitively impaired amyloid-negative participants (Amy−), and 10 cognitively healthy controls without amyloid pathology. Participants were drawn from the INDIA-FBP cohort across 18 Italian memory clinics. All provided stool samples and blood for molecular analysis. Groups were similar in age, sex, and BMI, but Amy+ individuals had lower cognitive scores despite comparable MRI markers of neurodegeneration and microvascular changes, underscoring amyloidosis rather than structural differences as the distinguishing biological feature.

Most important findings

The clearest microbiome signal was a robust increase in the pro-inflammatory genus Escherichia/Shigella and a marked decrease in the anti-inflammatory butyrate-producer Eubacterium rectale in Amy+ subjects. Amy+ individuals exhibited more than a seven-fold increase in Escherichia/Shigella compared with Amy− participants and an almost ten-fold reduction in E. rectale relative to controls. Bacteroides fragilis, another anti-inflammatory taxon, was also reduced in Amy+, though less consistently. Parallel to these microbiome shifts, Amy+ participants showed significantly elevated expression of pro-inflammatory cytokines—IL-6, IL-1β, CXCL2, and NLRP3—and decreased IL-10, an anti-inflammatory cytokine. Scatterplots illustrate strong correlations: Escherichia/Shigella abundance is positively associated with IL-1β and NLRP3, while E. rectale showed inverse correlations with these same cytokines. These patterns remained significant even when stratifying by amyloid status, indicating stable microbiome–inflammatory coupling.

Key implications

The findings suggest that a gut-driven inflammatory phenotype may contribute to amyloid pathology in cognitively impaired older adults. The convergence of elevated Escherichia/Shigella, diminished E. rectale, and amplified cytokine responses supports the hypothesis that microbiome imbalance promotes systemic inflammation capable of influencing amyloid deposition. While cross-sectional, this work strengthens a mechanistic model in which microbial dysbiosis helps activate NLRP3 inflammasome pathways, potentially accelerating β-amyloid aggregation. Clinically, the study points to the value of developing microbiome-based biomarkers or interventions that modulate pro- and anti-inflammatory taxa to alter disease trajectory. These results also justify deeper multi-omics investigations into gut–brain immune signaling in Alzheimer’s disease.

Citation

Cattaneo A, Cattane N, Galluzzi S, et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly.Neurobiology of Aging. 2017;49:60–68. doi:10.1016/j.neurobiolaging.2016.08.019